Immunogenicity and Protective Efficacy of DNA Vaccines Expressing Rhesus Cytomegalovi

Snowy Owl · Jan 19, 2007

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,1* Amitinder Kaur,6 Meghan K. Eberhardt,1 Nadine Kassis,6 Shan Shan Zhou,1 Alice F. Tarantal,2,3,4 and Peter A. Barry1,2,5


Center for Comparative Medicine,1 California National Primate Research Center,2 Departments of Pediatrics,3 Cell Biology and Human Anatomy,4 Pathology and Laboratory Medicine, University of California, Davis, California,5 New England National Primate Research Center, Harvard University, Southborough, Massachusetts6

Rhesus cytomegalovirus (RhCMV) infection of macaques exhibits strong similarities to human CMV (HCMV) persistence and pathogenesis. The immunogenicity of DNA vaccines encoding three RhCMV proteins (a truncated version of glycoprotein B lacking the transmembrane region and endodomain [gB

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TM], phosphoprotein 65-2 [pp65-2], and viral interleukin-10 [vIL-10]) was evaluated in rhesus macaques. 

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

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TM or pp65-2, vIL-10, and gB

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TM. The vaccinees developed anti-gB and anti-pp65-2 antibodies in addition to pp65-2 cellular responses after the second booster immunization, with rapid responses observed with subsequent DNA injections. Weak vIL-10 immune responses were detected in two of the four immunized animals.

Neutralizing antibodies were detected in seven monkeys, although titers were weak compared to those observed in naturally infected animals. The immunized monkeys and na?ve controls were challenged intravenously with 105 PFU of RhCMV. Anamnestic binding and neutralizing antibody responses were observed 1 week postchallenge in the vaccinees.

DNA vaccination-induced immune responses significantly decreased peak viral loads in the immunized animals compared to those in the controls.

No difference in peak viral loads was observed between the pp65-2/gB

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TM DNA- and pp65-2/vIL-10/gB

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TM-vaccinated groups. Antibody responses to nonvaccine antigens were lower postchallenge in both vaccine groups than in the controls, suggesting long-term control of RhCMV protein expression.

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

Immunogenicity and Protective Efficacy of DNA Vaccines Expressing Rhesus Cytomegalovi

Snowy Owl

Retired in 2010, In Memoriam