Multi-envelope HIV-1 vaccine devoid of SIV components controls disease in macaques challenged with heterologous pathogenic SHIV.
A central obstacle to the design of a global HIV-1 vaccine is virus diversity. Pathogen diversity is not unique to HIV-1, and has been successfully conquered in other fields by the creation of vaccine cocktails. Here we describe the testing of an HIV-1 envelope cocktail vaccine. Six macaques received the vaccine, delivered by successive immunizations with recombinant DNA, recombinant vaccinia virus and recombinant envelope proteins. Following vaccination, animals developed a diversity of anti-envelope antibody binding and neutralizing activities toward proteins and viruses that were not represented by sequence in the vaccine. T-cells were also elicited, as measured by gamma-interferon production assays with envelope-derived peptide pools. Vaccinated and control animals were then challenged with the heterologous pathogenic SHIV, 89.6P. Vaccinated monkeys experienced significantly lower virus titers and better maintenance of CD4+ T-cells than unvaccinated controls. The B- and T-cell immune responses were far superior post-challenge in the vaccinated group. Four of six vaccinated animals and only one of six control animals survived a 44-week observation period post-challenge. The present report is the first to describe pathogenic SHIV disease control mediated by a heterologous HIV-1 vaccine, devoid of 89.6 or SIV derivatives.
Zhan
Xiaoyan
X
Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
Martin
Louis N
LN
Slobod
Karen S
KS
Coleclough
Chris
C
Lockey
Timothy D
TD
Brown
Scott A
SA
Stambas
John
J
Bonsignori
Mattia
M
Sealy
Robert E
RE
Blanchard
James L
JL
Hurwitz
Julia L
JL
D016915:AIDS Vaccines / Q000627:therapeutic use*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D018791:CD4 Lymphocyte Count; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects*; D008253:Macaca mulatta; D009500:Neutralization Tests; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014611:Vaccination; D019562:Viral Load
D016915:AIDS Vaccines