Vaccine-induced control of viral shedding following rhesus cytomegalovirus challenge in rhesus macaques

Kristina Abel, Joy Martinez, Yujuan Yue, Simon F. Lacey, Zhongde Wang, Lisa Strelow, Anindya Dasgupta, Zhongqi Li, Kimberli A. Schmidt, Kristie L. Oxford, Basel Assaf, Jeffrey A. Longmate, Don J. Diamond, Peter A. Barry

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33 Scopus citations

Abstract

The use of animal models of human cytomegalovirus (HCMV) infection is critical to refine HCMV vaccine candidates. Previous reports have demonstrated that immunization of rhesus monkeys against rhesus cytomegalovirus (RhCMV) can reduce both local and systemic replication of RhCMV following experimental RhCMV challenge. These studies used prime/boost combinations of DNA expression plasmids alone or DNA priming and boosting with either inactivated virion particles or modified vaccinia virus Ankara (MVA) expressing the same antigens. Viral outcomes included reduced RhCMV replication at the site of subcutaneous inoculation and RhCMV viremia following intravenous inoculation. Since shedding of cytomegalovirus from mucosal surfaces is critical for horizontal transmission of the virus, DNA priming/MVA boosting was evaluated for the ability to reduce oral shedding of RhCMV following subcutaneous challenge. Of six rhesus monkeys vaccinated exclusively against RhCMV glycoprotein B (gB), phosphoprotein 65 (pp65), and immediate-early 1 (IE1), half showed viral loads in saliva that were lower than those of control monkeys by 1 to 3 orders of magnitude. Further, there was a strong association of memory pp65 T cell responses postchallenge in animals exhibiting the greatest reduction in oral shedding. These results highlight the fact that a DNA/MVA vaccination regimen can achieve a notable reduction in a critical parameter of viral replication postchallenge. The recently completed clinical trial of a gB subunit vaccine in which the rate of HCMV infection was reduced by 50% in the individuals receiving the vaccine is consistent with the results of this study suggesting that additional immunogens are likely essential for maximum protection in an outbred human population.

Original languageEnglish (US)
Pages (from-to)2878-2890
Number of pages13
JournalJournal of Virology
Volume85
Issue number6
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Abel, K., Martinez, J., Yue, Y., Lacey, S. F., Wang, Z., Strelow, L., ... Barry, P. A. (2011). Vaccine-induced control of viral shedding following rhesus cytomegalovirus challenge in rhesus macaques. Journal of Virology, 85(6), 2878-2890. https://doi.org/10.1128/JVI.00883-10