# THE IMPACT OF ADVANCED AGE AND SEX ON HUMORAL IMMUNITY TO STREPTOCOCCUS PNEUMONIAE

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $525,170

## Abstract

PROPOSAL SUMMARY/ABSTRACT
Streptococcus pneumoniae is estimated to cause over 1.6 million deaths/year worldwide. Pneumococcal disease
and related deaths are much more frequent in the elderly. The growing emergence of antibiotic-resistant S.
pneumoniae strains places increasing reliance on effective pneumococcal vaccines to protect this at-risk
population. The native pneumococcal vaccine currently used in adults consists of capsular polysaccharides
(PPS) derived from 23 different serotypes and therefore provides broad coverage against invasive disease with
an estimated efficacy of ~65-70%. Nonetheless, protection eventually wanes as antibody titers diminish,
typically by 5-10 years post-immunization, and protection against pneumonia is limited. Optimizing protective
vaccine responses in the elderly is therefore a major goal. However, in humans there are clear differences
between elderly males and females with respect to humoral responses to pneumococcal polysaccharide
antigens. We have found the same to be true in mice. The cause of these differences has gone uninvestigated
and therefore highlights a significant gap in our understanding of how sex-related differences impact humoral
immunity in the aged. Given the continued burden of pneumococcal disease in the elderly, an investigation of
the underlying factors contributing to altered immunity to S. pneumoniae with a strong consideration for sex
bias is long overdue. Three specific aims are designed to probe factors regulating B cell immunity to
pneumococcal polysaccharides and phosphorylcholine (PC) in aged males and females. In Aim 1, we will
determine the extent to which age and sex hormones impact the development, phenotype, and functional
responses of B-1b cells and PPS3-specific B cells. In Aim 2, we will investigate the mechanisms contributing to
altered PC-specific B cell populations and natural antibody secretion between aged males and females and
examine the consequences these alterations have for protection against pneumococcal infections. In Aim 3, we
will investigate the extent to which sex-driven differences impact protective mucosal responses to S.
pneumoniae. Our studies will thereby investigate the extent to which biological sex and gender-influencing
hormones intersect to impact the regulation of protective pneumococcal immunity throughout the lifespan.
Our results are expected to have a significant impact on the future design and administration of sex- and age-
appropriate vaccines, as well as promote informed decision-making for patients receiving hormone
replacement or gender-affirming therapy, such that optimal protection against pneumococcal infections can be
achieved.

## Key facts

- **NIH application ID:** 10914883
- **Project number:** 5R01AI164489-03
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Karen M Haas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $525,170
- **Award type:** 5
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914883

## Citation

> US National Institutes of Health, RePORTER application 10914883, THE IMPACT OF ADVANCED AGE AND SEX ON HUMORAL IMMUNITY TO STREPTOCOCCUS PNEUMONIAE (5R01AI164489-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10914883. Licensed CC0.

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