title: Passive immunization against oral AIDS virus transmission: an approach to prevent mother-to-infant HIV-1 transmission?
abstract: To develop immunoprophylaxis regimens against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, we established a simian-human immunodeficiency virus (SHIV) model in neonatal macaques that mimics intrapartum mucosal virus exposure (T.W. Baba, J. Koch, E.S. Mittler et al: AIDS Res Hum Retroviruses 10:351-357, 1994). We protected four neonates from oral SHIV-vpu+ challenge by ante- and postpartum treatment with a synergistic triple combination of immunoglobulin (Ig) G1 human anti-HIV-1 neutralizing monoclonal antibodies (mAbs) (T.W. Baba, V. Liska, R. Hofmann-Lehmann et al: Nature Med 6:200-206, 2000), which recognize the CD4-binding site of Env, a glycosylation-dependent gp120, or a linear gp41 epitope. Two neonates that received only postpartum mAbs were also protected from oral SHIV-vpu+ challenge, indicating that postpartum treatment alone is sufficient. Next, we evaluated a similar mAb combination against SHIV89.6P, which encodes env of primary HIV89.6. One of four mAb-treated neonates was protected from infection and two maintained normal CD4+ T-cell counts. We conclude that the epitopes recognized by the three mAbs are important determinants for achieving protection. Combination immunoprophylaxis with synergistic mAbs seems promising to prevent maternal HIV-1 transmission in humans.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115-6084, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hofmann-Lehmann
authors.forename: R A
authors.initials: RA
authors.lastname: Rasmussen
authors.forename: J
authors.initials: J
authors.lastname: Vlasak
authors.forename: B A
authors.initials: BA
authors.lastname: Smith
authors.forename: T W
authors.initials: TW
authors.lastname: Baba
authors.forename: V
authors.initials: V
authors.lastname: Liska
authors.forename: D C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: H M
authors.initials: HM
authors.lastname: McClure
authors.forename: D C
authors.initials: DC
authors.lastname: Anderson
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: H
authors.initials: H
authors.lastname: Katinger
authors.forename: G
authors.initials: G
authors.lastname: Stiegler
authors.forename: M R
authors.initials: MR
authors.lastname: Posner
authors.forename: L A
authors.initials: LA
authors.lastname: Cavacini
authors.forename: T C
authors.initials: TC
authors.lastname: Chou
authors.forename: R M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control / Q000635:transmission*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002678:Chimera; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000627:therapeutic use; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008253:Macaca mulatta; D008297:Male; D049590:Postpartum Period; D011247:Pregnancy; D015302:Simian Immunodeficiency Virus / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G