# Project 1:  Immune correlates of cCMV

> **NIH NIH P01** · DUKE UNIVERSITY · 2020 · $1,914

## Abstract

Abstract – Project 1: Immune correlates of protection against congenital CMV
Cytomegalovirus is the most common congenital infection, complicating 40,000 births in the U.S. annually. Up
to 25% of infants born with CMV will have permanent neurologic disabilities, including hearing loss.
Development of a maternal vaccine that induces effective preconception immunity offers the best hope of
eliminating congenital CMV (cCMV), yet this strategy faces significant hurdles. Among these are the
incomplete protection conferred by natural immunity and an incomplete understanding of what constitutes
protective CMV immunity. While CMV-seropositive mothers have a reduced risk of vertical CMV transmission
upon reinfection compared to CMV-naïve mothers with primary infection during pregnancy, they can still
transmit virus. Because natural immunity is only partially protective, an effective vaccine will need to induce
a more robust or modified preconception immune response. To investigate immune protection against
cCMV, we established a novel nonhuman primate (NHP) model of placental cCMV transmission in rhesus
monkeys, and showed that maternal CD4+ T cell responses are critical in protection. A lag in the development
of CMV-neutralizing antibodies and cytotoxic T lymphocytes was associated with a more severe outcome; and
passive infusion of CMV seronegative dams with hyperimmune globulin prior to rhesus CMV inoculation
protected against fetal loss. Although these studies highlight the importance of maternal immunity, the
contribution of individual arms of the immune system in preventing cCMV remains unclear. Project 1 will
therefore test the hypothesis that both humoral and cellular maternal CMV-specific immune responses are
required to prevent cCMV infection. Defining the precise contribution of individual components of anti-CMV
immunity to (i) inhibition of placental transmission and (ii) modulation of fetal disease is necessary to determine
whether CMV vaccines should target one or both arms of the adaptive immune system. In concert with Cores
1-4, Project 1 will use a combination of genetic analysis, in vivo depletion experiments, and exhaustive
immune and virologic evaluation to characterize transmitted virus variants and determine the contribution of
CMV-specific humoral and cellular immune responses in protecting against cCMV in the NHP model. Our
specific aims are as follows: Aim 1: Characterize placental CMV transmission during primary infection in
immunocompetent dams and define maternal and fetal immune correlates of protection against transmission;
Aim 2: Determine the contribution of B and CD8+ T cell immunity to protection against placental CMV
transmission; Aim 3: Determine whether vaccine-induced pre-conception T cell immunity is sufficient to lower
plasma viremia and protect against placental CMV transmission or fetal loss in primary infection. These studies
will provide insight in to the correlates of immune protection against placental CMV tra...

## Key facts

- **NIH application ID:** 10215784
- **Project number:** 3P01AI129859-02S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Sallie R. Permar
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,914
- **Award type:** 3
- **Project period:** 2019-07-24 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215784

## Citation

> US National Institutes of Health, RePORTER application 10215784, Project 1:  Immune correlates of cCMV (3P01AI129859-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10215784. Licensed CC0.

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