# Sex differences in the impact of frailty on vaccine-induced immune responses in community-dwelling older adults

> **NIH NIH U54** · JOHNS HOPKINS UNIVERSITY · 2020 · $328,228

## Abstract

SADII RESEARCH PROJECT 1 SUMMARY
Influenza is an ongoing threat to human health. It challenges the aging immune system every
year and causes the highest burden of severe disease and complications in older Americans,
particularly those who are older and frail. Annual vaccination remains the main stay of influenza
prevention. While efforts to improve vaccine antigenicity are important with certain level of
success, it is paramount to address host factors that impact immune responses to the vaccine,
as well. We and others have observed vaccine failure in providing acceptable humoral immunity
or clinical protection for the frail elderly, indicating the impact of aging and frailty. However, the
impact of sex and gender on vaccine-induced humoral immunity and adverse reactions in these
vulnerable individuals. Particularly in the context of repeated annual vaccination has not been
adequately evaluated. Our ongoing R01-funded 5-year influenza immunization study is targeted
to adults over 75 years of age with 125 subjects participated in at least two years (54 males,
43.2%). Preliminary analyses of hemagglutination inhibition titers from the 2015-16 flu season
reveal that females were more likely to seroconvert to all vaccine flu strains than males, but
these differences were dependent on both age and race. This project builds on the longitudinal
component of the ongoing study and proposes an 8-yr longitudinal investigation focusing on!sex
differences in vaccine-induced immunity against flu in the frail elderly, with consideration of the
intersection of sex and gender with other social stratifiers. It proposes the following aims: 1) to
characterize sex differences in antibody responses (NT, HI, ELISA, antibody avidity and IgG
subtype) to influenza antigens (HA, NA and M2) and adverse reactions to the annual
vaccinations; 2) to characterize sex differences in B cell responses (composition and numbers
of memory cells, plasmablasts, and age-associated B cells) specific to HA, NA and M2 to the
annual vaccinations; and 3) to explore sex differences in transcriptional activation and B-cell
repertoire utilization in response to the annual vaccination. Delineating the impact of sex and
gender as important host factors longitudinally in the context of aging, frailty and repeated
annual vaccination will shed light on the mechanisms underlying sex-specific vulnerability and
facilitate the development of more effective influenza immunization strategy for the most
vulnerable older adults.

## Key facts

- **NIH application ID:** 9939397
- **Project number:** 5U54AG062333-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Sean Xiao Leng
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $328,228
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939397

## Citation

> US National Institutes of Health, RePORTER application 9939397, Sex differences in the impact of frailty on vaccine-induced immune responses in community-dwelling older adults (5U54AG062333-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9939397. Licensed CC0.

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