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

Publication ,  Journal Article
Cayabyab, MJ; Korioth-Schmitz, B; Sun, Y; Carville, A; Balachandran, H; Miura, A; Carlson, KR; Buzby, AP; Haynes, BF; Jacobs, WR; Letvin, NL
Published in: J Virol
June 2009

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 10(8) 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.

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

June 2009

Volume

83

Issue

11

Start / End Page

5505 / 5513

Location

United States

Related Subject Headings

  • Virology
  • Vaccines, Synthetic
  • Titrimetry
  • T-Lymphocytes
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Mycobacterium bovis
  • Macaca mulatta
  • Immunization, Secondary
  • Genetic Vectors
 

Citation

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Cayabyab, M. J., Korioth-Schmitz, B., Sun, Y., Carville, A., Balachandran, H., Miura, A., … 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. J Virol, 83(11), 5505–5513. https://doi.org/10.1128/JVI.02544-08
Cayabyab, Mark J., Birgit Korioth-Schmitz, Yue Sun, Angela Carville, Harikrishnan Balachandran, Ayako Miura, Kevin R. Carlson, et al. “Recombinant Mycobacterium bovis BCG prime-recombinant adenovirus boost vaccination in rhesus monkeys elicits robust polyfunctional simian immunodeficiency virus-specific T-cell responses.J Virol 83, no. 11 (June 2009): 5505–13. https://doi.org/10.1128/JVI.02544-08.
Cayabyab MJ, Korioth-Schmitz B, Sun Y, Carville A, Balachandran H, Miura A, Carlson KR, Buzby AP, Haynes BF, Jacobs WR, Letvin NL. Recombinant Mycobacterium bovis BCG prime-recombinant adenovirus boost vaccination in rhesus monkeys elicits robust polyfunctional simian immunodeficiency virus-specific T-cell responses. J Virol. 2009 Jun;83(11):5505–5513.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

June 2009

Volume

83

Issue

11

Start / End Page

5505 / 5513

Location

United States

Related Subject Headings

  • Virology
  • Vaccines, Synthetic
  • Titrimetry
  • T-Lymphocytes
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Mycobacterium bovis
  • Macaca mulatta
  • Immunization, Secondary
  • Genetic Vectors