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Journal of Virology, June 2009, p. 5505-5513, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02544-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Recombinant Mycobacterium bovis BCG Prime-Recombinant Adenovirus Boost Vaccination in Rhesus Monkeys Elicits Robust Polyfunctional Simian Immunodeficiency Virus-Specific T-Cell Responses{triangledown}

Mark J. Cayabyab,1,{dagger} Birgit Korioth-Schmitz,1 Yue Sun,1 Angela Carville,2 Harikrishnan Balachandran,1 Ayako Miura,1 Kevin R. Carlson,1 Adam P. Buzby,1 Barton F. Haynes,3 William R. Jacobs,4 and Norman L. Letvin1*

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,1 New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772,2 Duke University School of Medicine, Durham, North Carolina 27710,3 Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York 104614

Received 10 December 2008/ Accepted 11 March 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 106 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.

* Corresponding author. Mailing address: Department of Medicine, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Center for Life Science, 330 Brookline Avenue, Boston, MA 02215. Phone: (617) 735-4400. Fax: (617) 735-4527. E-mail: nletvin{at}bidmc.harvard.edu

{triangledown} Published ahead of print on 18 March 2009.

{dagger} Present address: The Forsyth Institute, 140 The Fenway, Boston, MA 02115.

Journal of Virology, June 2009, p. 5505-5513, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02544-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sun, Y., Bailer, R. T., Rao, S. S., Mascola, J. R., Nabel, G. J., Koup, R. A., Letvin, N. L. (2009). Systemic and Mucosal T-Lymphocyte Activation Induced by Recombinant Adenovirus Vaccines in Rhesus Monkeys. J. Virol. 83: 10596-10604 [Abstract] [Full Text]  


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