Recombinant Mycobacterium bovis bacillus calmette-guérin vectors prime for strong cellular responses to simian immunodeficiency virus gag in rhesus macaques

Jaimie D. Sixsmith, Michael W. Panas, Sunhee Lee, Geoffrey O. Gillard, Keri Ann White, Michelle A. Lifton, Harikrishnan Balachandran, Linh Mach, John P. Miller, Christy Lavine, C. Todd De Marco, Georgia D. Tomaras, Connie Gee, Steven A. Porcelli, Michelle H. Larsen, Richard Frothingham, Joern E. Schmitz, William R. Jacobs, Barton F. Haynes, Norman L. LetvinBirgit Korioth-Schmitz

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Live attenuated nonpathogenic Mycobacterium bovis bacillus Calmette-Guérin (BCG) mediates long-lasting immune responses, has been safely administered as a tuberculosis vaccine to billions of humans, and is affordable to produce as a vaccine vector. These characteristics make it very attractive as a human immunodeficiency virus (HIV) vaccine vector candidate. Here, we assessed the immunogenicity of recombinant BCG (rBCG) constructs with different simian immunodeficiency virus (SIV)gag expression cassettes as priming agents followed by a recombinant replication-incompetent New York vaccinia virus (NYVAC) boost in rhesus macaques. Unmutated rBCG constructs were used in comparison to mutants with gene deletions identified in an in vitro screen for augmented immunogenicity. We demonstrated that BCG-SIVgag is able to elicit robust transgene-specific priming responses, resulting in strong SIV epitope-specific cellular immune responses. While enhanced immunogenicity was sustained at moderate levels for>1 year following the heterologous boost vaccination, we were unable to demonstrate a protective effect after repeated rectal mucosal challenges with pathogenic SIVmac251. Our findings highlight the potential for rBCG vaccines to stimulate effective cross-priming and enhanced major histocompatibility complex class I presentation, suggesting that combining this approach with other immunogens may contribute to the development of effective vaccine regimens against HIV. Copyright

Original languageEnglish (US)
Pages (from-to)1385-1395
Number of pages11
JournalClinical and Vaccine Immunology
Volume21
Issue number10
DOIs
StatePublished - Oct 1 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

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    Sixsmith, J. D., Panas, M. W., Lee, S., Gillard, G. O., White, K. A., Lifton, M. A., Balachandran, H., Mach, L., Miller, J. P., Lavine, C., De Marco, C. T., Tomaras, G. D., Gee, C., Porcelli, S. A., Larsen, M. H., Frothingham, R., Schmitz, J. E., Jacobs, W. R., Haynes, B. F., ... Korioth-Schmitz, B. (2014). Recombinant Mycobacterium bovis bacillus calmette-guérin vectors prime for strong cellular responses to simian immunodeficiency virus gag in rhesus macaques. Clinical and Vaccine Immunology, 21(10), 1385-1395. https://doi.org/10.1128/CVI.00324-14