title: The breadth and potency of passively acquired human immunodeficiency virus type 1-specific neutralizing antibodies do not correlate with the risk of infant infection.
abstract: Although a major goal of human immunodeficiency virus type 1 (HIV-1) vaccine efforts is to elicit broad and potent neutralizing antibodies (NAbs), there are no data that directly demonstrate a role for such NAbs in protection from HIV-1 infection in exposed humans. The setting of mother-to-child transmission provides an opportunity to examine whether NAbs provide protection from HIV-1 infection because infants acquire passive antibodies from their mothers prior to exposure to HIV-1 through breastfeeding. We evaluated the characteristics of HIV-1-specific NAbs in 100 breast-fed infants of HIV-1-positive mothers who were HIV-1 negative at birth and monitored them until age 2. A panel of eight viruses that included variants representative of those in the study region as well as more diverse strains was used to determine the breadth of the infant NAbs. From their mothers, infants acquired broad and potent NAbs that were capable of recognizing heterologous circulating HIV-1 variants of diverse subtypes, but the presence of NAbs of broad HIV-1 specificity was not associated with transmission risk. There was also no correlation between responses to any particular virus tested, which included a range of diverse variants that demonstrated different neutralization profiles, including recognition by specific antibodies with known epitope targets. The eight viruses tested exhibited neutralization profiles to a variety of monoclonal antibodies (2F5, PG9, and VRC01) similar to those of viruses present in pregnant women in the cohort. These results suggest that the breadth and potency of the heterologous antibody response in exposed infants, measured against a virus panel comprised of variants typical of those circulating in the population, does not predict protection.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Lynch
authors.forename: Ruth
authors.initials: R
authors.lastname: Nduati
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Blish
authors.forename: Barbra A
authors.initials: BA
authors.lastname: Richardson
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Mabuka
authors.forename: Zahra
authors.initials: Z
authors.lastname: Jalalian-Lechak
authors.forename: Grace
authors.initials: G
authors.lastname: John-Stewart
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D005500:Follow-Up Studies; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D018570:Risk Assessment
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies