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.
Bibliographical noteFunding 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 2009 Elsevier B.V., All rights reserved.
- Animal models
- Congenital cytomegalovirus infection
- Cytomegalovirus vaccines
- Guinea pig cytomegalovirus
- MHC class I homolog
- Viral immune evasion