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.
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.
Someya
Kenji
K
AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan. someyan@nih.go.jp
Cecilia
Dayaraj
D
Ami
Yasushi
Y
Nakasone
Tadashi
T
Matsuo
Kazuhiro
K
Burda
Sherri
S
Yamamoto
Hiroshi
H
Yoshino
Naoto
N
Kaizu
Masahiko
M
Ando
Shuji
S
Okuda
Kenji
K
Zolla-Pazner
Susan
S
Yamazaki
Shudo
S
Yamamoto
Naoki
N
Honda
Mitsuo
M
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D009163:Mycobacterium bovis / Q000235:genetics*; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011995:Recombination, Genetic; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments