title: Evidence for a continuous drift of the HIV-1 species towards higher resistance to neutralizing antibodies over the course of the epidemic.
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, NIH45-46(G54W), PG9, PG16, PGT121, PGT128, PGT145). Despite this evolution, a combination of two HuMoNAbs (NIH45-46(G54W) 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.
authors.affiliation: Université François Rabelais, Inserm U966, Tours, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bouvin-Pley
authors.forename: Marion
authors.initials: M
authors.lastname: Morgand
authors.forename: Alain
authors.initials: A
authors.lastname: Moreau
authors.forename: Pauline
authors.initials: P
authors.lastname: Jestin
authors.forename: Claire
authors.initials: C
authors.lastname: Simonnet
authors.forename: Laurent
authors.initials: L
authors.lastname: Tran
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.forename: Francis
authors.initials: F
authors.lastname: Barin
authors.forename: Martine
authors.initials: M
authors.lastname: Braibant
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000378:metabolism*; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D058872:Epidemics; D062665:Epidemiological Monitoring; D000939:Epitopes / Q000235:genetics; D005602:France / Q000453:epidemiology; D040961:Genetic Drift; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D056724:Immunity, Humoral; D055261:Immunogenetic Phenomena; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000956:Antigens, Viral; D000939:Epitopes; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D014759:Viral Envelope Proteins