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Journal of Virology, February 2005, p. 1452-1462, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1452-1462.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Vaccination of Rhesus Macaques with Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Env V3 Elicits Neutralizing Antibody-Mediated Protection against Simian-Human Immunodeficiency Virus with a Homologous but Not a Heterologous V3 Motif

Kenji Someya,1* Dayaraj Cecilia,2 Yasushi Ami,3 Tadashi Nakasone,1 Kazuhiro Matsuo,1,4 Sherri Burda,2 Hiroshi Yamamoto,5 Naoto Yoshino,6 Masahiko Kaizu,1,4 Shuji Ando,1 Kenji Okuda,7 Susan Zolla-Pazner,2 Shudo Yamazaki,1 Naoki Yamamoto,1 and Mitsuo Honda1,4

AIDS Research Center,1 and Division of Experimental Animal Research, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo,3 Yokohama City University, Kanazawa-ku, Yokohama,7 Japan Science and Technology Corporation, Kawaguchi, Saitama,4 Toyama Medical Pharmaceutical University, Toyama, Toyama,5 Iwate Medical University, Morioka, Iwate, Japan,6 New York University Medical Center, New York, New York2

Received 25 June 2004/ Accepted 23 September 2004

Although the correlates of vaccine-induced protection against human immunodeficiency virus type 1 (HIV-1) are not fully known, it is presumed that neutralizing antibodies (NAb) play a role in controlling virus infection. In this study, we examined immune responses elicited in rhesus macaques following vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing an HIV-1 Env V3 antigen (rBCG Env V3). We also determined the effect of vaccination on protection against challenge with either a simian-human immunodeficiency virus (SHIV-MN) or a highly pathogenic SHIV strain (SHIV-89.6PD). Immunization with rBCG Env V3 elicited significant levels of NAb for the 24 weeks tested that were predominantly HIV-1 type specific. Sera from the immunized macaques neutralized primary HIV-1 isolates in vitro, including HIV-1BZ167/X4, HIV-1SF2/X4, HIV-1CI2/X4, and, to a lesser extent, HIV-1MNp/X4, all of which contain a V3 sequence homologous to that of rBCG Env V3. In contrast, neutralization was not observed against HIV-1SF33/X4, which has a heterologous V3 sequence, nor was it found against primary HIV-1 R5 isolates from either clade A or B. Furthermore, the viral load in the vaccinated macaques was significantly reduced following low-dose challenge with SHIV-MN, and early plasma viremia was markedly decreased after high-dose SHIV-MN challenge. In contrast, replication of pathogenic SHIV-89.6PD was not affected by vaccination in any of the macaques. Thus, we have shown that immunization with an rBCG Env V3 vaccine elicits a strong, type-specific V3 NAb response in rhesus macaques. While this response was not sufficient to provide protection against a pathogenic SHIV challenge, it was able to significantly reduce the viral load in macaques following challenge with a nonpathogenic SHIV. These observations suggest that rBCG vectors have the potential to deliver an appropriate virus immunogen for desirable immune elicitations.

* Corresponding author. Mailing address: AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan. Phone: 81-3-5285-1111, ext. 2737. Fax: 81-3-5285-1183. E-mail: someyan{at}nih.go.jp.

Journal of Virology, February 2005, p. 1452-1462, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1452-1462.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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