Immunisation, Shigella Infection
Conditions
Keywords
Challenge, Double-blind, Efficacy, Healthy Adults, Immunogenicity, Live-attenuated Shigella sonnei Vaccine, Phase 2 Trial, Placebo-controlled, Protective efficacy, Randomized, Reactogenicity, Safety, Shigella sonnei 53G Challenge, WRSs2
Brief summary
This is a trial to evaluate the safety, reactogenicity, immunogenicity and efficacy of a 10\^6 cfu dose of an oral live-attenuated S. sonnei vaccine candidate, WRSs2, in up to 120 healthy males and non-pregnant females aged 18-49, inclusive. This is a two-phase study, an outpatient WRSs2 vaccination phase and an inpatient S. sonnei 53G challenge phase. After the initiation of the study, two participants had Grade 3 diarrhea and/or vomiting in the days following vaccination. The vaccination dose was reduced to 5X10\^5, enrollment was changed to 2 arms and randomized 2:1 (vaccine: placebo). Participants with morbid obesity were excluded and weight loss medications prohibited. The Primary Objective of this study is to estimate combined vaccine efficacy of 2 doses of WRSs2 (10\^6 cfu or 5X10\^5 cfu) in preventing shigellosis, following challenge with S. sonnei strain 53G.
Detailed description
This is a double-blind, placebo controlled, randomized study to test the safety, reactogenicity, immunogenicity and efficacy of up to a 10\^6 cfu dose of an oral live-attenuated S. sonnei vaccine (WRSs2) to protect against shigellosis after a targeted oral challenge with S. sonnei 53G, a virulent strain of S. sonnei. Up to 120 subjects, healthy males and non-pregnant females aged 18-49, will be enrolled and randomized in this study. Using the 10\^6 CFU dose, subjects were randomized 1:1:1 into one of three vaccination arms to receive 2 doses of study agent 28 days apart. Arm 1 received 2 doses of WRSs2, Arm 2 received placebo followed by WRSs2 and Arm 3 received 2 doses of placebo. Twenty-eight (+2) days after the second dose of study agent, subjects were admitted to the inpatient unit and given an oral challenge of approximately 1500 cfu of 53G. The goal was to have 90 subjects (30 per arm) receive a challenge dose of 53G. The study duration is approximately 24 months with subject participation duration approximately 8 months. After the initiation of the study, two participants had Grade 3 diarrhea and/or vomiting in the days following vaccination. The vaccination dose was reduced to 5X10\^5, enrollment was changed to 2 arms and randomized 2:1 (vaccine: placebo). Participants with morbid obesity were excluded and weight loss medications prohibited. The Primary Objective of this study is to estimate combined vaccine efficacy of 2 doses of WRSs2 (10\^6 cfu or 5X10\^5 cfu) in preventing shigellosis, following challenge with S. sonnei strain 53G. The Secondary Objectives are to:1) Estimate vaccine efficacy of 1 dose of 10\^6 cfu, 2 doses of 10\^6 cfu, and 2 doses of 5x10\^5 cfu of WRSs2 in preventing shigellosis following challenge with S. sonnei strain 53G. 2) Evaluate the safety of WRSs2; 3) Evaluate immune responses following vaccination (immunogenicity) with WRSs2 and after challenge with S. sonnei strain 53G by serum anti-LPS and anti-Invaplex IgG and IgA by ELISA; 4) Determine fecal shedding of S. sonnei after WRSs2 vaccination and 53G challenge by qualitative stool culture.
Interventions
OTHERPlacebo
0.9% Sterile Normal Saline, USP
BIOLOGICALShigella sonnei strain 53G
1.5 x 10\^3 Colony Forming Units (cfu) Shigella sonnei 53G, a virulent strain of wildtype Shigella sonnei
BIOLOGICALWRSs2
10\^6 Colony Forming Units (cfu) dose of an oral live-attenuated Shigella sonnei vaccine candidate derived from a virulent S. sonnei strain Moseley (WRSs2)-a live, attenuated vaccine that has been manufactured under cGMP conditions at the WRAIR PBF
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provide informed consent prior to initiation of any study procedures. 2. Are able to understand and comply with planned study procedures and be available for all study visits. 3. Is 18-49 years of age inclusive and in sufficiently good health\* to be safely enrolled in this study as determined by medical history, medication use, and abbreviated physical exam. \*Good health is defined by the absence of any exclusionary medical conditions. If the subject has another current, ongoing medical condition, the condition cannot meet any of the following criteria: 1) first diagnosed within 3 months of enrollment; 2) is worsening in terms of clinical outcome in last 6 months; or 3) involves need for medication that may pose a risk to subject's safety or impede assessment of adverse events or immunogenicity if they participate in the study. Topical, nasal, and inhaled medications (with the exception of inhaled corticosteroids as outlined in the Subject
Exclusion criteria
, herbals, vitamins, and supplements are permitted. 4. Oral temperature is less than 100.4 degrees Fahrenheit. 5. Pulse is 50 to 100 beats per minute (bpm), inclusive. 6. Systolic blood pressure is 90 to 140 mmHg, inclusive. 7. Diastolic blood pressure is 55 to 90 mmHg, inclusive. 8. Females of childbearing potential\*\* may enroll if subject has practiced adequate contraception\*\*\* = / \> 30 days prior to enrollment and agrees to continue adequate contraception for the entire study. \*\*Child-bearing potential is defined as not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or \<1 year of the last menses if menopausal. \*\*\*Adequate contraception includes; non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject enrollment, barrier methods such as condoms or diaphragms with spermicide, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables, or oral contraceptives ("the pill"). 9. Females of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to enrollment. 10. Drug screen for opiates is negative. 11. BMI (Body Mass Index) between 18 and 40kg/m\^2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Participants With Shigellosis Following Challenge With Shigella Sonnei 53G Through Day 63 in the Pooled Group of Participants Receiving Two Doses of 10^6 Cfu or 5x10^5 Cfu of WRSs2 Compared to Participants Receiving Two Doses of Placebo. | Day 57 through Day 63 | Following study vaccination on Days 1 and 29, participants were admitted to an inpatient facility and challenged with Shigella sonnei strain 53G on Day 57. From challenge through Day 63, all stools passed by challenged participants were graded for consistency, all grade 3-5\* stools were visually assessed for gross blood, and all gross blood-containing stools were confirmed via hemoccult test. A blinded endpoint review committee of independent Shigella experts determined whether shigellosis occurred for each participant based on number, weight, consistency, and hemoccult-positive status of stools, along with the presence of additional enteric symptoms. \*Stool consistency was graded according to the following scale: 1 = Normal stool (best outcome); 2 = Soft stool; 3 = Loose stool; 4 = Watery stool; 5 = Rice water (worst outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Participants With Shigellosis Following Challenge With S. Sonnei 53G Through Day 63 in Participants Receiving 1 Dose of 10^6 Cfu, 2 Doses of 10^6 Cfu, or 2 Doses of 5x10^5 Cfu of WRSs2 Compared to Those Receiving Two Doses of Placebo. | Day 57 through Day 65 | Following study vaccination on Days 1 and 29, participants were admitted to an inpatient facility and challenged with Shigella sonnei strain 53G on Day 57. From challenge through Day 63, all stools passed by challenged participants were graded for consistency, all grade 3-5\* stools were visually assessed for gross blood, and all gross blood-containing stools were confirmed via hemoccult test. A blinded endpoint review committee of independent Shigella experts determined whether shigellosis occurred for each participant based on number, weight, consistency, and hemoccult-positive status of stools, along with the presence of additional enteric symptoms. \*Stool consistency was graded according to the following scale: 1 = Normal stool (best outcome); 2 = Soft stool; 3 = Loose stool; 4 = Watery stool; 5 = Rice water (worst outcome). |
| Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination. | Day 1 through Day 8, Day 29 through Day 36 | Systemic solicited adverse events (AEs) were collected pre-vaccination, 90 minutes post-vaccination, and then daily for 7 days after each vaccination using a memory aid and graded on a scale of 0 (none), 1 (mild), 2 (moderate) and 3 (severe). Systemic events include fever, headache, arthralgia, nausea, pain/abdominal cramps, fatigue/malaise, myalgia, anorexia/loss of appetite, chills, vomiting, and diarrhea. |
| Number and Percentage of Participants With Vaccine-related Unsolicited AEs Through 28 Days Post Last Vaccination | Day 1 through Day 57 | ICH E6 defines an AE as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product regardless of its causal relationship to the study treatment. FDA defines an AE as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. The occurrence of an AE may come to the attention of study personnel during study visits and interviews of a study recipient presenting for medical care, or upon review by a study monitor. An AE is considered related if there is a reasonable possibility that the study product caused the AE. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the AE. |
| Number and Percentage of Participants With SAEs Through Study Day 180 or Until Resolution or Stabilization Even if This Extends Beyond the Study-reporting Period. | Day 1 through Day 180 | An AE or suspected adverse reaction is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: * Death * A life-threatening AE * Inpatient hospitalization or prolongation of existing hospitalization * A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions * A congenital anomaly/birth defect * Important medical events that may not result in death, be life-threatening, or require hospitalizations may be considered serious when, based upon appropriate medical judgment they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. |
| Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 15, Day 29, Day 43, and Day 56 | Serum was collected pre-challenge at Day 1 (pre-dose 1), Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgG antibody response against LPS (a Shigella sonnei antigen) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-vaccination day as compared to pre-dose 1 is reported. |
| Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 15, Day 29, Day 43, and Day 56 | Serum was collected pre-challenge at Day 1 (pre-dose 1), Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgG antibody response against Invaplex (a Shigella sonnei antigen complex) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-vaccination day as compared to pre-dose 1 is reported. |
| Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 15, Day 29, Day 43, and Day 56 | Serum was collected pre-challenge at Day 1 (pre-dose 1), Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgA antibody response against LPS (a Shigella sonnei antigen) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-vaccination day as compared to pre-dose 1 is reported. |
| Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 15, Day 29, Day 43, and Day 56 | Serum was collected pre-challenge at Day 1 (pre-dose 1), Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgA antibody response against Invaplex (a Shigella sonnei antigen complex) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-vaccination day as compared to pre-dose 1 is reported. |
| Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Day 15 through Day 56 | Serum was collected post-vaccination and pre-challenge at Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgG and IgA antibody responses against LPS and Invaplex (Shigella sonnei antigens) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The maximum titer per participant between first vaccination (Day 1) and challenge (Day 57) is summarized by study arm via geometric mean and 95% confidence interval. |
| Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Day 15 through Day 56 | Serum was collected post-vaccination and pre-challenge at Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgG and IgA antibody responses against LPS and Invaplex (Shigella sonnei antigens) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The peak fold-rise is calculated per participant at the maximum titer value post-vaccination (and before challenge) compared to pre-vaccination and is summarized by study arm via geometric mean fold-rise and 95% confidence interval. |
| Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 64, Day 71, Day 85, and Day 113 | Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgG antibody response against LPS (a Shigella sonnei antigen) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-challenge day as compared to pre-challenge is reported. |
| Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 64, Day 71, Day 85, and Day 113 | Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgG antibody response against Invaplex (a Shigella sonnei antigen complex) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-challenge day as compared to pre-challenge is reported. |
| Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 64, Day 71, Day 85, and Day 113 | Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgA antibody response against LPS (a Shigella sonnei antigen) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-challenge day as compared to pre-challenge is reported. |
| Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 64, Day 71, Day 85, and Day 113 | Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgA antibody response against Invaplex (a Shigella sonnei antigen complex) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-challenge day as compared to pre-challenge is reported. |
| Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Day 64 through Day 113 | Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgG and IgA antibody responses against LPS and Invaplex (Shigella sonnei antigens) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The maximum titer per participant between challenge (Day 57) and Day 113 is summarized by study arm via geometric mean and 95% confidence interval. |
| Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Day 64 through Day 113 | Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgG and IgA antibody responses against LPS and Invaplex (Shigella sonnei antigens) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The peak fold-rise is calculated per participant at the maximum titer value post-challenge compared to pre-challenge and is summarized by study arm via geometric mean fold-rise and 95% confidence interval. |
| Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Baseline (day of last culture prior to dose 1) through Day 56 | Stool samples collected at baseline and on Days 4, 8, 15, 29, 32, 36, 43, and 56 were cultured for shedding of Shigella sonnei. For this outcome measure, "baseline" is considered the last day at which culture results were available pre-vaccination (may be at screening visit or Day 1). In the event a subject was unable to produce a bulk stool, rectal swabs were collected for culture. |
| Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 57 (post-challenge) through Day 65 | Stool samples collected on Day 57 (post-challenge) through Day 65 were cultured for shedding of Shigella sonnei strain 53G. In the event a subject was unable to produce a bulk stool, rectal swabs were collected for culture. |
| Mean Duration of Shedding Vaccine Strain Post-vaccination Through Day 56 by Culture. | Day 1 (post-vaccination) through Day 56 | Stool samples collected on Day 1 (post-vaccination) and on Days 4, 8, 15, 29, 32, 36, 43, and 56 were cultured for shedding of Shigella sonnei. In the event a subject was unable to produce a bulk stool, rectal swabs were collected for culture. The duration of shedding is evaluated from the day of the initial positive culture result to the day of the last positive qualitative or quantitative culture, regardless of intermittent negative results. |
| Mean Duration of Shedding 53G Post-challenge Through Day 65 by Culture. | Day 57 (post-challenge) through Day 65 | Stool samples collected on Day 57 (post-challenge) through Day 65 were cultured for shedding of Shigella sonnei strain 53G. In the event a subject was unable to produce a bulk stool, rectal swabs were collected for culture. The duration of shedding is evaluated from the day of the initial positive culture result to the day of the last positive qualitative or quantitative culture, regardless of intermittent negative results. |
Countries
United States
Participant flow
Recruitment details
Participants were healthy males and non-pregnant females, 18-49 years inclusive at the time of first vaccination, who met all eligibility criteria. They were recruited from the general population at the participating study sites. Participants were enrolled between 11Oct2022 and 09Jan2024.
Participants by arm
| Arm | Count |
|---|---|
| WRSs2 + WRSs2 (10^6 Cfu) 10\^6 colony forming units (cfu) of WRSs2 administered orally as a 31 mL suspension on Day 1 and Day 29, followed by challenge with 1.5x10\^3 cfu of wild type Shigella sonnei (S. sonnei) 53G administered orally as a 31 mL suspension on Day 57. | 22 |
| WRSs2 + WRSs2 (5x10^5 Cfu) 5x10\^5 colony forming units (cfu) of WRSs2 administered orally as a 31 mL suspension on Day 1 and Day 29, followed by challenge with 1.5x10\^3 cfu of wild type Shigella sonnei (S. sonnei) 53G administered orally as a 31 mL suspension on Day 57. | 26 |
| Placebo + WRSs2 (10^6 Cfu) Placebo administered orally as a 31 mL solution on Day 1, 10\^6 colony forming units (cfu) of WRSs2 administered orally as a 31 mL suspension on Day 29, and challenge with 1.5x10\^3 cfu of wild type Shigella sonnei (S. sonnei) 53G administered orally as a 31 mL suspension on Day 57. | 23 |
| Placebo + Placebo Placebo administered orally as a 31 mL solution on Day 1 and Day 29, followed by challenge with 1.5x10\^3 cfu of wild type Shigella sonnei (S. sonnei) 53G administered orally as a 31 mL suspension on Day 57. | 37 |
| Total | 108 |
Baseline characteristics
| Characteristic | WRSs2 + WRSs2 (10^6 Cfu) | WRSs2 + WRSs2 (5x10^5 Cfu) | Placebo + WRSs2 (10^6 Cfu) | Placebo + Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 32 years STANDARD_DEVIATION 7.7 | 31.8 years STANDARD_DEVIATION 7.5 | 38.3 years STANDARD_DEVIATION 8.3 | 31.2 years STANDARD_DEVIATION 7.8 | 33 years STANDARD_DEVIATION 8.2 |
| Body Mass Index | 32.69 kg/m^2 STANDARD_DEVIATION 8.33 | 28.29 kg/m^2 STANDARD_DEVIATION 5.17 | 29.17 kg/m^2 STANDARD_DEVIATION 5.93 | 29.72 kg/m^2 STANDARD_DEVIATION 6.89 | 29.86 kg/m^2 STANDARD_DEVIATION 6.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 1 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 24 Participants | 22 Participants | 33 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 6 Participants | 9 Participants | 14 Participants | 33 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 2 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 17 Participants | 18 Participants | 12 Participants | 18 Participants | 65 Participants |
| Region of Enrollment United States | 22 participants | 26 participants | 23 participants | 37 participants | 108 participants |
| Sex: Female, Male Female | 13 Participants | 11 Participants | 12 Participants | 22 Participants | 58 Participants |
| Sex: Female, Male Male | 9 Participants | 15 Participants | 11 Participants | 15 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 26 | 0 / 22 | 0 / 38 |
| other Total, other adverse events | 22 / 22 | 26 / 26 | 20 / 22 | 38 / 38 |
| serious Total, serious adverse events | 0 / 22 | 0 / 26 | 0 / 22 | 0 / 38 |
Outcome results
Primary
The Proportion of Participants With Shigellosis Following Challenge With Shigella Sonnei 53G Through Day 63 in the Pooled Group of Participants Receiving Two Doses of 10^6 Cfu or 5x10^5 Cfu of WRSs2 Compared to Participants Receiving Two Doses of Placebo.
