# Immunologic strategies to prevent congenital cytomegalovirus transmission and disease in rhesus monkeys

> **NIH NIH P01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $4,199,924

## Abstract

ABSTRACT - OVERALL
Congenital cytomegalovirus (cCMV) is a prevalent in utero infection, affecting approximately 1 in 200 newborns
and leading to severe neurological impairment in 1 in 5 infected infants. Maternal CMV-specific adaptive
immunity is partially protective against cCMV infection, with reduced transmission rates observed in
chronically-infected women upon reinfection. However, challenges in CMV vaccine development include
limited understanding of viral and immunological factors involved in cCMV transmission, strategies to
counteract immune evasion mechanisms, and critical vaccine antigen targets. To address these challenges,
our team developed and refined a nonhuman primate (NHP) model of cCMV infection in rhesus monkeys,
which we demonstrated to closely mimic human transmission and fetal disease rates in our initial cycle of this
P01 Program. Surprisingly, immune responses following maternal infection did not predict transmission risk,
suggesting the need for pre-existing immunity different from natural infection. The NHP model also revealed T
cell trafficking to the maternal-fetal interface following maternal CMV infection, the limited role of the viral
pentameric glycoprotein complex in cCMV transmission, the role of Fc-mediated antibody responses in CMV
containment, and viral immune evasion mechanisms as important factors in reducing CMV dissemination.
Traditional vaccine approaches focused on neutralizing antibodies may be insufficient, prompting the
evaluation of novel CMV vaccine candidates in the NHP model. We hypothesize that disarming the virus by
eliciting immunity against key viral immune evasions and inducing cellular immunity at the maternal-fetal
interface will prevent cCMV transmission following primary infection during pregnancy. The studies proposed in
the renewal of this P01 Program will assess the role of CD8+ T cell responses at the maternal-fetal interface in
preventing cCMV transmission (Project 1), the impact of vaccine-induced immunity against viral immune
evasions, such as UL146 chemokine homologs (Project 2) and viral Fc receptors (Project 3), and test three
novel vaccines targeting each of these novel immune mechanisms. The Program's ultimate goal is to develop
an effective CMV vaccine, considering the limitations of previous approaches and targeting immune evasion
proteins while eliciting local immunity at the maternal-fetal interface. The research will employ NHP models,
placental organoid models, viral engineering, sequence analysis, and bioinformatics to de-risk these vaccine
concepts before advancing to human efficacy trials. The successful development of a CMV vaccine is crucial
for eliminating the most common infectious cause of birth defects and brain damage worldwide.

## Key facts

- **NIH application ID:** 10874233
- **Project number:** 2P01AI129859-07
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Sallie R. Permar
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $4,199,924
- **Award type:** 2
- **Project period:** 2019-07-24 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874233

## Citation

> US National Institutes of Health, RePORTER application 10874233, Immunologic strategies to prevent congenital cytomegalovirus transmission and disease in rhesus monkeys (2P01AI129859-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10874233. Licensed CC0.

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