Influenza
Conditions
Keywords
influenza, vaccine, pandemic
Brief summary
To evaluate the safety profile of two intranasal doses of LAIV A/17/turkey/Turkey/05/133 (H5N2) in healthy adults.
Interventions
BIOLOGICALLAIV H5N2
2 doses provided intranasally
OTHERPlacebo
2 doses of placebo provided intranasally
Sponsors
Microgen
Institute of Experimental Medicine, Russia
PATH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Legal male or female adult 18 through 49 years of age at the enrollment visit. * Literate and willing to provide written informed consent. * Free of obvious health problems, as established by the medical history and screening evaluations, including physical examination. * Capable and willing to complete diary cards and willing to return for all follow-up visits * Willing to comply with the rules of the isolation unit (including willing and able to take oseltamivir influenza antiviral medication, should that be recommended by a study physician). * For females, willing to take reliable birth control measures throughout the entire period of participation in the study.
Exclusion criteria
* Participation in another clinical trial involving any therapy within the previous three months or planned enrollment in such a trial during the period of this study. * Receipt of any non-study vaccine within four weeks prior to enrollment or refusal to postpone receipt of such vaccines until four weeks after study completion. * Practice of nasal irrigation on a regular basis within the past six months or has engaged in nasal irrigation within two weeks prior to enrollment. * Recent history of frequent nose bleeds (\>5 within the past year). * Clinically relevant abnormal paranasal anatomy. * Recent history (within the past month) of rhino or sinus surgery, or surgery for any traumatic injury of the nose. * Current or recent (within two weeks of enrollment) acute respiratory illness with or without fever. * Other acute illness at the time of study enrollment. * Receipt of immune globulin or other blood products within three months prior to study enrollment or planned receipt of such products during the period of subject participation in the study. * Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study enrollment. (For corticosteroids, this means prednisone or equivalent, 0.5 mg per kg per day; topical steroids are allowed, exclusive of nasal.) * Participation in any previous trial of any H5 or H7 containing influenza vaccine. * History of asthma. * Hypersensitivity after previous administration of any influenza vaccine. * History of wheezing after past receipt of any live influenza vaccine. * Other adverse event (AE) following immunization, at least possibly related to previous receipt of any influenza vaccine. * Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein. * Seasonal (autumnal) hypersensitivity to the natural environment. * Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, metabolic, neurologic, psychiatric or renal functional abnormality, as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives. Subjects with physical examination findings or clinical laboratory screening results which would be graded 2 or higher on the AE severity grading scale (see Attachments) will be excluded from entry into the study and will be excluded from receipt of dose two of study vaccine or placebo. * History of leukemia or any other blood or solid organ cancer. * History of thrombocytopenic purpura or known bleeding disorder. * History of seizures. * Known or suspected immunosuppressive or immunodeficient condition of any kind, including HIV infection. * Known chronic hepatitis B (HBV) or hepatitis C (HCV) infection. * Known tuberculosis infection or evidence of previous tuberculosis exposure. * History of chronic alcohol abuse and/or illegal drug use. * Claustrophobia or sociophobia. * Pregnancy or lactation. (A negative pregnancy test will be required before administration of study vaccine or placebo for all women of childbearing potential.) * Any condition that, in the opinion of the investigator, would increase the health risk to the subject if he/she participates in the study or would interfere with the evaluation of the study objectives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events by Severity | 6 days | Occurrence of participants with adverse events associated with intranasal administration, by worst grade of severity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) | 28 days (Dose 1) and 56 days (Dose 2) | IgA = immunoglobulin class A antibodies Determined using ELISA using whole purified H5N2 |