Following study vaccination on Days 1 and 29, participants were admitted to an inpatient facility and challenged with Shigella sonnei strain 53G on Day 57. From challenge through Day 63, all stools passed by challenged participants were graded for consistency, all grade 3-5\* stools were visually assessed for gross blood, and all gross blood-containing stools were confirmed via hemoccult test. A blinded endpoint review committee of independent Shigella experts determined whether shigellosis occurred for each participant based on number, weight, consistency, and hemoccult-positive status of stools, along with the presence of additional enteric symptoms. \*Stool consistency was graded according to the following scale: 1 = Normal stool (best outcome); 2 = Soft stool; 3 = Loose stool; 4 = Watery stool; 5 = Rice water (worst outcome).
Time frame: Day 57 through Day 63
Population: The Full Analysis Population includes all randomized participants who were challenged with complete data for the primary efficacy endpoint. Participants will be analyzed according to the study arm to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | The Proportion of Participants With Shigellosis Following Challenge With Shigella Sonnei 53G Through Day 63 in the Pooled Group of Participants Receiving Two Doses of 10^6 Cfu or 5x10^5 Cfu of WRSs2 Compared to Participants Receiving Two Doses of Placebo. | 0.09 proportion of participants |
| Placebo + Placebo | The Proportion of Participants With Shigellosis Following Challenge With Shigella Sonnei 53G Through Day 63 in the Pooled Group of Participants Receiving Two Doses of 10^6 Cfu or 5x10^5 Cfu of WRSs2 Compared to Participants Receiving Two Doses of Placebo. | 0.81 proportion of participants |
Comparison: The null hypothesis is that the absolute vaccine efficacy (VE) of preventing shigellosis is zero. The alternative hypothesis is that the absolute VE is greater than zero.p-value: <0.00195% CI: [0.71, 0.96]Chi-squared
Secondary
Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113
Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgG and IgA antibody responses against LPS and Invaplex (Shigella sonnei antigens) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The maximum titer per participant between challenge (Day 57) and Day 113 is summarized by study arm via geometric mean and 95% confidence interval.
Time frame: Day 64 through Day 113
Population: This analysis includes participants in the Immunogenicity Population who were challenged. The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-LPS IgG | 1233.8 titer |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-Invaplex IgG | 4525.5 titer |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-LPS IgA | 436.2 titer |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-Invaplex IgA | 590.7 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-Invaplex IgG | 4887.8 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-LPS IgA | 400.0 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-Invaplex IgA | 565.7 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-LPS IgG | 1175.8 titer |
| Placebo + WRSs2 (10^6 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-LPS IgA | 275.4 titer |
| Placebo + WRSs2 (10^6 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-Invaplex IgG | 1600.0 titer |
| Placebo + WRSs2 (10^6 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-Invaplex IgA | 323.2 titer |
| Placebo + WRSs2 (10^6 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-LPS IgG | 843.8 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-Invaplex IgA | 1557.9 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-Invaplex IgG | 6400.0 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-LPS IgG | 2145.3 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-challenge Through Day 113 | Anti-LPS IgA | 1044.4 titer |
Secondary
Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56
Serum was collected post-vaccination and pre-challenge at Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgG and IgA antibody responses against LPS and Invaplex (Shigella sonnei antigens) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The maximum titer per participant between first vaccination (Day 1) and challenge (Day 57) is summarized by study arm via geometric mean and 95% confidence interval.
Time frame: Day 15 through Day 56
Population: The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-LPS IgG | 1758.6 titer |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-Invaplex IgG | 5467.2 titer |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-Invaplex IgA | 1814.9 titer |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-LPS IgA | 1062.3 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-Invaplex IgA | 1472.3 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-LPS IgG | 1837.9 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-LPS IgA | 1026.7 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-Invaplex IgG | 5571.5 titer |
| Placebo + WRSs2 (10^6 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-Invaplex IgA | 426.0 titer |
| Placebo + WRSs2 (10^6 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-LPS IgA | 341.7 titer |
| Placebo + WRSs2 (10^6 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-Invaplex IgG | 1873.0 titer |
| Placebo + WRSs2 (10^6 Cfu) | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-LPS IgG | 997.4 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-Invaplex IgG | 1371.6 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-LPS IgG | 423.8 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-LPS IgA | 110.1 titer |
| Placebo + Placebo | Maximum Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer Post-vaccination Through Day 56 | Anti-Invaplex IgA | 110.1 titer |
Secondary
Mean Duration of Shedding 53G Post-challenge Through Day 65 by Culture.
Stool samples collected on Day 57 (post-challenge) through Day 65 were cultured for shedding of Shigella sonnei strain 53G. In the event a subject was unable to produce a bulk stool, rectal swabs were collected for culture. The duration of shedding is evaluated from the day of the initial positive culture result to the day of the last positive qualitative or quantitative culture, regardless of intermittent negative results.
Time frame: Day 57 (post-challenge) through Day 65
Population: This analysis includes participants in the Full Analysis Population with detected Shigella shedding post challenge. The Full Analysis Population includes all randomized participants who were challenged with complete data for the primary efficacy endpoint. Participants were analyzed according to the study arm to which they were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Mean Duration of Shedding 53G Post-challenge Through Day 65 by Culture. | 2.6 days | Standard Deviation 1.3 |
| Placebo + Placebo | Mean Duration of Shedding 53G Post-challenge Through Day 65 by Culture. | 2.6 days | Standard Deviation 1.2 |
| Placebo + WRSs2 (10^6 Cfu) | Mean Duration of Shedding 53G Post-challenge Through Day 65 by Culture. | 2.5 days | Standard Deviation 1.3 |
| Placebo + Placebo | Mean Duration of Shedding 53G Post-challenge Through Day 65 by Culture. | 3.1 days | Standard Deviation 1.3 |
Secondary
Mean Duration of Shedding Vaccine Strain Post-vaccination Through Day 56 by Culture.
