title: HIV-1 autologous antibody neutralization associates with mother to child transmission.
abstract: The HIV-1 characteristics associated with mother to child transmission (MTCT) are still poorly understood and if known would indicate where intervention strategies should be targeted. In contrast to horizontally infected individuals, exposed infants possess inherited antibodies (Abs) from their mother with the potential to protect against infection. We investigated the HIV-1 gp160 envelope proteins from seven transmitting mothers (TM) whose children were infected either during gestation or soon after delivery and from four non-transmitting mothers (NTM) with similar viral loads and CD4 counts. Using pseudo-typed viruses we tested gp160 envelope glycoproteins for TZM-bl infectivity, CD4 and CCR5 interactions, DC-SIGN capture and transfer and neutralization with an array of common neutralizing Abs (NAbs) (2F5, 2G12, 4E10 and b12) as well as mother and infant plasma. We found no viral correlates associated with HIV-1 MTCT nor did we find differences in neutralization with the panel of NAbs. We did, however, find that TM possessed significantly higher plasma neutralization capacities than NTM (P = 0.002). Furthermore, we found that in utero (IU) TM had a higher neutralization capacity than mothers transmitting either peri - partum (PP) or via breastfeeding (BF) (P = 0.002). Plasma from children infected IU neutralized viruses carrying autologous gp160 viral envelopes as well as those from their corresponding mothers whilst plasma from children infected PP and/or BF demonstrated poor neutralizing capacity. Our results demonstrate heightened autologous NAb responses against gp120/gp41 can associate with a greater risk of HIV-1 MTCT and more specifically in those infants infected IU. Although the number of HIV-1 transmitting pairs is low our results indicate that autologous NAb responses in mothers and infants do not protect against MTCT and may in fact be detrimental when considering IU HIV-1 transmissions.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Centre for Infection and Immunity Amsterdam (CINIMA), Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Elly
authors.initials: E
authors.lastname: Baan
authors.forename: Anthony
authors.initials: A
authors.lastname: de Ronde
authors.forename: Martijn
authors.initials: M
authors.lastname: Stax
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
authors.forename: Stanley
authors.initials: S
authors.lastname: Luchters
authors.forename: Joseph
authors.initials: J
authors.lastname: Vyankandondera
authors.forename: Joep M
authors.initials: JM
authors.lastname: Lange
authors.forename: Georgios
authors.initials: G
authors.lastname: Pollakis
authors.forename: William A
authors.initials: WA
authors.lastname: Paxton
mesh_terms: D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D009500:Neutralization Tests; D010802:Phylogeny; D011247:Pregnancy
chemical_list: D015483:HIV Antibodies