HIV This Week

Hurwitz JL, Zhan X, Brown SA, Bonsignori M, Stambas J, Lockey TD, Sealy R, Surman S, Freiden P, Jones B, Martin L, Blanchard J, Slobod KS. HIV-1 vaccine development: tackling virus diversity with a multi-envelope cocktail. Front Biosci 2008; 13:609-20.

A major obstacle to the design of a global HIV-1 vaccine is viral diversity. At present, data suggest that a vaccine comprising a single antigen will fail to generate broadly reactive B-cell and T-cell responses able to confer protection against the diverse isolates of HIV-1. While some B-cell and T-cell epitopes lie within the more conserved regions of HIV-1 proteins, many are localized to variable regions and differ from one virus to the next. Neutralizing B-cell responses may vary toward viruses with different i) antibody contact residues and/or ii) protein conformations while T-cell responses may vary toward viruses with different (i) T-cell receptor contact residues and/or (ii) amino acid sequences pertinent to antigen processing. Here Hurwitz and colleagues review previous and current strategies for HIV-1 vaccine development. The authors focus on studies at St. Jude Children’s Research Hospital dedicated to the development of an HIV-1 vaccine cocktail strategy. The St. Jude Children’s Research Hospital multi-vectored, multi-envelope vaccine has now been shown to elicit HIV-1-specific B- and T-cell functions with a diversity and durability that may be required to prevent HIV-1 infections in humans.

Editors’ note: The large number of circulating variants, with vulnerability present both within and between subtypes and within virtually all HIV-1 proteins, poses a challenge to vaccine development unique to HIV. Even the five designated ‘conserved’ regions as opposed to the ‘hypervariable’ regions are heterogeneous. Whether the positive finding of the cocktail approach of a multi-envelope vaccine in macaques challenged with artificial virus can be replicated in humans remains to be seen.