title: Postnatal passive immunization of neonatal macaques with a triple combination of human monoclonal antibodies against oral simian-human immunodeficiency virus challenge.
abstract: To develop prophylaxis against mother-to-child human immunodeficiency virus (HIV) transmission, we established a simian-human immunodeficiency virus (SHIV) infection model in neonatal macaques that mimics intrapartum mucosal virus exposure (T. W. Baba et al., AIDS Res. Hum. Retroviruses 10:351-357, 1994). Using this model, neonates were protected from mucosal SHIV-vpu(+) challenge by pre- and postnatal treatment with a combination of three human neutralizing monoclonal antibodies (MAbs), F105, 2G12, and 2F5 (Baba et al., Nat. Med. 6:200-206, 2000). In the present study, we used this MAb combination only postnatally, thereby significantly reducing the quantity of antibodies necessary and rendering their potential use in humans more practical. We protected two neonates with this regimen against oral SHIV-vpu(+) challenge, while four untreated control animals became persistently infected. Thus, synergistic MAbs protect when used as immunoprophylaxis without the prenatal dose. We then determined in vitro the optimal MAb combination against the more pathogenic SHIV89.6P, a chimeric virus encoding env of the primary HIV89.6. Remarkably, the most potent combination included IgG1b12, which alone does not neutralize SHIV89.6P. We administered the combination of MAbs IgG1b12, 2F5, and 2G12 postnatally to four neonates. One of the four infants remained uninfected after oral challenge with SHIV89.6P, and two infants had no or a delayed CD4(+) T-cell decline. In contrast, all control animals had dramatic drops in their CD4(+) T cells by 2 weeks postexposure. We conclude that our triple MAb combination partially protected against mucosal challenge with the highly pathogenic SHIV89.6P. Thus, combination immunoprophylaxis with passively administered synergistic human MAbs may play a role in the clinical prevention of mother-to-infant transmission of HIV type 1.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hofmann-Lehmann
authors.forename: J
authors.initials: J
authors.lastname: Vlasak
authors.forename: R A
authors.initials: RA
authors.lastname: Rasmussen
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: F
authors.initials: F
authors.lastname: Ferrantelli
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: L A
authors.initials: LA
authors.lastname: Cavacini
authors.forename: M R
authors.initials: MR
authors.lastname: Posner
authors.forename: T C
authors.initials: TC
authors.lastname: Chou
authors.forename: J
authors.initials: J
authors.lastname: Andersen
authors.forename: R M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D004357:Drug Synergism; D006801:Humans; D018928:Immunity, Mucosal; D007116:Immunization, Passive; D008251:Macaca; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000635:transmission; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal