Header

UZH-Logo

Maintenance Infos

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


Ruprecht, Ruth M; Hofmann-Lehmann, Regina; Smith-Franklin, B A; Rasmussen, Robert A; Liska, V; Vlasak, J; Xu, W; Baba, T W; Chenine, A L; Cavacini, L A; Posner, M R; Katinger, H; Stiegler, G; Bernacky, B J; Rizvi, T A; Schmidt, R; Hill, L R; Keeling, M E; Montefiori, D C; McClure, H M (2001). Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies. Transfusion clinique et biologique, 8(4):350-358.

Abstract

Neonatal macaques were completely protected against oral challenge with SHIV-vpu+, a simian-human immunodeficiency virus that encodes the envelope gene of a laboratory-adapted HIV strain, by pre- and post-natal treatment with a triple combination of human neutralizing monoclonal antibodies (mAbs). The mAbs were directed either against the CD4 binding site, a glycosylation-dependent gp120 epitope, or against a linear epitope on gp41. This triple combination was highly synergistic in vitro and neutralized primary HIV completely. Subsequently, oral challenge was performed with pathogenic SHIV89.6P, an animal-passaged variant of a chimeric virus that encodes the envelope 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 infants was completely protected from infection. In the other 3 treated animals, there was a tendency towards lower peak viral RNA loads compared with untreated 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 weeks post-challenge. We conclude that the triple mAb combination significantly protected the neonates, even against mucosal challenge with pathogenic SHIV89.6P. Passively administered synergistic human mAbs may play a role in preventing mother-infant transmission of HIV, both against intrapartum transmission as well as against infection through breast milk. As passive immunization is a tool to assess correlates of immune protection, we conclude that the epitopes recognized by the mAbs in our combinations are important for AIDS vaccine development. Future passive immunization studies may reveal other important conserved epitopes.

Abstract

Neonatal macaques were completely protected against oral challenge with SHIV-vpu+, a simian-human immunodeficiency virus that encodes the envelope gene of a laboratory-adapted HIV strain, by pre- and post-natal treatment with a triple combination of human neutralizing monoclonal antibodies (mAbs). The mAbs were directed either against the CD4 binding site, a glycosylation-dependent gp120 epitope, or against a linear epitope on gp41. This triple combination was highly synergistic in vitro and neutralized primary HIV completely. Subsequently, oral challenge was performed with pathogenic SHIV89.6P, an animal-passaged variant of a chimeric virus that encodes the envelope 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 infants was completely protected from infection. In the other 3 treated animals, there was a tendency towards lower peak viral RNA loads compared with untreated 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 weeks post-challenge. We conclude that the triple mAb combination significantly protected the neonates, even against mucosal challenge with pathogenic SHIV89.6P. Passively administered synergistic human mAbs may play a role in preventing mother-infant transmission of HIV, both against intrapartum transmission as well as against infection through breast milk. As passive immunization is a tool to assess correlates of immune protection, we conclude that the epitopes recognized by the mAbs in our combinations are important for AIDS vaccine development. Future passive immunization studies may reveal other important conserved epitopes.

Statistics

Citations

34 citations in Web of Science®
40 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 05 Dec 2016
0 downloads since 12 months

Additional indexing

Other titles:Protection de l’infection expérimentale SHIV chez les macaques nouveau-nés par des anticorps humains neutralisants.
Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinary Clinic > Department of Farm Animals
Dewey Decimal Classification:570 Life sciences; biology
630 Agriculture
Uncontrolled Keywords:neutralizing monoclonal antibodies against HIV; oral transmission; passive immunization; rhesus monkeys; simian-human immunodeficiency virus
Language:English
Date:August 2001
Deposited On:05 Dec 2016 13:04
Last Modified:05 Dec 2016 13:04
Publisher:Elsevier
ISSN:1246-7820
Publisher DOI:https://doi.org/10.1016/S1246-7820(01)00187-2
PubMed ID:11642027

Download