Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies

Neonatal macaques were completely protected against oral challenge with SHI V-vpu(+), a simian-human immunodeficiency virus that encodes the envelope g ene of a laboratory-adapted HIV strain, by pre- and post-natal treatment wi th a triple combination of human neutralizing monoclonal antibodies (mAbs). The mAbs were directed either against the CD4 binding site, a glycosylatio n-dependent gp120 epitope, or against a linear epitope on gp41. This triple combination was highly synergistic in vitro and neutralized primary HIV co mpletely. Subsequently, oral challenge was performed with pathogenic SHIV89 .6P, an animal-passaged variant of a chimeric virus that encodes the envelo pe gene of the primary, dual-tropic HIV89.6. Only post-natal treatment with a similar triple mAb combination was used. One out of 4 mAb-treated infant s was completely protected from infection. In the other 3 treated animals, there was a tendency towards lower peak viral RNA loads compared with untre ated controls. Two out of 4 mAb-treated infants maintained normal CD4(+) T- cell numbers, in contrast to all controls that had steep declines at 2 week s post-challenge. We conclude that the triple mAb combination significantly protected tile neonates, even against mucosal challenge with pathogenic SH IV89.6P. Passively administered synergistic human mAbs may play a role in p reventing mother-infant transmission of HIV, both against intrapartum trans mission as well as against infection through breast milk. As passive immuni zation is a tool to assess correlates of immune protection, we conclude tha t the epitopes recognized by the mAbs in our combinations are important for AIDS vaccine development. Future passive immunization studies may reveal o ther important conserved epitopes. (C) 2001 Editions scientifiques et medic ales Elsevier SAS.