HIV-1 neutralization: mechanisms and relevance to vaccine design.
Antibody (Ab) mediated neutralization is a crucial means of host resistance to many pathogens and will most likely be required in the development of a vaccine to protect against HIV-1. Here we examine mechanistic aspects of HIV-1 neutralization with attention to recent studies on the stoichiometric, kinetic and thermodynamic parameters involved. Neutralization of HIV-1, as with any microbe, minimally requires an initial molecular encounter with Ab. Ab occupancy of functional heterotrimers of the envelope glycoproteins, gp120 and gp41 (Env), indeed appears to be the dominant mechanism of neutralization for HIV-1. However, the Ab-binding site, the parameters mentioned above, as well as the stages and duration of vulnerability to Ab recognition, prior to and leading up to viral entry, each have a distinct impact on the mechanism of neutralization for any given Ab specificity. With HIV-1, the problems of mutational variation and neutralization resistance, coupled with the lability and conformational heterogeneity in Env, have stimulated the search for rational approaches to Env immunogen design that are unprecedented in vaccinology.
Zwick
Michael B
MB
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA. zwick@scripps.edu
Burton
Dennis R
DR
D016915:AIDS Vaccines / Q000276:immunology*; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D015704:CD4 Antigens / Q000737:chemistry / Q000276:immunology; D015195:Drug Design; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology
D016915:AIDS Vaccines; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D014614:Vaccines, Synthetic; C514787:gp41 protein, Human immunodeficiency virus 1