About this trial
Cellular and humoral immune responses before and after seasonal influenza vaccination will be assessed. Each year, up to 100 participants will be enrolled. To study age-specific differences in immune responses, participants with various years of birth will be enrolled. The investigators hypothesize that humans with different birth years will mount antibody and cellular responses of different specificities following seasonal influenza vaccination.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for all study visits
Aged 18 years and older
In good health based on self-reported medical conditions via an online survey
Disqualifiers
Known allergic reactions to components of the study vaccine
Known latex allergy
History of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines
History of GBS within 6 weeks of receipt of a previous influenza vaccine
Trial design
Single group
Treatments tested in this trial
Seasonal influenza vaccine
Biological/VaccineThe seasonal influenza vaccine is administered intramuscularly at a dose of 15 ug of HA per component, as approved by the FDA.
Treatment groups
Trial outcomes
Primary outcomes
Effect of year of birth on neutralizing antibody titers elicited by influenza vaccination
Because year of birth can be used to predict the influenza viruses circulating during the first years of life, assessing antibody responses in individuals of different birth years is one way of determining how prior exposure affects immune responses to seasonal influenza vaccination and infection. The investigators will assess how antibody responses to seasonal influenza vaccination differ in individuals across multiple age groups. Baseline serum neutralizing antibodies to post-vaccination serum neutralizing antibodies against the influenza A (H1N1 and H3N2) and influenza B viral strains that are included in the quadrivalent influenza vaccine will be compared. The investigators will compare neutralizing antibody titers between groups of individuals with different birth years. Neutralizing antibody titers against the vaccine strains will be quantified by focus reduction neutralization test (FRNT) and data will be expressed as FRNT titer.
Secondary outcomes
Changes in serum HAI antibodies in individuals of different birth years following influenza vaccination
Baseline serum antibodies will be compared to those collected after vaccination to access changes in serum hemagglutination inhibition (HAI) antibodies that block virus binding to cells. Titer will be defined as the highest dilution resulting in complete inhibition of hemagglutination in the assay. The changes measured in HAI titer between pre and post vaccination will be compared among individuals of different birth years.
Differences in levels of HA stalk-binding antibodies in individuals of different birth years following influenza vaccination
Baseline serum antibodies will be compared to post-vaccination serum antibodies to assess differences in levels (increase or decrease) of reactive antibodies to the HA stalk of influenza viruses. Serum antibody titers will be measured by ELISA using "headless" HA to quantify serum antibodies targeting the HA stalk. Antibody titers measured in pre and post vaccination sera will be compared among individuals of different birth years. Data will be expressed as ELISA relative units.
Differences in levels of NA-binding antibodies in individuals of different birth years following influenza vaccination
Baseline serum antibodies will be compared to post-vaccination serum antibodies to assess changes in levels (increase or decrease) of antibodies that inhibit NA activity (NA-binding antibodies) of different influenza viruses. NA activity will be measured via an enzyme-linked lectin assay (ELLA) and the amount of serum antibody present that inhibits NA activity of different influenza strains will be quantified. These titers measured in pre and post vaccination sera will be compared among individuals of different birth years. Data will be expressed as ELLA titer.
Assessment of the frequency of circulating T follicular helper cell response to influenza vaccination in individuals of different birth years
Circulating T follicular helper cells (cTfh) with be assessed among peripheral blood mononuclear cells (PBMCs) collected at baseline and after vaccination. Frequencies, defined by percent increase or decrease, will be measured by flow cytometry-based assays. Measurement of the frequencies of cTfh in response to influenza vaccination will be compared among individuals of different birth years to determine the effect of year of birth on cTfh responses following influenza vaccination.
Sponsors and contacts
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University of Pennsylvania
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator
Stanford University
Collaborator
The Scripps Research Institute
Collaborator