title: HIV-1 maternal and infant variants show similar sensitivity to broadly neutralizing antibodies, but sensitivity varies by subtype.
abstract: BACKGROUND
  To protect against HIV infection, passively transferred and/or vaccine-elicited neutralizing antibodies (NAbs) need to effectively target diverse subtypes that are transmitted globally. These variants are a limited subset of those present during chronic infection and display some unique features. In the case of mother-to-child transmission (MTCT), transmitted variants tend to be resistant to neutralization by maternal autologous NAbs.
  
  
  METHODS
  To investigate whether variants transmitted during MTCT are generally resistant to HIV-1-specific NAbs, 107 maternal or infant variants representing the dominant HIV-1 subtypes were tested against six recently identified HIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs), NIH45-46W, VRC01, PGT128, PGT121, PG9 and PGT145.
  
  
  RESULTS
  Infant and maternal variants did not differ in their neutralization sensitivity to individual bNAbs, nor did viruses from transmitting versus nontransmitting mothers, although there was a trend for viruses from transmitting mothers to be less sensitive overall. No single bNAb neutralized all viruses, but a combination of bNAbs that target distinct epitopes covered 100% of the variants tested. Compared with heterosexually transmitted variants, vertically transmitted variants were significantly more sensitive to neutralization by PGT128 and PGT121 (P=0.03 in both cases), but there were no differences for the other bNAbs. Overall, subtype A variants were significantly more sensitive to NIH45-46 (P=0.04), VRC01 (P=0.002) and PGT145 (P=0.03) compared with the nonsubtype A and less sensitive to PGT121 than subtype Cs (P=0.0001).
  
  
  CONCLUSIONS
  A combination of bNAbs against distinct epitopes may be needed to provide maximum coverage against viruses in different modes of transmission and diverse subtypes.
authors.affiliation: Division of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mabuka
authors.forename: Leslie
authors.initials: L
authors.lastname: Goo
authors.forename: Maxwel M
authors.initials: MM
authors.lastname: Omenda
authors.forename: Ruth
authors.initials: R
authors.lastname: Nduati
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D009500:Neutralization Tests
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies