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

Citation
Rm. Ruprecht et al., Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies, TRANSF CL B, 8(4), 2001, pp. 350-358
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology
Journal title
TRANSFUSION CLINIQUE ET BIOLOGIQUE
ISSN journal
1246-7820 → ACNP
Volume
8
Issue
4
Year of publication
2001
Pages
350 - 358
Database
ISI
SICI code
1246-7820(200108)8:4<350:PONMAE>2.0.ZU;2-O
Abstract
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.