# Protective antibody in streptococcal infection models

> **NIH NIH R01** · NEW YORK MEDICAL COLLEGE · 2024 · $599,556

## Abstract

ABSTRACT
The initial contact between newly transmitted group A streptococci (GAS) and its human host can be readily
thwarted by antibody (Ab) directed to the appropriate GAS antigens (Ags). To best simulate this
microenvironment, physiological (i.e., low) inoculum doses of GAS are essential. The goal of this proposal is to
identify Ags, alone and in combinations representing multicomponent vaccines, that are the most effective
targets of Ab-mediated immunity and collectively can provide worldwide coverage against all GAS strains.
The underlying rationale for the proposed approach rests on two principles: That serum obtained from children
just prior to a new GAS infection lacks protective Ab, and that serum obtained from most adults has at least
low levels of persisting protective Ab. The latter is based on the very low incidence of GAS infection in adults,
likely the result of protective immunity that developed following repeated infections earlier in life. Hypotheses
on protective Ag-specific Ab generated from analysis of pediatric serum (aim 1) are experimentally tested in
mice (aim 2). Pre-infection pediatric serum is analyzed for lack of protective Ab to leading vaccine candidates.
Adult serum is used as a source for purified immunoglobulin (Ig) specific to the vaccine target Ags missing in
susceptible children. Immunodeficient mice are passively immunized with the Ag-specific Ig purified from adults
and challenged with low infective doses of GAS. The Ag-specific Ig that confers protection in mice equates to a
human serum-based correlate of protection (CoP).
Four major forms of GAS disease are modeled in mice and evaluated for protective immunity: upper
respiratory tract infection, impetigo, skin and soft tissue infection and invasive disease. GAS from all three
major subpopulations of strains are tested: throat specialists, skin specialists and generalists. The Ag targets
evaluated are leading vaccine candidates and include broadly and semi-conserved Ags as well as surface and
secreted Ags. If successful, this work will identify a collection of Ag targets that can serve as the basis for
global protection. It will also deliver two new standardized platforms – screening of pre-infection human serum
Ab to GAS Ags and improved mouse models - for future identification and straightforward comparison of
additional GAS vaccine candidates.

## Key facts

- **NIH application ID:** 10747980
- **Project number:** 5R01AI173565-02
- **Recipient organization:** NEW YORK MEDICAL COLLEGE
- **Principal Investigator:** Debra E BESSEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $599,556
- **Award type:** 5
- **Project period:** 2022-12-02 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747980

## Citation

> US National Institutes of Health, RePORTER application 10747980, Protective antibody in streptococcal infection models (5R01AI173565-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10747980. Licensed CC0.

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