# Development of a universal DISC vaccine strategy against congenital cytomegalovirus

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2021 · $649,911

## Abstract

ABSTRACT
Congenital CMV (cCMV) is a leading cause of hearing loss and cognitive impairment in surviving newborns. A
vaccine is a high priority but an effective vaccine needs to exceed protection levels of natural convalescent
immunity because of the risk of re-infection by multiple strains of HCMV. The guinea pig is the only small
animal model for cCMV with disease in pups similar to humans. Previously it was demonstrated that guinea pig
cytomegalovirus (GPCMV) encodes functionally similar essential viral glycoprotein complexes to HCMV, which
can act as neutralizing antibody target antigens. An important correlation with HCMV is that GPCMV encodes
a functional gH based pentamer complex (PC) necessary for virus tropism/entry to non-fibroblast cells,
pathogenesis and cCMV. Previously, the efficacy of two non-replication competent capsid mutant GPCMV
DISC (Defective Infectious Single Cycle) vaccine strains were evaluated: (1) lacking PC (DISCI); (2) encoding
PC (DISCII). DISCII was more successful in neutralizing virus on epithelial cells and fully protected against
cCMV when pregnant animals were challenged with wild type virus. However, a significant challenge that
remains to be attained is the ability of a DISC vaccine strategy to protect against: (1) multistrain virus
challenge, which is an absolute necessity for a successful HCMV vaccine; (2) provide protection against
natural routes of infection. A newly isolated GPCMV strain (CRV) will be included in the studies to enable
multistrain virus challenge. Modified GPCMV DISC vaccine strain will be improved for immunogenicity and
correlates of immune protection determined. An important leap in the guinea pig model studies is that we will
employ the first gene knockout (IFNLR1) guinea pig to evaluate the importance of IFN III in shaping immune
response. The overall central hypothesis is that the DISC vaccine strategy can provide greater protection
against cCMV compared to convalescent immunity and can fully protect against multiple strains of virus and
natural routes of infection but vaccine requires comprehensive CMV gene expression that is potentially lacking
in IE1 mutant based DISC vaccine strains. The proposed studies will provide an accelerated timeline for the
realistic evaluation of a DISC vaccine strategy against cCMV.

## Key facts

- **NIH application ID:** 10096812
- **Project number:** 1R01AI155561-01
- **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:** 2021
- **Award amount:** $649,911
- **Award type:** 1
- **Project period:** 2021-04-07 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10096812

## Citation

> US National Institutes of Health, RePORTER application 10096812, Development of a universal DISC vaccine strategy against congenital cytomegalovirus (1R01AI155561-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10096812. Licensed CC0.

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