# Humoral immune correlates of protection against congenital CMV and HSV transmission in HIV-infected women

> **NIH NIH R21** · DUKE UNIVERSITY · 2020 · $29,470

## Abstract

ABSTRACT
While the use of antiretroviral therapy (ART) to treat HIV-1-infected mothers has reduced the
rate of mother-to-child transmission (MTCT) of HIV, HIV-exposed, uninfected (HEU) infants still
face numerous health risks, including risk of mortality, developmental deficits, and severe
infections. In particular, HEU infants face increased susceptibility to perinatal viral infections
including congenital cytomegalovirus (CMV) and neonatal herpes simplex virus (HSV).
Congenital CMV infection is a leading cause of sensorineural hearing loss and permanent
neurologic deficits, and neonatal HSV-1/2 can result in severe sepsis, devastating neurological
deficits, and death. Thus, there is significant need to protect HIV-exposed infants against these
viruses, including the development of prophylactic and treatment strategies for HSV and CMV.
Currently, the primary causes for this increased risk of perinatal herpes virus infections in HEU
infants remain unexplored. We hypothesize that (1) HIV-infected mothers have impaired
HSV/CMV-specific IgG responses, including protective antiviral functions such as antibody-
dependent cellular cytotoxicity (ADCC), antibody-dependent cell phagocytosis (ADCP), and
virus neutralization and (2) in the context of HIV, these maternal antibodies are variably
transplacentally transferred to the infant, leaving HEU infants at higher risk for severe perinatal
infections.
This study aims to define the placental transmission rate of and characteristics of CMV and
HSV-specific IgG in HIV-infected pregnant women and their infants. Furthermore, this study will
define the humoral immune correlates of protection against congenital CMV transmission. The
investigation of maternal antibodies will include the identification of Fc region characteristics
associated with efficient placental IgG transfer and assessment of the role of antiviral antibody
functions in perinatal virus transmission, including neutralization, ADCC, and ADCP. This work
will establish the immunologic basis for increased risk for CMV and HSV infections in HEU
infants, and importantly, will provide insight into rational vaccine design to ultimately reduce the
risk and severity of congenital CMV and neonatal HSV infections for all children.

## Key facts

- **NIH application ID:** 9970410
- **Project number:** 5R21AI147992-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** BRENNA L. HUGHES
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $29,470
- **Award type:** 5
- **Project period:** 2019-07-03 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970410

## Citation

> US National Institutes of Health, RePORTER application 9970410, Humoral immune correlates of protection against congenital CMV and HSV transmission in HIV-infected women (5R21AI147992-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9970410. Licensed CC0.

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