# Sex differences in immune responses to vaccine and circulating strains of influenza in healthcare workers

> **NIH NIH U54** · JOHNS HOPKINS UNIVERSITY · 2020 · $308,576

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Klein, Sabra L.
PROJECT II: Sex differences in immune responses to vaccine and circulating strains of influenza in
healthcare workers
Summary
Seasonal epidemics of influenza pose important public health threats to humans despite the
availability of vaccines and antivirals. Influenza vaccine efficacy can vary significantly from year to
year and the immunogenicity of the vaccine or the antigenic match between the vaccine and
circulating influenza strains are most often blamed for the low efficacy. However, host factors,
including the sex and age of the vaccine, may also be contributing to poor influenza vaccine efficacy
but these have not been explored extensively. Adult females often have stronger antibody responses
to a number of antigens – including influenza vaccines - when compared to males. These differences
are often most pronounced during their reproductive years when sex hormone levels are highest. Our
preliminary data illustrate that females (18-45 years of age) develop higher neutralizing antibody titers
to a vaccine antigen, but not to a antigenic variant virus, which may reflect the greater specificity of
the female’s antibody response. The SADII Research Project 2 will investigate sex differences in
response to influenza vaccination in a human cohort of individuals between the ages of 18-45. We will
quantify sex differences in pre-existing immunity to influenza, as this may contribute to the magnitude
of the sex differences after vaccination. We will characterize sex-specific differences, with
consideration of hormonal and genetic mediators, in a number of different antibody responses,
including virus neutralizing activity, antibody avidity, and IgG class switch recombination. The number
of total and antigen-specific B cells will be determined and the transcriptional activity and B cell
receptor utilization of the antibody producing B cells will be quantified. Together, the studies in the
SADII Research Project 2 will enhance our understanding of the role of sex in modulating the immune
response to influenza vaccination and identify sex-specific mechanisms mediating those differences
in adults. If females of reproductive ages develop antibody and memory B cell responses that are of
greater titer and specificity than males, then this should inform the formulation, dosing, and predicted
protection following vaccination, in a manner similar to our consideration of age in vaccination
guidelines.
OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page

## Key facts

- **NIH application ID:** 9939399
- **Project number:** 5U54AG062333-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Andrew S. Pekosz
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $308,576
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939399

## Citation

> US National Institutes of Health, RePORTER application 9939399, Sex differences in immune responses to vaccine and circulating strains of influenza in healthcare workers (5U54AG062333-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9939399. Licensed CC0.

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