title: Role of maternal autologous neutralizing antibody in selective perinatal transmission of human immunodeficiency virus type 1 escape variants.
abstract: Perinatal human immunodeficiency virus type 1 (HIV-1) transmission is characterized by acquisition of a homogeneous viral quasispecies, yet the selective factors responsible for this genetic bottleneck are unclear. We examined the role of maternal autologous neutralizing antibody (aNAB) in selective transmission of HIV-1 escape variants to infants. Maternal sera from 38 infected mothers at the time of delivery were assayed for autologous neutralizing antibody activity against maternal time-of-delivery HIV-1 isolates in vitro. Maternal sera were also tested for cross-neutralization of infected-infant-first-positive-time-point viral isolates. Heteroduplex and DNA sequence analyses were then performed to identify the initial infecting virus as a neutralization-sensitive or escape HIV-1 variant. In utero transmitters (n = 14) were significantly less likely to have aNAB to their own HIV-1 strains at delivery than nontransmitting mothers (n = 17, 14.3% versus 76.5%, P = 0.003). Cross-neutralization assays of infected-infant-first-positive-time-point HIV-1 isolates indicated that while 14/21 HIV-1-infected infant first positive time point isolates were resistant to their own mother's aNAB, no infant isolate was inherently resistant to antibody neutralization by all sera tested. Furthermore, both heteroduplex (n = 21) and phylogenetic (n = 9) analyses showed that selective perinatal transmission and/or outgrowth of maternal autologous neutralization escape HIV-1 variants occurs in utero and intrapartum. These data indicate that maternal autologous neutralizing antibody can exert powerful protective and selective effects in perinatal HIV-1 transmission and therefore has important implications for vaccine development.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, University of California-Los Angeles, 10833 LeConte Ave., Los Angeles, CA 90095, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Dickover
authors.forename: Eileen
authors.initials: E
authors.lastname: Garratty
authors.forename: Karina
authors.initials: K
authors.lastname: Yusim
authors.forename: Catherine
authors.initials: C
authors.lastname: Miller
authors.forename: Bette
authors.initials: B
authors.lastname: Korber
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Bryson
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D001483:Base Sequence; D005260:Female; D006679:HIV Seropositivity / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D007743:Labor, Obstetric / Q000097:blood* / Q000235:genetics / Q000276:immunology; D008431:Maternal-Fetal Exchange; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010802:Phylogeny; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D017423:Sequence Analysis, RNA; D013045:Species Specificity
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral