# CMV pentameric complex based vaccine strategies for prevention of congenital CMV

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2020 · $308,138

## Abstract

Abstract
Development of a cytomegalovirus (CMV) vaccine is a major public health priority due to the risk of congenital
infection. Clinical strains of human CMV (HCMV) differ from lab adapted virus as the clinical strains express a
pentameric complex (PC) and retain the ability to infect epithelial and endothelial cells unlike lab strains which
are limited to fibroblast cells. The mechanism of virus entry into epi/endothelial cells is different from the gB
pathway of entry into fibroblast cells as it requires viral proteins gH/gL/UL128-131 forming an endocytic
complex (PC) to enable viral cell entry. Importantly, transplacental CMV infection is highly dependent upon
viral epithelial/endothelial tropism since the virus has to infect endothelial cells of blood vessels (maternal and
fetal) as well as a layer of epithelial trophoplast cells that constitute part of the placenta. Neutralizing antibodies
to the PC are potentially more important than antibodies to the immunodominant gB glycoprotein, since anti-
PC antibodies are more effective in neutralizing virus on epi/endothelial cells compared to gB. Importantly, in
convalescent patients high anti-PC titers are thought to be effective in preventing congenital CMV. Human
CMV cannot be directly studied in an animal model because of species specificity. The guinea pig is the only
small animal model that allows the study of congenital CMV but requires the use of species specific guinea pig
CMV (GPCMV). In the guinea pig model for congenital CMV, we have defined a homolog pentameric complex
as necessary for epithelial tropism, virus dissemination and congenital infection by GPCMV. Furthermore, the
GPCMV homolog PC is highly immunogenic and generates antibodies that neutralize virus infection on
epithelial cells. This pre-clinical translational study seeks to develop GPCMV PC specific vaccine strategies
(either subunit or defective adenovirus vector based) to determine if a PC or PC subcomplex vaccine strategy
can prevent congenital CMV in the guinea pig model. Importantly, as part of these studies we will evaluate the
ability of PC vaccines to cross protect against congenital CMV from different GPCMV strains. Additionally, the
synergy effect of gB and PC vaccine strategies will be evaluated. Finally, since in HCMV both gB and gH
induce a CD4 T cell response, the protective impact of the T cell response will be evaluated.

## Key facts

- **NIH application ID:** 9931240
- **Project number:** 5R01HD090065-04
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** ALISTAIR MCGREGOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $308,138
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931240

## Citation

> US National Institutes of Health, RePORTER application 9931240, CMV pentameric complex based vaccine strategies for prevention of congenital CMV (5R01HD090065-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9931240. Licensed CC0.

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