| Number/Percentage of Subjects With Seroconversion for Secretory IgA | 28 days (Dose 1) and 56 days (Dose 2) | IgA antibodies from the nasal mucosa detected in nasal wick specimens. Determined using ELISA using whole purified H5N2 |
| Number/Percentage of Subjects With Seroconversion for IgA in Saliva | 28 days (Dose 1) and 56 days (Dose 2) | IgA = Immunoglobulin Class A antibodies. Determined using ELISA using whole purified H5N2. |
| Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | 6 days post-vaccination | Nasal swabs were collected and used for Reverse transcription polymerase chain reaction (rRTPCR) assays to detect shedding of influenza virus for days 1-6 of the study. |
| Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | 6 days post-vaccination | Nasal swabs were collected and used for Reverse transcription polymerase chain reaction (rRTPCR) assays to detect shedding of influenza virus for days 29-34 of the study (6 days after the second vaccination). |
| Geometric Mean Titers for Serum HAI Antibodies | 0 days, 28 days (Dose 1) and 56 days (Dose 2) | Geometric mean titers for serum hemagglutination inhibition antibodies |
| Geometric Mean Titers (GMT) for Serum Neutralizing Antibodies | 0 days, 28 days (Dose 1) and 56 days (Dose 2) | Geometric mean titers for serum neutralizing antibodies measured by microneutralization assay |
| Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) | 28 days (Dose 1) and 56 days (Dose 2) | Defined as a four-fold or greater antibody rise in titer from pre-vaccination level. HAI = hemagglutination-inhibition, conducted using World Health Organization (WHO)-recommended protocols. |
| Number/Percentage of Subjects With Serum Neutralizing Antibodies | 28 days (Dose 1) and 56 days (Dose 2) | Defined as a four-fold or greater antibody rise in titer from pre-vaccination level. Measured by microneutralization assay in Madin-Darby canine kidney cells (MDCK). |
| Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) | 28 days (Dose 1) and 56 days (Dose 2) | Determined using ELISA using whole purified H5N2. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | 28 days (Dose 1) and 56 days (Dose 2) | Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old ECE followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3SD over the mean placebo values was regarded as a positive T cell response. |
| Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | 28 days (Dose 1) and 56 days (Dose 2) | Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old ECE followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3SD over the mean placebo values was regarded as a positive T cell response. |
| Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | 28 days (Dose 1) and 56 days (Dose 2) | Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old ECE followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3SD over the mean placebo values was regarded as a positive T cell response. |
| Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | 28 days (Dose 1) and 56 days (Dose 2) | Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old ECE followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3SD over the mean placebo values was regarded as a positive T cell response. |
| Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | 28 days (Dose 1) and 56 days (Dose 2) | Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old embryonated chicken eggs (ECE) followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3 standard deviations over the mean placebo values was regarded as a positive T cell response. |
| Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | 28 days (Dose 1) and 56 days (Dose 2) | Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old ECE followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3 standard deviations over the mean placebo values was regarded as a positive T cell response. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LAIV H5N2 Two doses of live monovalent influenza vaccine A/17/turkey/Turkey/05/133 ( live monovalent (LAIV H5N2) given intranasally | 30 |
