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
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Published:2005-02
Issue:3
Volume:79
Page:1452-1462
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ISSN:0022-538X
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Container-title:Journal of Virology
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language:en
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Short-container-title:J Virol
Author:
Someya Kenji1, Cecilia Dayaraj2, Ami Yasushi3, Nakasone Tadashi1, Matsuo Kazuhiro14, Burda Sherri2, Yamamoto Hiroshi5, Yoshino Naoto6, Kaizu Masahiko14, Ando Shuji1, Okuda Kenji7, Zolla-Pazner Susan2, Yamazaki Shudo1, Yamamoto Naoki1, Honda Mitsuo14
Affiliation:
1. AIDS Research Center 2. New York University Medical Center, New York, New York 3. and Division of Experimental Animal Research, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 4. Japan Science and Technology Corporation, Kawaguchi, Saitama 5. Toyama Medical Pharmaceutical University, Toyama, Toyama 6. Iwate Medical University, Morioka, Iwate, Japan 7. Yokohama City University, Kanazawa-ku, Yokohama
Abstract
ABSTRACT
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-1
BZ167/X4
, HIV-1
SF2/X4
, HIV-1
CI2/X4
, and, to a lesser extent, HIV-1
MNp/X4
, all of which contain a V3 sequence homologous to that of rBCG Env V3. In contrast, neutralization was not observed against HIV-1
SF33/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.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
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