Identifying epitopes of HIV-1 that induce protective antibodies
Top Cited Papers
- 1 March 2004
- journal article
- review article
- Published by Springer Nature in Nature Reviews Immunology
- Vol. 4 (3) , 199-210
- https://doi.org/10.1038/nri1307
Abstract
As with most pathogens, HIV-1 induces a polyclonal antibody response to a wide array of epitopes on different viral proteins. Studies of polyclonal sera have helped to identify several epitopes on HIV-1 envelope glycoproteins that induce protective antibodies.Antibodies to several constant regions of the virus envelope induce neutralizing antibodies, but because of the poor immunogenicity of some of these epitopes, the rare structure of neutralizing antibodies to these epitopes, or the preponderance of antibodies to particular epitopes that are non-neutralizing rather than neutralizing, targeting each of these epitopes with vaccine constructs presents difficult challenges.Antibodies to variable regions of gp120, such as V1, V2 and V3, have long been considered irrelevant to vaccine design. However, there are conserved features in the stem of the V1/V2 loop and in the V3 loop that have crucial functions in virus infectivity and explain how antibodies to these regions can be crossreactive. These conserved elements within the variable regions might therefore be relevant targets for vaccines.HIV-1 strains exist that are not neutralized by monoclonal antibodies but are neutralized by pooled sera from HIV-1+ individuals. This indicates that there might be neutralizing epitopes that have not yet been identified.Present vaccine protocols induce antibodies to many epitopes rather than focusing the immune response on epitopes that will induce protective antibodies. Given that several neutralizing epitopes in gp120 and gp41 have been identified, it might be advantageous to direct the antibody response to these protective epitopes.It is highly unlikely that a single construct will protect against all subtypes of HIV-1. Given the continuing evolution of the virus and the spread of subtypes throughout the world, the question is how to choose which strains, and how many, need to be represented in a vaccine to give maximum protection.Keywords
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