# Identifying and modeling immune correlates of protection against congenital CMV transmission after primary maternal infection

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $822,260

## Abstract

ABSTRACT
Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of birth defects and brain damage
worldwide, leaving >5,000 infants with permanent disabilities each year in the U.S. alone, with a
disproportionate proportion in minority populations. While a vaccine to prevent cCMV has been labeled “tier 1
priority” for over 20 years, we remain without a licensed vaccine product, in part due to limited understanding of
the types of immune responses that are protective against placental CMV transmission. Primary infection
during pregnancy is high risk for cCMV transmission, yet only approximately a third of mothers acutely-infected
during pregnancy will transmit the virus to their infants, suggesting that the rapidity and magnitude of the
maternal immune responses plays a role in protection against placental virus transmission. The overarching
goal of this proposal is to define CMV-specific humoral and cellular immune responses associated with
reduced risk of fetal transmission and model their impact on placental transmission. To address this goal, we
have access to a unique cohort of 399 acutely CMV-infected transmitting and non-transmitting pregnant
women enrolled in the NIH National Institute of Child Health and Human Development (NICHD) Maternal Fetal
Medicine Unit (MFMU) CMV hyperimmunoglobulin trial (NCT01376778). This trial was a double-blind
randomized trial that screened >100,000 pregnant women for acute CMV infection for enrollment to receive
either CMV hyperimmunoglobulin (HIG) or placebo, yet was stopped for futility, creating a unique opportunity to
define the acute cellular and humoral immune responses that are associated with transmission risk since HIG
infusion after seroconversion did not change transmission risk. Our hypothesis is that the combination of
early, functional CMV-specific IgG responses and CD4+ T cell and specialized innate immune cell responses
to primary CMV infection during pregnancy will predict reduced risk of fetal transmission and disease. The
combined strength of this uniquely large acutely CMV-infected pregnant cohort, our expertise in measuring
CMV-specific humoral and cellular immune responses, and expertise in novel mathematical and placental
organoid models will inform immune targets of CMV vaccine development that will be predicted to reduce the
risk of cCMV transmission. Our Specific Aims include: 1) Define the CMV-specific IgG binding and functional
responses associated with reduced transmission and disease following primary CMV infection in pregnancy; 2)
Define the cellular immune responses elicited during primary CMV infection that associate with reduced
transmission in pregnancy; 3) Develop an in silico model that can predict candidate CMV vaccine efficacy for
prevention of placental transmission based on maternal immune correlates of cCMV transmission and the rate
of viral spread in placental organoid models. Defining immune targets that will reduce fetal transmission and
infant...

## Key facts

- **NIH application ID:** 10811776
- **Project number:** 5R01AI173333-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Sallie R. Permar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $822,260
- **Award type:** 5
- **Project period:** 2023-03-17 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811776

## Citation

> US National Institutes of Health, RePORTER application 10811776, Identifying and modeling immune correlates of protection against congenital CMV transmission after primary maternal infection (5R01AI173333-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10811776. Licensed CC0.

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