title: Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection.
abstract: Although maternal human immunodeficiency virus type 1 (HIV-1) transmission occurs during gestation, intrapartum and postpartum (by breast-feeding), 50-70% of all infected children seem to acquire HIV-1 shortly before or during delivery. Epidemiological evidence indicates that mucosal exposure is an important aspect of intrapartum HIV transmission. A simian immunodeficiency virus (SIV) macaque model has been developed that mimics the mucosal exposure that can occur during intrapartum HIV-1 transmission. To develop immunoprophylaxis against intrapartum HIV-1 transmission, we used SHIV-vpu+ (refs. 5,6), a chimeric simian-human virus that encodes the env gene of HIV-IIIB. Several combinations of human monoclonal antibodies against HIV-1 have been identified that neutralize SHIV-vpu+ completely in vitro through synergistic interaction. Here, we treated four pregnant macaques with a triple combination of the human IgG1 monoclonal antibodies F105, 2G12 and 2F5. All four macaques were protected against intravenous SHIV-vpu+ challenge after delivery. The infants received monoclonal antibodies after birth and were challenged orally with SHIV-vpu+ shortly thereafter. We found no evidence of infection in any infant during 6 months of follow-up. This demonstrates that IgG1 monoclonal antibodies protect against mucosal lentivirus challenge in neonates. We conclude that epitopes recognized by the three monoclonal antibodies are important determinants for achieving substantial protection, thus providing a rational basis for AIDS vaccine development.
authors.affiliation: Department of Cancer Immonology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Baba
authors.forename: V
authors.initials: V
authors.lastname: Liska
authors.forename: R
authors.initials: R
authors.lastname: Hofmann-Lehmann
authors.forename: J
authors.initials: J
authors.lastname: Vlasak
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: S
authors.initials: S
authors.lastname: Ayehunie
authors.forename: L A
authors.initials: LA
authors.lastname: Cavacini
authors.forename: M R
authors.initials: MR
authors.lastname: Posner
authors.forename: H
authors.initials: H
authors.lastname: Katinger
authors.forename: G
authors.initials: G
authors.lastname: Stiegler
authors.forename: B J
authors.initials: BJ
authors.lastname: Bernacky
authors.forename: T A
authors.initials: TA
authors.lastname: Rizvi
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
authors.forename: L R
authors.initials: LR
authors.lastname: Hill
authors.forename: M E
authors.initials: ME
authors.lastname: Keeling
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: J E
authors.initials: JE
authors.lastname: Wright
authors.forename: T C
authors.initials: TC
authors.lastname: Chou
authors.forename: R M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002678:Chimera; D005260:Female; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000276:immunology*; D018445:Infectious Disease Transmission, Vertical; D008253:Macaca mulatta; D009500:Neutralization Tests; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G