Back to resultsCharacterization of Humoral and Cellular Immune Responses Elicited by Influenza Vaccination in Healthy Adults
Primary Purpose
Influenza, Human
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Seasonal influenza vaccine
Sponsored by
About this trial
This is an interventional basic science trial for Influenza, Human
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- Immunosuppression as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months
- Treatment with immunoglobulin or another blood product within the 3 months prior to enrollment in this study
- Active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematological malignancy ("active" is defined as having received treatment within the past 5 years)
- Long-term (greater than 2 weeks) usage of oral or parenteral steroids, or high-dose inhaled steroids
- Administration of an influenza vaccine within 2 months prior to enrollment
- Known acute or chronic medical condition that, in the opinion of the investigator or appropriate sub-investigator, would render vaccination unsafe or would interfere with the evaluation of responses
- Participation in a study that involves an experimental agent or having received an experimental agent (other than a COVID-19 vaccine) within 1 month prior to enrollment or expecting to receive another experimental agent during the study period
- Intends to donate blood during the study period
- Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol
- Known human immunodeficiency virus, hepatitis B, or hepatitis C infection
- Any condition that the principal investigator believes may interfere with successful completion of the study
Sites / Locations
- University of PennsylvaniaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Influenza vaccination
Arm Description
Adults will receive a seasonal, inactivated, quadrivalent influenza vaccine administered intramuscularly at a dose of 15 ug of HA per component, as approved by the FDA.
Outcomes
Primary Outcome Measures
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 Outcome Measures
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.
Assessment of the functionality 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. Functionality, defined by expression of specific cellular markers, will be measured by flow cytometry-based assays. Measurement of the functionality 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.
Assessment of B cell responses to influenza vaccination in individuals of different birth years
B cells will be assessed among PBMCs collected at baseline and after vaccination. Frequencies, defined by percent increase or decrease, and clonal expansion will be measured by flow cytometry-based and high-throughput DNA sequencing assays. These metrics will be compared among individuals of different birth years to determine the effect of year of birth on B cells responses following influenza vaccination.
Full Information
NCT ID
NCT05108818
First Posted
October 11, 2021
Last Updated
November 17, 2022
Sponsor
University of Pennsylvania
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Stanford University, The Scripps Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT05108818
Brief Title
Characterization of Humoral and Cellular Immune Responses Elicited by Influenza Vaccination in Healthy Adults
Official Title
Characterization of Humoral and Cellular Immune Responses Elicited by Influenza Vaccination in Healthy Adults
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 7, 2021 (Actual)
Primary Completion Date
April 2027 (Anticipated)
Study Completion Date
April 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Stanford University, The Scripps Research Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
The investigators and others have shown that the first influenza virus someone is exposed to leaves an immunological imprint that affects antibody responses to antigenically related influenza strains later in life. Year of birth can therefore be used to predict influenza virus exposures during the first years of life. It is possible that immune responses to influenza vaccination later in life differ between people with different birth years, depending on what virus someone was "imprinted" with. This could result in birth year differences in antibody responses upon vaccination and vaccine effectiveness. However, the effect of year of birth on the specificity of humoral and cellular immune responses elicited by influenza vaccination has not been studied in depth. In this study, the investigators will measure influenza virus cellular and humoral immune responses in individuals of different birth years before and after influenza vaccination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, Human
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
700 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Influenza vaccination
Arm Type
Experimental
Arm Description
Adults will receive a seasonal, inactivated, quadrivalent influenza vaccine administered intramuscularly at a dose of 15 ug of HA per component, as approved by the FDA.
Intervention Type
Biological
Intervention Name(s)
Seasonal influenza vaccine
Intervention Description
The seasonal influenza vaccine is administered intramuscularly at a dose of 15 ug of HA per component, as approved by the FDA.
Primary Outcome Measure Information:
Title
Effect of year of birth on neutralizing antibody titers elicited by influenza vaccination
Description
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.
Time Frame
7 years
Secondary Outcome Measure Information:
Title
Changes in serum HAI antibodies in individuals of different birth years following influenza vaccination
Description
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.
Time Frame
7 years
Title
Differences in levels of HA stalk-binding antibodies in individuals of different birth years following influenza vaccination
Description
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.
Time Frame
7 years
Title
Differences in levels of NA-binding antibodies in individuals of different birth years following influenza vaccination
Description
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.
Time Frame
7 years
Title
Assessment of the frequency of circulating T follicular helper cell response to influenza vaccination in individuals of different birth years
Description
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.
Time Frame
7 years
Title
Assessment of the functionality of circulating T follicular helper cell response to influenza vaccination in individuals of different birth years
Description
Circulating T follicular helper cells (cTfh) with be assessed among peripheral blood mononuclear cells (PBMCs) collected at baseline and after vaccination. Functionality, defined by expression of specific cellular markers, will be measured by flow cytometry-based assays. Measurement of the functionality 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.
Time Frame
7 years
Title
Assessment of B cell responses to influenza vaccination in individuals of different birth years
Description
B cells will be assessed among PBMCs collected at baseline and after vaccination. Frequencies, defined by percent increase or decrease, and clonal expansion will be measured by flow cytometry-based and high-throughput DNA sequencing assays. These metrics will be compared among individuals of different birth years to determine the effect of year of birth on B cells responses following influenza vaccination.
Time Frame
7 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Immunosuppression as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months
Treatment with immunoglobulin or another blood product within the 3 months prior to enrollment in this study
Active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematological malignancy ("active" is defined as having received treatment within the past 5 years)
Long-term (greater than 2 weeks) usage of oral or parenteral steroids, or high-dose inhaled steroids
Administration of an influenza vaccine within 2 months prior to enrollment
Known acute or chronic medical condition that, in the opinion of the investigator or appropriate sub-investigator, would render vaccination unsafe or would interfere with the evaluation of responses
Participation in a study that involves an experimental agent or having received an experimental agent (other than a COVID-19 vaccine) within 1 month prior to enrollment or expecting to receive another experimental agent during the study period
Intends to donate blood during the study period
Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol
Known human immunodeficiency virus, hepatitis B, or hepatitis C infection
Any condition that the principal investigator believes may interfere with successful completion of the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Scott Hensley, PhD
Phone
215-573-3756
Email
hensley@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Elizabeth Drapeau, PhD
Phone
215-573-3756
Email
elizabeth.troisi@pennmedicine.upenn.edu
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Drapeau, PhD
Email
elizabeth.troisi@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
Scott Hensley, PhD
Email
hensley@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
Scott Hensley, PhD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Protocol and statistical analysis plan may need to be shared for publication.
IPD Sharing Time Frame
At publication
IPD Sharing Access Criteria
Per journal publication policy
Learn more about this trial
Characterization of Humoral and Cellular Immune Responses Elicited by Influenza Vaccination in Healthy Adults
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