Stool samples collected on Day 1 (post-vaccination) and on Days 4, 8, 15, 29, 32, 36, 43, and 56 were cultured for shedding of Shigella sonnei. In the event a subject was unable to produce a bulk stool, rectal swabs were collected for culture. The duration of shedding is evaluated from the day of the initial positive culture result to the day of the last positive qualitative or quantitative culture, regardless of intermittent negative results.
Time frame: Day 1 (post-vaccination) through Day 56
Population: This analysis includes participants in the Shedding Analysis Population with detected Shigella shedding post vaccination and prior to challenge. The Shedding Analysis Population consists of all participants who received any study product. Participants were analyzed according to the study product they actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Mean Duration of Shedding Vaccine Strain Post-vaccination Through Day 56 by Culture. | 21.9 days | Standard Deviation 14.6 |
| Placebo + Placebo | Mean Duration of Shedding Vaccine Strain Post-vaccination Through Day 56 by Culture. | 15.9 days | Standard Deviation 15 |
| Placebo + WRSs2 (10^6 Cfu) | Mean Duration of Shedding Vaccine Strain Post-vaccination Through Day 56 by Culture. | 13.3 days | Standard Deviation 10.3 |
| Placebo + Placebo | Mean Duration of Shedding Vaccine Strain Post-vaccination Through Day 56 by Culture. | 1.0 days | — |
Secondary
Number and Percentage of Participants With SAEs Through Study Day 180 or Until Resolution or Stabilization Even if This Extends Beyond the Study-reporting Period.
An AE or suspected adverse reaction is considered serious if, in the view of either the investigator or sponsor, it results in any of the following outcomes: * Death * A life-threatening AE * Inpatient hospitalization or prolongation of existing hospitalization * A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions * A congenital anomaly/birth defect * Important medical events that may not result in death, be life-threatening, or require hospitalizations may be considered serious when, based upon appropriate medical judgment they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Time frame: Day 1 through Day 180
Population: The Safety Population includes all participants who received at least one dose of study vaccination. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number and Percentage of Participants With SAEs Through Study Day 180 or Until Resolution or Stabilization Even if This Extends Beyond the Study-reporting Period. | 0 Participants |
| Placebo + Placebo | Number and Percentage of Participants With SAEs Through Study Day 180 or Until Resolution or Stabilization Even if This Extends Beyond the Study-reporting Period. | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number and Percentage of Participants With SAEs Through Study Day 180 or Until Resolution or Stabilization Even if This Extends Beyond the Study-reporting Period. | 0 Participants |
| Placebo + Placebo | Number and Percentage of Participants With SAEs Through Study Day 180 or Until Resolution or Stabilization Even if This Extends Beyond the Study-reporting Period. | 0 Participants |
Secondary
Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination.
Systemic solicited adverse events (AEs) were collected pre-vaccination, 90 minutes post-vaccination, and then daily for 7 days after each vaccination using a memory aid and graded on a scale of 0 (none), 1 (mild), 2 (moderate) and 3 (severe). Systemic events include fever, headache, arthralgia, nausea, pain/abdominal cramps, fatigue/malaise, myalgia, anorexia/loss of appetite, chills, vomiting, and diarrhea.
Time frame: Day 1 through Day 8, Day 29 through Day 36
Population: The Safety Population includes all participants who received at least one dose of study vaccination. The number of participants analyzed for solicited systemic AEs after each vaccination reflects the number of participants in the Safety Population who received the corresponding vaccination. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination. | Post first vaccination (Day 1 through Day 8) | 17 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination. | Post second vaccination (Day 29 through Day 36) | 13 Participants |
| Placebo + Placebo | Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination. | Post second vaccination (Day 29 through Day 36) | 17 Participants |
| Placebo + Placebo | Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination. | Post first vaccination (Day 1 through Day 8) | 22 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination. | Post first vaccination (Day 1 through Day 8) | 11 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination. | Post second vaccination (Day 29 through Day 36) | 11 Participants |
| Placebo + Placebo | Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination. | Post first vaccination (Day 1 through Day 8) | 27 Participants |
| Placebo + Placebo | Number and Percentage of Participants With Solicited Systemic Adverse Events (AEs) Through 7 Days After Each Study Vaccination. | Post second vaccination (Day 29 through Day 36) | 22 Participants |
Secondary
Number and Percentage of Participants With Vaccine-related Unsolicited AEs Through 28 Days Post Last Vaccination
ICH E6 defines an AE as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product regardless of its causal relationship to the study treatment. FDA defines an AE as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. The occurrence of an AE may come to the attention of study personnel during study visits and interviews of a study recipient presenting for medical care, or upon review by a study monitor. An AE is considered related if there is a reasonable possibility that the study product caused the AE. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the AE.
Time frame: Day 1 through Day 57
Population: The Safety Population includes all participants who received at least one dose of study vaccination. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number and Percentage of Participants With Vaccine-related Unsolicited AEs Through 28 Days Post Last Vaccination | 2 Participants |
| Placebo + Placebo | Number and Percentage of Participants With Vaccine-related Unsolicited AEs Through 28 Days Post Last Vaccination | 5 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number and Percentage of Participants With Vaccine-related Unsolicited AEs Through 28 Days Post Last Vaccination | 2 Participants |
| Placebo + Placebo | Number and Percentage of Participants With Vaccine-related Unsolicited AEs Through 28 Days Post Last Vaccination | 0 Participants |
Secondary
Number of Participants Shedding 53G in Their Stool by Culture Post-challenge
Stool samples collected on Day 57 (post-challenge) through Day 65 were cultured for shedding of Shigella sonnei strain 53G. In the event a subject was unable to produce a bulk stool, rectal swabs were collected for culture.
