Immunogenicity and Protective Efficacy of DNA Vaccines Expressing Rhesus Cytomegalovirus Glycoprotein B, Phosphoprotein 65-2, and Viral Interleukin-10 in Rhesus Macaques
http://jvi.asm.org/cgi/content/abstract/81/3/1095
Yujuan Yue,<SUP>1</SUP><SUP>*</SUP> Amitinder Kaur,<SUP>6</SUP> Meghan K. Eberhardt,<SUP>1</SUP> Nadine Kassis,<SUP>6</SUP> Shan Shan Zhou,<SUP>1</SUP> Alice F. Tarantal,<SUP>2</SUP><SUP>,3</SUP><SUP>,4</SUP> and Peter A. Barry<SUP>1</SUP><SUP>,2</SUP><SUP>,5</SUP>
<SUP></SUP>
http://jvi.asm.org/cgi/content/abstract/81/3/1095
Yujuan Yue,<SUP>1</SUP><SUP>*</SUP> Amitinder Kaur,<SUP>6</SUP> Meghan K. Eberhardt,<SUP>1</SUP> Nadine Kassis,<SUP>6</SUP> Shan Shan Zhou,<SUP>1</SUP> Alice F. Tarantal,<SUP>2</SUP><SUP>,3</SUP><SUP>,4</SUP> and Peter A. Barry<SUP>1</SUP><SUP>,2</SUP><SUP>,5</SUP>
<SUP></SUP>
Center for Comparative Medicine,<SUP>1</SUP> California National Primate Research Center,<SUP>2</SUP> Departments of Pediatrics,<SUP>3</SUP> Cell Biology and Human Anatomy,<SUP>4</SUP> Pathology and Laboratory Medicine, University of California, Davis, California,<SUP>5</SUP> New England National Primate Research Center, Harvard University, Southborough, Massachusetts<SUP>6</SUP>
Rhesus cytomegalovirus (RhCMV) infection of macaques exhibits<SUP> </SUP>strong similarities to human CMV (HCMV) persistence and pathogenesis.<SUP> </SUP>The immunogenicity of DNA vaccines encoding three RhCMV proteins<SUP> </SUP>(a truncated version of glycoprotein B lacking the transmembrane<SUP> </SUP>region and endodomain [gB
TM], phosphoprotein 65-2 [pp65-2],<SUP> </SUP>and viral interleukin-10 [vIL-10]) was evaluated in rhesus macaques.<SUP> </SUP>
Two groups of monkeys (four per group) were genetically immunized<SUP> </SUP>four times with a mixture of either pp65-2 and gB
TM or pp65-2,<SUP> </SUP>vIL-10, and gB
TM. The vaccinees developed anti-gB and anti-pp65-2<SUP> </SUP>antibodies in addition to pp65-2 cellular responses after the<SUP> </SUP>second booster immunization, with rapid responses observed with<SUP> </SUP>subsequent DNA injections. Weak vIL-10 immune responses were<SUP> </SUP>detected in two of the four immunized animals.
Neutralizing<SUP> </SUP>antibodies were detected in seven monkeys, although titers were<SUP> </SUP>weak compared to those observed in naturally infected animals.<SUP> </SUP>The immunized monkeys and na?ve controls were challenged<SUP> </SUP>intravenously with 10<SUP>5</SUP> PFU of RhCMV. Anamnestic binding and<SUP> </SUP>neutralizing antibody responses were observed 1 week postchallenge<SUP> </SUP>in the vaccinees.
DNA vaccination-induced immune responses significantly<SUP> </SUP>decreased peak viral loads in the immunized animals compared<SUP> </SUP>to those in the controls.
No difference in peak viral loads<SUP> </SUP>was observed between the pp65-2/gB
TM DNA- and pp65-2/vIL-10/gB
TM-vaccinated<SUP> </SUP>groups. Antibody responses to nonvaccine antigens were lower<SUP> </SUP>postchallenge in both vaccine groups than in the controls, suggesting<SUP> </SUP>long-term control of RhCMV protein expression.
These data demonstrated<SUP> </SUP>that DNA vaccines targeting the RhCMV homologues of HCMV gB<SUP> </SUP>and pp65 altered the course of acute and persistent RhCMV infection<SUP> </SUP>in a primate host.<SUP> </SUP>

Two groups of monkeys (four per group) were genetically immunized<SUP> </SUP>four times with a mixture of either pp65-2 and gB


Neutralizing<SUP> </SUP>antibodies were detected in seven monkeys, although titers were<SUP> </SUP>weak compared to those observed in naturally infected animals.<SUP> </SUP>The immunized monkeys and na?ve controls were challenged<SUP> </SUP>intravenously with 10<SUP>5</SUP> PFU of RhCMV. Anamnestic binding and<SUP> </SUP>neutralizing antibody responses were observed 1 week postchallenge<SUP> </SUP>in the vaccinees.
DNA vaccination-induced immune responses significantly<SUP> </SUP>decreased peak viral loads in the immunized animals compared<SUP> </SUP>to those in the controls.
No difference in peak viral loads<SUP> </SUP>was observed between the pp65-2/gB


These data demonstrated<SUP> </SUP>that DNA vaccines targeting the RhCMV homologues of HCMV gB<SUP> </SUP>and pp65 altered the course of acute and persistent RhCMV infection<SUP> </SUP>in a primate host.<SUP> </SUP>