Abstract
We compared the neutralization sensitivity of early/transmitted HIV-1 variants from patients infected by subtype B viruses at 3 periods of the epidemic (1987–1991, 1996–2000, 2006–2010). Infectious pseudotyped viruses expressing envelope glycoproteins representative of the viral quasi-species infecting each patient were tested for sensitivity to neutralization by pools of sera from HIV-1 chronically infected patients and by an updated panel of 13 human monoclonal neutralizing antibodies (HuMoNAbs). A progressive significantly enhanced resistance to neutralization was observed over calendar time, by both human sera and most of the HuMoNAbs tested (b12, VRC01, VRC03, NIH45-46G54W, PG9, PG16, PGT121, PGT128, PGT145). Despite this evolution, a combination of two HuMoNAbs (NIH45-46G54W and PGT128) still would efficiently neutralize the most contemporary transmitted variants. In addition, we observed a significant reduction of the heterologous neutralizing activity of sera from individuals infected most recently (2003–2007) compared to patients infected earlier (1987–1991), suggesting that the increasing resistance of the HIV species to neutralization over time coincided with a decreased immunogenicity. These data provide evidence for an ongoing adaptation of the HIV-1 species to the humoral immunity of the human population, which may add an additional obstacle to the design of an efficient HIV-1 vaccine.
Highlights
Thirty years after the discovery of the human immunodeficiency virus (HIV), the development of an effective vaccine remains an elusive goal
The aim of our study was to check if, subsequently to the selective pressure exerted by the individual neutralizing antibodies (NAbs) responses, the HIV-1 species has evolved at the population level towards an enhanced resistance to antibody neutralization
By comparing HIV-1 subtype B variants collected at three periods spanning more than 2 decades, we found a significantly progressive enhanced resistance to neutralization of the HIV-1 species over time
Summary
Thirty years after the discovery of the human immunodeficiency virus (HIV), the development of an effective vaccine remains an elusive goal. It has become clear that a substantial number of HIV-1 infected individuals develop NAbs after 2 or 3 years of infection able to neutralize efficiently heterologous primary isolates of various subtypes [29,30,31,32] This means that the relevant epitope(s) exist toward which a specific response can be mounted, at least in some individuals. Several studies suggested that broad and potent neutralizing activity in most of the sera from patients with broadly NAbs arises through a limited number of specificities that correspond to the targets of these HuMoNAbs [42,43,44,45] These targets are epitopes located within the surface glycoprotein gp120. Some of them overlap the CD4 binding site [39,46,47] and others are more complex, of glycopeptidic nature, composed of conserved glycans and amino-acid residues of the V1, V2 and V3 loops [48,49]
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