| Placebo two doses of placebo solution intranasal | 10 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Dose 2 | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Total | LAIV H5N2 | Placebo |
|---|---|---|---|
| Age, Continuous | 28.1 years STANDARD_DEVIATION 10.4 | 27.7 years STANDARD_DEVIATION 10.4 | 29.2 years STANDARD_DEVIATION 10.8 |
| Region of Enrollment Russia | 40 participants | 30 participants | 10 participants |
| Sex: Female, Male Female | 13 Participants | 9 Participants | 4 Participants |
| Sex: Female, Male Male | 27 Participants | 21 Participants | 6 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 / 30 | 0 / 10 | 0 / 29 | 0 / 10 |
| other Total, other adverse events | 21 / 30 | 8 / 30 | 25 / 30 | 8 / 10 |
| serious Total, serious adverse events | 0 / 30 | 0 / 10 | 0 / 29 | 0 / 10 |
Outcome results
Primary
Adverse Events by Severity
Occurrence of participants with adverse events associated with intranasal administration, by worst grade of severity
Time frame: 6 days
Population: All participants that received either a vaccine or placebo, by dose
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Adverse Events by Severity | None | 9 Participants |
| Dose 1: Vaccine | Adverse Events by Severity | Worst grade: mild | 20 Participants |
| Dose 1: Vaccine | Adverse Events by Severity | Worst grade: moderate | 1 Participants |
| Dose 1: Vaccine | Adverse Events by Severity | Worst grade: severe | 0 Participants |
| Dose 1: Placebo | Adverse Events by Severity | None | 2 Participants |
| Dose 1: Placebo | Adverse Events by Severity | Worst grade: moderate | 0 Participants |
| Dose 1: Placebo | Adverse Events by Severity | Worst grade: severe | 0 Participants |
| Dose 1: Placebo | Adverse Events by Severity | Worst grade: mild | 8 Participants |
| Dose 2: Vaccine | Adverse Events by Severity | Worst grade: mild | 25 Participants |
| Dose 2: Vaccine | Adverse Events by Severity | Worst grade: severe | 0 Participants |
| Dose 2: Vaccine | Adverse Events by Severity | Worst grade: moderate | 0 Participants |
| Dose 2: Vaccine | Adverse Events by Severity | None | 4 Participants |
| Dose 2: Placebo | Adverse Events by Severity | Worst grade: severe | 0 Participants |
| Dose 2: Placebo | Adverse Events by Severity | Worst grade: mild | 8 Participants |
| Dose 2: Placebo | Adverse Events by Severity | None | 2 Participants |
| Dose 2: Placebo | Adverse Events by Severity | Worst grade: moderate | 0 Participants |
Secondary
Geometric Mean Titers for Serum HAI Antibodies
Geometric mean titers for serum hemagglutination inhibition antibodies
Time frame: 0 days, 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving both doses of study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Dose 1: Vaccine | Geometric Mean Titers for Serum HAI Antibodies | Day 0 | 2.5 titer |
| Dose 1: Vaccine | Geometric Mean Titers for Serum HAI Antibodies | After dose 1 | 3.5 titer |
| Dose 1: Vaccine | Geometric Mean Titers for Serum HAI Antibodies | After dose 2 | 4.7 titer |
| Dose 1: Placebo | Geometric Mean Titers for Serum HAI Antibodies | Day 0 | 2.7 titer |
| Dose 1: Placebo | Geometric Mean Titers for Serum HAI Antibodies | After dose 1 | 2.7 titer |
| Dose 1: Placebo | Geometric Mean Titers for Serum HAI Antibodies | After dose 2 | 2.9 titer |
Secondary
Geometric Mean Titers (GMT) for Serum Neutralizing Antibodies
Geometric mean titers for serum neutralizing antibodies measured by microneutralization assay
Time frame: 0 days, 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving both doses of study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Dose 1: Vaccine | Geometric Mean Titers (GMT) for Serum Neutralizing Antibodies | Day 0 | 5.2 titer |
| Dose 1: Vaccine | Geometric Mean Titers (GMT) for Serum Neutralizing Antibodies | After dose 1 | 6.7 titer |
| Dose 1: Vaccine | Geometric Mean Titers (GMT) for Serum Neutralizing Antibodies | After dose 2 | 11.8 titer |
| Dose 1: Placebo | Geometric Mean Titers (GMT) for Serum Neutralizing Antibodies | Day 0 | 5.4 titer |
| Dose 1: Placebo | Geometric Mean Titers (GMT) for Serum Neutralizing Antibodies | After dose 1 | 5.4 titer |
| Dose 1: Placebo | Geometric Mean Titers (GMT) for Serum Neutralizing Antibodies | After dose 2 | 5.7 titer |
Secondary
Number/Percentage of Subjects With Seroconversion for IgA in Saliva
IgA = Immunoglobulin Class A antibodies. Determined using ELISA using whole purified H5N2.
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects With Seroconversion for IgA in Saliva | No seroconversion | 27 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects With Seroconversion for IgA in Saliva | Seroconversion | 3 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Seroconversion for IgA in Saliva | No seroconversion | 10 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Seroconversion for IgA in Saliva | Seroconversion | 0 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Seroconversion for IgA in Saliva | Seroconversion | 10 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Seroconversion for IgA in Saliva | No seroconversion | 19 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Seroconversion for IgA in Saliva | Seroconversion | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Seroconversion for IgA in Saliva | No seroconversion | 10 Participants |
Secondary
Number/Percentage of Subjects With Seroconversion for Secretory IgA
IgA antibodies from the nasal mucosa detected in nasal wick specimens. Determined using ELISA using whole purified H5N2
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects With Seroconversion for Secretory IgA | Seroconversion | 2 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects With Seroconversion for Secretory IgA | No seroconversion | 28 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Seroconversion for Secretory IgA | No seroconversion | 10 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Seroconversion for Secretory IgA | Seroconversion | 0 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Seroconversion for Secretory IgA | Seroconversion | 6 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Seroconversion for Secretory IgA | No seroconversion | 23 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Seroconversion for Secretory IgA | Seroconversion | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Seroconversion for Secretory IgA | No seroconversion | 10 Participants |
Secondary
Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI)
Defined as a four-fold or greater antibody rise in titer from pre-vaccination level. HAI = hemagglutination-inhibition, conducted using World Health Organization (WHO)-recommended protocols.
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) | Seroconversion | 4 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) | No seroconversion | 26 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) | No seroconversion | 10 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) | Seroconversion | 0 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) | Seroconversion | 11 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) | No seroconversion | 18 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) | Seroconversion | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) | No seroconversion | 10 Participants |
Secondary
Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA)
IgA = immunoglobulin class A antibodies Determined using ELISA using whole purified H5N2
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) | Seroconversion | 0 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) | No seroconversion | 30 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) | No seroconversion | 10 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) | Seroconversion | 0 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) | Seroconversion | 2 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) | No seroconversion | 27 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) | Seroconversion | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) | No seroconversion | 10 Participants |
Secondary
Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG)
Determined using ELISA using whole purified H5N2.
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) | Seroconversion | 0 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) | No seroconversion | 30 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) | No seroconversion | 10 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) | Seroconversion | 0 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) | Seroconversion | 1 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) | No seroconversion | 28 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) | Seroconversion | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) | No seroconversion | 10 Participants |
Secondary
Number/Percentage of Subjects With Serum Neutralizing Antibodies
Defined as a four-fold or greater antibody rise in titer from pre-vaccination level. Measured by microneutralization assay in Madin-Darby canine kidney cells (MDCK).
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects With Serum Neutralizing Antibodies | No seroconversion | 27 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects With Serum Neutralizing Antibodies | Seroconversion | 3 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Serum Neutralizing Antibodies | No seroconversion | 10 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects With Serum Neutralizing Antibodies | Seroconversion | 0 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Serum Neutralizing Antibodies | Seroconversion | 14 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects With Serum Neutralizing Antibodies | No seroconversion | 15 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Serum Neutralizing Antibodies | No seroconversion | 10 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects With Serum Neutralizing Antibodies | Seroconversion | 0 Participants |
Secondary
Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose
Nasal swabs were collected and used for Reverse transcription polymerase chain reaction (rRTPCR) assays to detect shedding of influenza virus for days 1-6 of the study.
Time frame: 6 days post-vaccination
Population: Participants receiving first dose of study vaccine and with post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | Shedding | 28 Participants |
| Dose 1: Vaccine | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | No shedding | 2 Participants |
| Dose 1: Placebo | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | No shedding | 25 Participants |
| Dose 1: Placebo | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | Shedding | 5 Participants |
| Dose 2: Vaccine | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | Shedding | 0 Participants |
| Dose 2: Vaccine | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | No shedding | 30 Participants |
| Dose 2: Placebo | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | Shedding | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | No shedding | 30 Participants |
| Day 5 | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | Shedding | 0 Participants |
| Day 5 | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | No shedding | 30 Participants |
| Day 6 | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | Shedding | 0 Participants |
| Day 6 | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | No shedding | 30 Participants |
Secondary
Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose
Nasal swabs were collected and used for Reverse transcription polymerase chain reaction (rRTPCR) assays to detect shedding of influenza virus for days 29-34 of the study (6 days after the second vaccination).
