Healthy
Conditions
Keywords
immune response
Brief summary
In order to produce better more effective vaccines, it is important to understand the particulars of why individuals have an effective or ineffective immune response to vaccination. We are going to examine specific aspects of the antibody (IgG Fc glycan) made by healthy volunteers who receive different vaccines or who have a viral infection to understand the nature of an effective (or less effective) vaccine response. The results of this research could be used to develop adjuvants to increase/ improve vaccine response.
Detailed description
Antibodies are principle mediators of immunity against infections and they can also give rise to autoimmune and inflammatory diseases. Two functional domains make up an IgG antibody - the Fab domain binds to a specific target, while the Fc domain can interact with receptor molecules to activate a pro- or anti- inflammatory state. The Fc domain of IgGs contains a glycan that is variable in composition and its specific sugar components are an important determinant of the biologic activity of IgGs in both protective and pathologic immune responses. New disease treatments could be developed through purposeful manipulation of IgG Fc glycans, but there is currently little known about how Fc glycan composition is regulated. We plan to study this by evaluating whether vaccination can cause changes in Fc glycan composition and, if so, whether signaling from helper T cells, age of the patient, and/or route of vaccine administration are determinants of specific modifications that are triggered by vaccination. Next, we will study effects that specific components within the Fc glycan have on immunity against the common human pathogens Streptococcus pneumoniae and influenza viruses using in vitro and in vivo models of infection. We will also study whether healthy adults who have been previously infected with dengue, zika or chikungunya virus generate distinct Fc glycoforms after vaccination compared with healthy adults who have not been previously infected with any of these viruses.
Interventions
BIOLOGICALIM Pneumococcal, meningococcal, or flu vaccine
Volunteers given one of the 3 vaccines
Sponsors
Rockefeller University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or Female 18-80 years of age * Healthy volunteers without significant medical problems * Able to give informed consent to participate * Willing to receive a single dose of an FDA-approved vaccine (either the influenza virus, pneumococcal or meningococcal vaccine) * Documented previous infection with dengue, zika or chikungunya virus or no history of dengue, zika or chikungunya infection.
Exclusion criteria
* Prior allergic reaction to commercial vaccination * For Flumist participants: Close contact with person with severely compromised immune system requiring isolation * For Flumist participants: Current illness that limits delivery to nasal airway (mild illness, such as diarrhea or mild respiratory infection with or without fever, and local infections do not apply) * History of seizure disorder for Flumist group participants only. * Participation in another clinical study of an investigational product currently or within the past 90 days, or expected participation during this study. * Any clinically significant acute or chronic medical condition requiring care of a physician (e.g., diabetes, coronary artery disease, rheumatologic illness, malignancy, substance abuse) that, in the opinion of the investigator, would preclude participation. * In the opinion of the investigator, the volunteer is unlikely to comply with the study protocol. * Currently taking systemic steroids or other immunomodulatory medications including anticancer medications and antiviral medications. * Egg allergy * Received the influenza vaccine less than 1 month ago and/or received the pneumococcal and meningococcal vaccine less than 4 years ago * Confirmed HIV infection, positive for hepatitis B surface antigen or positive for hepatitis C antibodies. * Is pregnant or lactating * History of Guillain-Barre syndrome * Poor venous access * Unable to continue participation for 12 weeks * Any clinically significant abnormality on medical history or physical examination including history of immunodeficiency or autoimmune disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percent (of 100%) of IgG With Galactosylation, Fucosylation and/or Sialylation | One Day | The percent of Fc glycans that are galactosylation, fucosylation and/or sialylation of pre- vs. post- vaccination Fcs determined by lectin blot (Erythrina cristagalli, Aleuria Aurantia Lectin and Sambucus nigra lectins specific for galactose, fucose and 2,6-sialic acid, respectively) or by mass spectrometric analysis. 100% of IgG were found to have these modifications. |
Countries
United States
Participant flow
Recruitment details
3 study arms were intended, as described here.
Pre-assignment details
129 participants were consented; 38 were not assigned to an arm because they screened out
Participants by arm
| Arm | Count |
|---|---|
| Biologic/Vaccine, Age 18-64 Cohort Vaccination. IM Pneumococcal, meningococcal, or flu vaccine
IM Pneumococcal, meningococcal, or flu vaccine: Volunteers given one of the 3 vaccines | 53 |
| Biologic/Vaccine, Age 65-80 Cohort Vaccination. IM Pneumococcal, meningococcal, or flu vaccine
IM Pneumococcal, meningococcal, or flu vaccine: Volunteers given one of the 3 vaccines | 22 |
| Vaccine, Healthy Adults Vaccination. IM Pneumococcal, meningococcal, or flu vaccine
IM Pneumococcal, meningococcal, or flu vaccine: Volunteers given one of the 3 vaccines | 16 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Biologic/Vaccine, Age 18-64 Cohort | Biologic/Vaccine, Age 65-80 Cohort | Vaccine, Healthy Adults | Total |
|---|---|---|---|---|
| Age, Customized >18 and < 65 years | 53 Participants | 0 Participants | 15 Participants | 68 Participants |
| Age, Customized >= 65 and <= 80 years | 0 Participants | 22 Participants | 1 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 1 Participants | 3 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 18 Participants | 12 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 4 Participants | 0 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 2 Participants | 3 Participants | 14 Participants |
| Race (NIH/OMB) White | 22 Participants | 15 Participants | 10 Participants | 47 Participants |
| Region of Enrollment United States | 53 participants | 22 participants | 16 participants | 91 participants |
| Sex: Female, Male Female | 25 Participants | 17 Participants | 10 Participants | 52 Participants |
| Sex: Female, Male Male | 28 Participants | 5 Participants | 6 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 22 | 0 / 16 |
| other Total, other adverse events | 4 / 53 | 2 / 22 | 3 / 16 |
| serious Total, serious adverse events | 0 / 53 | 0 / 22 | 0 / 16 |
Outcome results
Primary
The Percent (of 100%) of IgG With Galactosylation, Fucosylation and/or Sialylation
The percent of Fc glycans that are galactosylation, fucosylation and/or sialylation of pre- vs. post- vaccination Fcs determined by lectin blot (Erythrina cristagalli, Aleuria Aurantia Lectin and Sambucus nigra lectins specific for galactose, fucose and 2,6-sialic acid, respectively) or by mass spectrometric analysis. 100% of IgG were found to have these modifications.
Time frame: One Day
Population: The primary assessment in the study was intended to compare data for each Arm as shown with no comparisons by vaccine. All groups within Arm 1 were not fully enrolled, therefore it was adequately powered to perform analyses (data were not collected).~Arm 2 was not fully enrolled and underpowered (data were not collected). Samples from Arm 3 were destroyed during the COVID-19 pandemic due to a stalled shipment which caused the samples to thaw for several days (data were not collected).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Biologic/Vaccine, Age 18-64 Cohort | The Percent (of 100%) of IgG With Galactosylation, Fucosylation and/or Sialylation | 100 % of glycosylated IgG |