Novel recombinant Mycobacterium bovis BCG, ovine atadenovirus, and modified vaccinia virus Ankara vaccines combine to induce robust human immunodeficiency virus-specific CD4 and CD8 T-cell responses in rhesus macaques

Maximillian Rosario, Richard Hopkins, John Fulkerson, Nicola Borthwick, Máire F. Quigley, Joan Joseph, Daniel C. Douek, Hui Yee Greenaway, Vanessa Venturi, Emma Gostick, David A. Price, Gerald W. Both, Jerald C. Sadoff, Tomáš Hanke

Research output: Contribution to journalArticle

Abstract

Mycobacterium bovis bacillus Calmette-Guérin (BCG), which elicits a degree of protective immunity against tuberculosis, is the most widely used vaccine in the world. Due to its persistence and immunogenicity, BCG has been proposed as a vector for vaccines against other infections, including HIV-1. BCG has a very good safety record, although it can cause disseminated disease in immunocompromised individuals. Here, we constructed a recombinant BCG vector expressing HIV-1 clade A-derived immunogen HIVA using the recently described safer and more immunogenic BCG strain AERAS-401 as the parental mycobacterium. Using routine ex vivo T-cell assays, BCG.HIVA401 as a stand-alone vaccine induced undetectable and weak CD8 T-cell responses in BALB/c mice and rhesus macaques, respectively. However, when BCG.HIVA401 was used as a priming component in heterologous vaccination regimens together with recombinant modified vaccinia virus Ankaravectored MVA.HIVA and ovine atadenovirus-vectored OAdV.HIVA vaccines, robust HIV-1-specific T-cell responses were elicited. These high-frequency T-cell responses were broadly directed and capable of proliferation in response to recall antigen. Furthermore, multiple antigen-specific T-cell clonotypes were efficiently recruited into the memory pool. These desirable features are thought to be associated with good control of HIV-1 infection. In addition, strong and persistent T-cell responses specific for the BCG-derived purified protein derivative (PPD) antigen were induced. This work is the first demonstration of immunogenicity for two novel vaccine vectors and the corresponding candidate HIV-1 vaccines BCG.HIVA401 and OAdV.HIVA in nonhuman primates. These results strongly support their further exploration.

Original languageEnglish (US)
Pages (from-to)5898-5908
Number of pages11
JournalJournal of virology
Volume84
Issue number12
DOIs
StatePublished - Jun 2010

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Rosario, M., Hopkins, R., Fulkerson, J., Borthwick, N., Quigley, M. F., Joseph, J., Douek, D. C., Greenaway, H. Y., Venturi, V., Gostick, E., Price, D. A., Both, G. W., Sadoff, J. C., & Hanke, T. (2010). Novel recombinant Mycobacterium bovis BCG, ovine atadenovirus, and modified vaccinia virus Ankara vaccines combine to induce robust human immunodeficiency virus-specific CD4 and CD8 T-cell responses in rhesus macaques. Journal of virology, 84(12), 5898-5908. https://doi.org/10.1128/JVI.02607-09