Evidence for a Continuous Drift of the HIV-1 Species towards Higher Resistance to Neutralizing Antibodies over the Course of the Epidemic

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. © 2013 bouvin-pley et al.