Time frame: Day 57 (post-challenge) through Day 65
Population: The Full Analysis Population includes all randomized participants who were challenged with complete data for the primary efficacy endpoint. Participants were analyzed according to the study arm to which they were randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 58 | 0 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 57 | 0 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 65 | 0 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 64 | 0 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 62 | 7 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 61 | 9 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 60 | 6 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 59 | 4 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 63 | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 57 | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 58 | 1 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 62 | 4 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 63 | 1 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 64 | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 65 | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 59 | 3 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 60 | 3 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 61 | 6 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 57 | 3 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 63 | 1 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 58 | 2 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 61 | 5 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 59 | 2 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 62 | 3 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 60 | 4 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 64 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 65 | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 63 | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 65 | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 61 | 13 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 64 | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 58 | 5 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 62 | 13 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 60 | 19 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 57 | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding 53G in Their Stool by Culture Post-challenge | Day 59 | 19 Participants |
Secondary
Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge
Stool samples collected at baseline and on Days 4, 8, 15, 29, 32, 36, 43, and 56 were cultured for shedding of Shigella sonnei. For this outcome measure, baseline is considered the last day at which culture results were available pre-vaccination (may be at screening visit or Day 1). In the event a subject was unable to produce a bulk stool, rectal swabs were collected for culture.
Time frame: Baseline (day of last culture prior to dose 1) through Day 56
Population: The Shedding Analysis Population consists of all participants who received any study product. Participants were analyzed according to the study product they actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Baseline (Pre-Dose 1) | 0 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 15 (Post-Dose 1) | 3 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 43 (Post-Dose 2) | 2 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 56 (Post-Dose 2) | 0 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 8 (Post-Dose 1) | 15 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 32 (Post-Dose 2) | 7 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 29 (Pre-Dose 2) | 4 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 4 (Post-Dose 1) | 15 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 36 (Post-Dose 2) | 3 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 36 (Post-Dose 2) | 4 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 15 (Post-Dose 1) | 10 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 29 (Pre-Dose 2) | 6 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 43 (Post-Dose 2) | 1 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 8 (Post-Dose 1) | 19 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 4 (Post-Dose 1) | 14 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Baseline (Pre-Dose 1) | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 56 (Post-Dose 2) | 2 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 32 (Post-Dose 2) | 5 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 36 (Post-Dose 2) | 9 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Baseline (Pre-Dose 1) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 4 (Post-Dose 1) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 29 (Pre-Dose 2) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 32 (Post-Dose 2) | 9 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 8 (Post-Dose 1) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 15 (Post-Dose 1) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 43 (Post-Dose 2) | 6 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 56 (Post-Dose 2) | 4 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Baseline (Pre-Dose 1) | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 29 (Pre-Dose 2) | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 15 (Post-Dose 1) | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 56 (Post-Dose 2) | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 43 (Post-Dose 2) | 1 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 4 (Post-Dose 1) | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 8 (Post-Dose 1) | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 36 (Post-Dose 2) | 0 Participants |
| Placebo + Placebo | Number of Participants Shedding Vaccine Strain in Their Stool by Culture Prior to Challenge | Day 32 (Post-Dose 2) | 0 Participants |
Secondary
Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A)
Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgA antibody response against Invaplex (a Shigella sonnei antigen complex) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-challenge day as compared to pre-challenge is reported.
Time frame: Day 64, Day 71, Day 85, and Day 113
Population: This analysis includes participants in the Immunogenicity Population who were challenged. The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 64 | 3 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 71 | 5 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 85 | 3 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 113 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 113 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 85 | 3 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 71 | 8 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 64 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 113 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 71 | 1 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 85 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 64 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 113 | 9 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 71 | 22 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 64 | 13 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgA (Immunoglobulin A) | Day 85 | 22 Participants |
Secondary
Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G)
Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgG antibody response against Invaplex (a Shigella sonnei antigen complex) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-challenge day as compared to pre-challenge is reported.
Time frame: Day 64, Day 71, Day 85, and Day 113
Population: This analysis includes participants in the Immunogenicity Population who were challenged. The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 64 | 1 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 71 | 4 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 85 | 1 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 113 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 71 | 1 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 85 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 113 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 64 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 85 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 71 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 113 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 64 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 113 | 14 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 71 | 20 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 64 | 4 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-Invaplex IgG (Immunoglobulin G) | Day 85 | 15 Participants |
Secondary
Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A)
Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgA antibody response against LPS (a Shigella sonnei antigen) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-challenge day as compared to pre-challenge is reported.
Time frame: Day 64, Day 71, Day 85, and Day 113
Population: This analysis includes participants in the Immunogenicity Population who were challenged. The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 113 | 0 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 71 | 7 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 85 | 1 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 64 | 2 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 71 | 7 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 64 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 113 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 85 | 2 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 64 | 1 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 71 | 1 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 113 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 85 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 64 | 13 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 85 | 17 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 71 | 24 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 113 | 7 Participants |
Secondary
Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G)
Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgG antibody response against LPS (a Shigella sonnei antigen) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-challenge day as compared to pre-challenge is reported.
Time frame: Day 64, Day 71, Day 85, and Day 113
Population: This analysis includes participants in the Immunogenicity Population who were challenged. The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 64 | 1 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 71 | 2 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 85 | 1 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 113 | 1 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 71 | 1 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 85 | 1 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 113 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 64 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 85 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 71 | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 113 | 1 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 64 | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 113 | 12 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 71 | 20 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 64 | 3 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 85 | 16 Participants |
Secondary
Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A)
Serum was collected pre-challenge at Day 1 (pre-dose 1), Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgA antibody response against Invaplex (a Shigella sonnei antigen complex) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-vaccination day as compared to pre-dose 1 is reported.
