# Evaluation of pregnancy on vaccine-induced immunity and protection in a pre-clinical model of RSV infection

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2022 · $768,859

## Abstract

RSV is the leading cause of acute lower respiratory tract infections in children, causing an estimated 33 million
new infections each year. Despite this significant global burden, there is no RSV vaccine and there are currently
limited therapeutic options for severe RSV infection. Vaccine efforts have been hindered by 1) failure of early
vaccine attempts using formalin-inactivated RSV (FI-RSV) which led to the occurrence of enhanced respiratory
disease (ERD) in some infants and 2) deficiencies of rodent models that do not to recapitulate critical aspects of
human infant RSV infection. Studies have shown that vaccination with FI-RSV and subsequent RSV challenge
skews Th2-cell mediated responses towards immunopathology, while prior exposure to live virus properly primes
the adaptive and innate immune systems without ERD. Consequently, the potential for subunit and inactivated
RSV vaccines to cause ERD remains a particular concern for RSV naïve pediatric population. In this proposal,
we offer a novel immunization strategy in a highly relevant, pre-clinical model of RSV that addresses these
barriers to vaccine development. We propose to test novel maternal immunization strategies for eliciting
protective maternal immunity and test the protective efficacy of passive transfer of neutralizing antibodies. We
hypothesize that this approach will provide protective passive immunity in infants during perinatal period of
greatest RSV susceptibility. We propose to test this approach in a non-human primate model of RSV infection
using recombinant virus-like particle (VLP) vaccines expressing F antigen in appropriate conformation. In
addition, we will use this immunization strategy to improve understanding of critical aspects of maternal
immunization including 1) the effects of pregnancy on vaccine-induced immunity 2) the kinetics of maternal
transfer of neutralizing antibodies responses and 3) the efficacy of maternal immunization and protection in a
clinically relevant infant primate model. In addition, we will define innate and adaptive immune correlates of
protection in RSV infection in adult macaques, information that will be critical to the understanding of deficiencies
in the infant lung environment. We expect these studies will have a catalytic effect on the RSV field by
establishing a pre-clinical model of infection for design and testing maternal immunization strategies as well as in
a highly relevant, pre-clinical model that most closely mimics human disease.

## Key facts

- **NIH application ID:** 10470252
- **Project number:** 5R01AI141648-03
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Karen A Norris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $768,859
- **Award type:** 5
- **Project period:** 2020-09-24 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470252

## Citation

> US National Institutes of Health, RePORTER application 10470252, Evaluation of pregnancy on vaccine-induced immunity and protection in a pre-clinical model of RSV infection (5R01AI141648-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10470252. Licensed CC0.

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