Time frame: 6 days post-vaccination
Population: Participants receiving second dose of study vaccine and with post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | No shedding | 8 Participants |
| Dose 1: Vaccine | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | Shedding | 21 Participants |
| Dose 1: Placebo | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | No shedding | 25 Participants |
| Dose 1: Placebo | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | Shedding | 4 Participants |
| Dose 2: Vaccine | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | No shedding | 29 Participants |
| Dose 2: Vaccine | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | Shedding | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | Shedding | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | No shedding | 29 Participants |
| Day 5 | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | Shedding | 0 Participants |
| Day 5 | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | No shedding | 29 Participants |
| Day 6 | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | Shedding | 0 Participants |
| Day 6 | Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | No shedding | 29 Participants |
Other Pre-specified
Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses
Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old ECE followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3SD over the mean placebo values was regarded as a positive T cell response.
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving both doses of study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | Positive response | 5 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | No response | 24 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | Positive response | 0 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | No response | 10 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | Positive response | 6 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | No response | 23 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | Positive response | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | No response | 10 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | Positive response | 8 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | No response | 21 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | Positive response | 0 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses | No response | 10 Participants |
Other Pre-specified
Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses
Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old ECE followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3SD over the mean placebo values was regarded as a positive T cell response.
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving both doses of study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | No response | 24 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | Positive response | 5 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | Positive response | 0 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | No response | 10 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | Positive response | 6 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | No response | 23 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | Positive response | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | No response | 10 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | Positive response | 11 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | No response | 18 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | Positive response | 0 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses | No response | 10 Participants |
Other Pre-specified
Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses
Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old ECE followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3 standard deviations over the mean placebo values was regarded as a positive T cell response.
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | No response | 26 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | Positive response | 3 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | Positive response | 0 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | No response | 10 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | Positive response | 5 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | No response | 25 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | Positive response | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | No response | 10 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | Positive response | 6 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | No response | 23 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | No response | 10 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses | Positive response | 0 Participants |
Other Pre-specified
Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses
Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old ECE followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3SD over the mean placebo values was regarded as a positive T cell response.
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving both doses of study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | Positive response | 2 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | No response | 27 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | Positive response | 1 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | No response | 9 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | Positive response | 6 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | No response | 23 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | Positive response | 3 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | No response | 7 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | Positive response | 3 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | No response | 26 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | Positive response | 0 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses | No response | 10 Participants |
Other Pre-specified
Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses
Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old ECE followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3SD over the mean placebo values was regarded as a positive T cell response.
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving both doses of study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | Positive response | 6 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | No response | 23 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | Positive response | 0 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | No response | 10 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | Positive response | 3 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | No response | 26 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | Positive response | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | No response | 10 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | Positive response | 8 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | No response | 21 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | Positive response | 0 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses | No response | 10 Participants |
Other Pre-specified
Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses
Nasal swabs from days 1, 2, 3, 5, and 7 after the first vaccination and on days 1 and 3, corresponding to days 29 and 31,respectively, after the second dose were tested for viral shedding by inoculation in 10- to 11-day-old embryonated chicken eggs (ECE) followed by incubation at 32◦C for 72 h. Influenza virus was detected by standard hemagglutination test with 1% chicken red blood cells. An increase in the number of antigenic-specific T cells greater than 3 standard deviations over the mean placebo values was regarded as a positive T cell response.
Time frame: 28 days (Dose 1) and 56 days (Dose 2)
Population: Participants receiving study vaccine or placebo and with pre- and post-vaccination immunologic parameters measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | Positive response | 1 Participants |
| Dose 1: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | No response | 28 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | No response | 10 Participants |
| Dose 1: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | Positive response | 0 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | No response | 27 Participants |
| Dose 2: Vaccine | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | Positive response | 2 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | Positive response | 0 Participants |
| Dose 2: Placebo | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | No response | 10 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | No response | 26 Participants |
| Day 5 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | Positive response | 3 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | No response | 10 Participants |
| Day 6 | Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses | Positive response | 0 Participants |