Time frame: Day 15, Day 29, Day 43, and Day 56
Population: The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 15 (Post-Dose 1) | 20 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 43 (Post-Dose 2) | 16 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 29 (Pre-Dose 2) | 14 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 56 (Post-Dose 2) | 9 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 43 (Post-Dose 2) | 15 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 15 (Post-Dose 1) | 24 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 29 (Pre-Dose 2) | 21 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 56 (Post-Dose 2) | 9 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 43 (Post-Dose 2) | 13 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 29 (Pre-Dose 2) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 15 (Post-Dose 1) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 56 (Post-Dose 2) | 13 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 15 (Post-Dose 1) | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 29 (Pre-Dose 2) | 1 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 56 (Post-Dose 2) | 2 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgA (Immunoglobulin A) | Day 43 (Post-Dose 2) | 3 Participants |
Secondary
Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G)
Serum was collected pre-challenge at Day 1 (pre-dose 1), Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgG antibody response against Invaplex (a Shigella sonnei antigen complex) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-vaccination day as compared to pre-dose 1 is reported.
Time frame: Day 15, Day 29, Day 43, and Day 56
Population: The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 29 (Pre-Dose 2) | 16 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 43 (Post-Dose 2) | 14 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 56 (Post-Dose 2) | 11 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 15 (Post-Dose 1) | 16 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 56 (Post-Dose 2) | 9 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 43 (Post-Dose 2) | 10 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 15 (Post-Dose 1) | 13 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 29 (Pre-Dose 2) | 11 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 29 (Pre-Dose 2) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 15 (Post-Dose 1) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 43 (Post-Dose 2) | 9 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 56 (Post-Dose 2) | 9 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 43 (Post-Dose 2) | 1 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 56 (Post-Dose 2) | 1 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 15 (Post-Dose 1) | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-Invaplex IgG (Immunoglobulin G) | Day 29 (Pre-Dose 2) | 0 Participants |
Secondary
Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A)
Serum was collected pre-challenge at Day 1 (pre-dose 1), Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgA antibody response against LPS (a Shigella sonnei antigen) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-vaccination day as compared to pre-dose 1 is reported.
Time frame: Day 15, Day 29, Day 43, and Day 56
Population: The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 15 (Post-Dose 1) | 19 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 43 (Post-Dose 2) | 9 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 29 (Pre-Dose 2) | 12 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 56 (Post-Dose 2) | 6 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 43 (Post-Dose 2) | 12 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 15 (Post-Dose 1) | 24 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 29 (Pre-Dose 2) | 18 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 56 (Post-Dose 2) | 6 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 43 (Post-Dose 2) | 13 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 29 (Pre-Dose 2) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 15 (Post-Dose 1) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 56 (Post-Dose 2) | 10 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 15 (Post-Dose 1) | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 29 (Pre-Dose 2) | 1 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 56 (Post-Dose 2) | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgA (Immunoglobulin A) | Day 43 (Post-Dose 2) | 1 Participants |
Secondary
Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G)
Serum was collected pre-challenge at Day 1 (pre-dose 1), Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgG antibody response against LPS (a Shigella sonnei antigen) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The number of participants with at least a 4-fold rise in antibody titer on each post-vaccination day as compared to pre-dose 1 is reported.
Time frame: Day 15, Day 29, Day 43, and Day 56
Population: The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 15 (Post-Dose 1) | 16 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 29 (Pre-Dose 2) | 13 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 43 (Post-Dose 2) | 9 Participants |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 56 (Post-Dose 2) | 8 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 29 (Pre-Dose 2) | 12 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 43 (Post-Dose 2) | 9 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 56 (Post-Dose 2) | 7 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 15 (Post-Dose 1) | 19 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 43 (Post-Dose 2) | 9 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 29 (Pre-Dose 2) | 0 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 56 (Post-Dose 2) | 7 Participants |
| Placebo + WRSs2 (10^6 Cfu) | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 15 (Post-Dose 1) | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 56 (Post-Dose 2) | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 29 (Pre-Dose 2) | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 15 (Post-Dose 1) | 0 Participants |
| Placebo + Placebo | Number of Participants With >=4-fold Rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) IgG (Immunoglobulin G) | Day 43 (Post-Dose 2) | 0 Participants |
Secondary
Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer
Serum was collected post-challenge at Days 64, 71, 85, and 113 to assess IgG and IgA antibody responses against LPS and Invaplex (Shigella sonnei antigens) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The peak fold-rise is calculated per participant at the maximum titer value post-challenge compared to pre-challenge and is summarized by study arm via geometric mean fold-rise and 95% confidence interval.
Time frame: Day 64 through Day 113
Population: This analysis includes participants in the Immunogenicity Population who were challenged. The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgG | 1.8 fold rise from pre-challenge |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgG | 1.9 fold rise from pre-challenge |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgA | 2.6 fold rise from pre-challenge |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgA | 2.5 fold rise from pre-challenge |
| Placebo + Placebo | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgG | 1.2 fold rise from pre-challenge |
| Placebo + Placebo | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgA | 2.2 fold rise from pre-challenge |
| Placebo + Placebo | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgA | 2.5 fold rise from pre-challenge |
| Placebo + Placebo | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgG | 1.2 fold rise from pre-challenge |
| Placebo + WRSs2 (10^6 Cfu) | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgA | 1.2 fold rise from pre-challenge |
| Placebo + WRSs2 (10^6 Cfu) | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgG | 1.0 fold rise from pre-challenge |
| Placebo + WRSs2 (10^6 Cfu) | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgA | 0.8 fold rise from pre-challenge |
| Placebo + WRSs2 (10^6 Cfu) | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgG | 1.1 fold rise from pre-challenge |
| Placebo + Placebo | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgA | 18.3 fold rise from pre-challenge |
| Placebo + Placebo | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgG | 5.8 fold rise from pre-challenge |
| Placebo + Placebo | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgG | 6.1 fold rise from pre-challenge |
| Placebo + Placebo | Peak Fold-rise From Pre-challenge in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgA | 12.9 fold rise from pre-challenge |
Secondary
Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer
Serum was collected post-vaccination and pre-challenge at Day 15 (post-dose 1), Day 29 (pre-dose 2), Day 43 (post-dose 2), and Day 56 (post-dose 2) to assess IgG and IgA antibody responses against LPS and Invaplex (Shigella sonnei antigens) as measured by Enzyme Linked ImmunoSorbent Assay (ELISA). The peak fold-rise is calculated per participant at the maximum titer value post-vaccination (and before challenge) compared to pre-vaccination and is summarized by study arm via geometric mean fold-rise and 95% confidence interval.
