A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection

Megan M. Crumpler; K. Yeon Choi; Michael A. McVoy; Mark R. Schleiss

doi:10.1016/j.vaccine.2009.04.036

A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection

Megan M. Crumpler, K. Yeon Choi, Michael A. McVoy, Mark R. Schleiss

Pediatrics - Infectious Disease

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Live attenuated vaccines for prevention of congenital cytomegalovirus infections encode numerous immune evasion genes. Their removal could potentially improve vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC class I homologs (presumed NK evasins) were deleted from the guinea pig cytomegalovirus genome and the resulting virus, 3DX, was evaluated as a live attenuated vaccine in the guinea pig congenital infection model. 3DX was attenuated in vivo but not in vitro. Vaccination with 3DX produced elevated cytokine levels and higher antibody titers than wild type (WT) virus while avidity and neutralizing titers were similar. Protection, assessed by maternal viral loads and pup mortality following pathogenic viral challenge during pregnancy, was comparable between 3DX and WT and significant compared to naïve animals. These results suggest that the safety and perhaps efficacy of live attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral immunomodulatory genes.

Original language	English (US)
Pages (from-to)	4209-4218
Number of pages	10
Journal	Vaccine
Volume	27
Issue number	31
DOIs	https://doi.org/10.1016/j.vaccine.2009.04.036
State	Published - Jun 24 2009

Bibliographical note

Funding Information:
The authors are grateful to Dong Yu for providing plasmid pYD-Tn1721, to Søren Warming for providing SW102 E. coli cells, and to Jodi Anderson and Michael Leviton for their technical assistance. We also thank Julie McVoy for providing the Excel program used for curve fitting and IC 50 determinations. This work was supported by grants R01HD044864 and R01HD038416 from the National Institutes of Health.

Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.

Keywords

Animal models
Congenital cytomegalovirus infection
Cytomegalovirus vaccines
Guinea pig cytomegalovirus
MHC class I homolog
Viral immune evasion

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10.1016/j.vaccine.2009.04.036

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A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection. / Crumpler, Megan M.; Choi, K. Yeon; McVoy, Michael A. et al.
In: Vaccine, Vol. 27, No. 31, 24.06.2009, p. 4209-4218.

Research output: Contribution to journal › Article › peer-review

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abstract = "Live attenuated vaccines for prevention of congenital cytomegalovirus infections encode numerous immune evasion genes. Their removal could potentially improve vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC class I homologs (presumed NK evasins) were deleted from the guinea pig cytomegalovirus genome and the resulting virus, 3DX, was evaluated as a live attenuated vaccine in the guinea pig congenital infection model. 3DX was attenuated in vivo but not in vitro. Vaccination with 3DX produced elevated cytokine levels and higher antibody titers than wild type (WT) virus while avidity and neutralizing titers were similar. Protection, assessed by maternal viral loads and pup mortality following pathogenic viral challenge during pregnancy, was comparable between 3DX and WT and significant compared to na{\"i}ve animals. These results suggest that the safety and perhaps efficacy of live attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral immunomodulatory genes.",

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A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection

Abstract

Bibliographical note

Keywords

UN SDGs

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