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.
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.
Crumpler
Megan M
MM
Department of Microbiology & Immunology, Virginia Commonwealth University, Richmond, VA, USA.
Choi
K Yeon
KY
McVoy
Michael A
MA
Schleiss
Mark R
MR
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D022482:Cytomegalovirus Vaccines / Q000235:genetics / Q000276:immunology*; D005260:Female; D017353:Gene Deletion; D006168:Guinea Pigs; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011247:Pregnancy; D019211:Roseolovirus / Q000235:genetics / Q000276:immunology*; D016415:Sequence Alignment; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics*
D000914:Antibodies, Viral; D016207:Cytokines; D022482:Cytomegalovirus Vaccines; D014613:Vaccines, Attenuated; D014764:Viral Proteins; D037521:Virulence Factors