Time frame: Day 15 through Day 56
Population: The Immunogenicity Population consists of all participants who received any study product and for whom immunogenicity endpoint data are available. Participants were analyzed according to the study product actually received, not necessarily the study product to which a participant was randomized.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgG | 5.0 fold rise from pre-vaccination |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgG | 7.8 fold rise from pre-vaccination |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgA | 12.0 fold rise from pre-vaccination |
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgA | 20.6 fold rise from pre-vaccination |
| Placebo + Placebo | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgA | 14.3 fold rise from pre-vaccination |
| Placebo + Placebo | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgG | 4.1 fold rise from pre-vaccination |
| Placebo + Placebo | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgG | 3.3 fold rise from pre-vaccination |
| Placebo + Placebo | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgA | 11.8 fold rise from pre-vaccination |
| Placebo + WRSs2 (10^6 Cfu) | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgG | 3.1 fold rise from pre-vaccination |
| Placebo + WRSs2 (10^6 Cfu) | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgA | 4.3 fold rise from pre-vaccination |
| Placebo + WRSs2 (10^6 Cfu) | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgG | 3.2 fold rise from pre-vaccination |
| Placebo + WRSs2 (10^6 Cfu) | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgA | 6.2 fold rise from pre-vaccination |
| Placebo + Placebo | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgG | 1.2 fold rise from pre-vaccination |
| Placebo + Placebo | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgG | 1.3 fold rise from pre-vaccination |
| Placebo + Placebo | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-Invaplex IgA | 1.4 fold rise from pre-vaccination |
| Placebo + Placebo | Peak Fold-rise From Pre-vaccination in Anti-LPS (Lipopolysaccharide) and Anti-Invaplex Serum IgG (Immunoglobulin G) and IgA (Immunoglobulin A) Titer | Anti-LPS IgA | 1.2 fold rise from pre-vaccination |
Secondary
The Proportion of Participants With Shigellosis Following Challenge With S. Sonnei 53G Through Day 63 in Participants Receiving 1 Dose of 10^6 Cfu, 2 Doses of 10^6 Cfu, or 2 Doses of 5x10^5 Cfu of WRSs2 Compared to Those Receiving Two Doses of Placebo.
Following study vaccination on Days 1 and 29, participants were admitted to an inpatient facility and challenged with Shigella sonnei strain 53G on Day 57. From challenge through Day 63, all stools passed by challenged participants were graded for consistency, all grade 3-5\* stools were visually assessed for gross blood, and all gross blood-containing stools were confirmed via hemoccult test. A blinded endpoint review committee of independent Shigella experts determined whether shigellosis occurred for each participant based on number, weight, consistency, and hemoccult-positive status of stools, along with the presence of additional enteric symptoms. \*Stool consistency was graded according to the following scale: 1 = Normal stool (best outcome); 2 = Soft stool; 3 = Loose stool; 4 = Watery stool; 5 = Rice water (worst outcome).
Time frame: Day 57 through Day 65
Population: The Full Analysis Population includes all randomized participants who were challenged with complete data for the primary efficacy endpoint. Participants were analyzed according to the study arm to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WRSs2 + WRSs2 (10^6 Cfu or 5x10^5 Cfu) | The Proportion of Participants With Shigellosis Following Challenge With S. Sonnei 53G Through Day 63 in Participants Receiving 1 Dose of 10^6 Cfu, 2 Doses of 10^6 Cfu, or 2 Doses of 5x10^5 Cfu of WRSs2 Compared to Those Receiving Two Doses of Placebo. | 0.19 proportion of participants |
| Placebo + Placebo | The Proportion of Participants With Shigellosis Following Challenge With S. Sonnei 53G Through Day 63 in Participants Receiving 1 Dose of 10^6 Cfu, 2 Doses of 10^6 Cfu, or 2 Doses of 5x10^5 Cfu of WRSs2 Compared to Those Receiving Two Doses of Placebo. | 0 proportion of participants |
| Placebo + WRSs2 (10^6 Cfu) | The Proportion of Participants With Shigellosis Following Challenge With S. Sonnei 53G Through Day 63 in Participants Receiving 1 Dose of 10^6 Cfu, 2 Doses of 10^6 Cfu, or 2 Doses of 5x10^5 Cfu of WRSs2 Compared to Those Receiving Two Doses of Placebo. | 0 proportion of participants |
| Placebo + Placebo | The Proportion of Participants With Shigellosis Following Challenge With S. Sonnei 53G Through Day 63 in Participants Receiving 1 Dose of 10^6 Cfu, 2 Doses of 10^6 Cfu, or 2 Doses of 5x10^5 Cfu of WRSs2 Compared to Those Receiving Two Doses of Placebo. | 0.81 proportion of participants |
95% CI: [0.44, 0.92]
95% CI: [0.78, 1]
95% CI: [0.71, 1]