Postnatal passive immunization of neonatal macaques with a triple combination of human monoclonal antibodies against oral simian-human immunodeficiency virus challenge

To develop prophylaxis against mother-to-child human immunodeficiency virus (HM transmission, we established a simian-human immunodeficiency virus (SH IV) infection model in neonatal macaques that mimics intrapartum mucosal vi rus exposure (T. W. Baba et al., AIDS Res. Hum. Retroviruses 10:351-357, 19 94). Using this model, neonates were protected from mucosal SHIV-vpu(+) cha llenge by pre- and postnatal treatment with a combination of three human ne utralizing monoclonal antibodies (MAbs), F105, 2G12, and 2F5 (Baba et al., Nat. Med. 6:200-206, 2000). In the present study, we used this MAb combinat ion only postnatally, thereby significantly reducing the quantity of antibo dies necessary and rendering their potential use in humans more practical. We protected two neonates with this regimen against oral SHIV-vpu(+) challe nge, while four untreated control animals became persistently infected. Thu s, synergistic MAbs protect when used as immunoprophylaxis without the pren atal 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 a lone does not neutralize SHIV89.6P. We administered the combination of MAbs IgG1b12, 2F5, and 2G12 postnatally to four neonates. One of the four infan ts remained uninfected after oral challenge with SHIV89.6P, and two infants had no or a delayed CD4(+) T-cell decline. In contrast, all control animal s had dramatic drops in their CD4(+) T cells by 2 weeks postexposure. We co nclude that our triple MAb combination partially protected against mucosal challenge with the highly pathogenic SHIV89.6P. Thus, combination immunopro phylaxis with passively administered synergistic human MAbs may play a role in the clinical prevention of mother-to-infant transmission of HIV type 1.