Recombinant Mycobacterium bovis BCG prime-recombinant adenovirus boost vaccination in rhesus monkeys elicits robust polyfunctional simian immunodeficiency virus-specific T-cell responses

Mark J. Cayabyab, Birgit Korioth-Schmitz, Yue Sun, Angela Carville, Harikrishnan Balachandran, Ayako Miura, Kevin R. Carlson, Adam P. Buzby, Barton F. Haynes, William R. Jacobs, Norman L. Letvin

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

While mycobacteria have been proposed as vaccine vectors because of their persistence and safety, little has been done systematically to optimize their immunogenicity in nonhuman primates. We successfully generated recombinant Mycobacterium bovis BCG (rBCG) expressing simian immunodeficiency virus (SIV) Gag and Pol as multigenic, nonintegrating vectors, but rBCG-expressing SIV Env was unstable. A dose and route determination study in rhesus monkeys revealed that intramuscular administration of rBCG was associated with local reactogenicity, whereas intravenous and intradermal administration of 10 6 to 108 CFU of rBCG was well tolerated. After single or repeat rBCG inoculations, monkeys developed high-frequency gamma interferon enzyme-linked immunospot responses against BCG purified protein derivative. However, the same animals developed only modest SIV-specific CD8+ T-cell responses. Nevertheless, high-frequency SIV-specific cellular responses were observed in the rBCG-primed monkeys after boosting with recombinant adenovirus 5 (rAd5) expressing the SIV antigens. These cellular responses were of greater magnitude and more persistent than those generated after vaccination with rAd5 alone. The vaccine-elicited cellular responses were predominantly polyfunctional CD8+ T cells. These findings support the further exploration of mycobacteria as priming vaccine vectors.

Original languageEnglish (US)
Pages (from-to)5505-5513
Number of pages9
JournalJournal of virology
Volume83
Issue number11
DOIs
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Cayabyab, M. J., Korioth-Schmitz, B., Sun, Y., Carville, A., Balachandran, H., Miura, A., Carlson, K. R., Buzby, A. P., Haynes, B. F., Jacobs, W. R., & Letvin, N. L. (2009). Recombinant Mycobacterium bovis BCG prime-recombinant adenovirus boost vaccination in rhesus monkeys elicits robust polyfunctional simian immunodeficiency virus-specific T-cell responses. Journal of virology, 83(11), 5505-5513. https://doi.org/10.1128/JVI.02544-08