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Titolo:
Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies
Autore:
Ruprecht, RM; Hofmann-Lehmann, R; Smith-Franklin, BA; Rasmussen, RA; Liska, V; Vlasak, J; Xu, W; Baba, TW; Chenine, AL; Cavacini, LA; Posner, MR; Katinger, H; Stiegler, G; Bernacky, BJ; Rizvi, TA; Schmidt, R; Hill, LR; Keeling, ME; Montefiori, DC; McClure, HM;
Indirizzi:
Dana Farber Canc Inst, Boston, MA 02115 USA Dana Farber Canc Inst Boston MA USA 02115 Canc Inst, Boston, MA 02115 USA Harvard Univ, Sch Med, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 vard Univ, Sch Med, Boston, MA 02115 USA Tufts Univ, Sch Med, Div Newborn Med, Dept Pediat, Boston, MA 02111 USA Tufts Univ Boston MA USA 02111 orn Med, Dept Pediat, Boston, MA 02111 USA Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA Beth Israel Deaconess Med Ctr Boston MA USA 02215 r, Boston, MA 02215 USA Inst Appl Microbiol, A-1190 Vienna, Austria Inst Appl Microbiol Vienna Austria A-1190 robiol, A-1190 Vienna, Austria Univ Texas, MD Anderson Canc Ctr, Dept Vet Sci, Bastrop, TX 78602 USA UnivTexas Bastrop TX USA 78602 Ctr, Dept Vet Sci, Bastrop, TX 78602 USA Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA Duke Univ Durham NC USA 27710 v, Med Ctr, Dept Surg, Durham, NC 27710 USA Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30329 USA Emory Univ Atlanta GA USA 30329 eg Primate Res Ctr, Atlanta, GA 30329 USA
Titolo Testata:
TRANSFUSION CLINIQUE ET BIOLOGIQUE
fascicolo: 4, volume: 8, anno: 2001,
pagine: 350 - 358
SICI:
1246-7820(200108)8:4<350:PONMAE>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; COMPLEMENT-MEDIATED LYSIS; SYNERGISTIC NEUTRALIZATION; RHESUS-MONKEYS; IN-VIVO; ENVELOPE GLYCOPROTEIN; HIV-1 INFECTION; TYPE-1; COMBINATIONS; TRANSMISSION;
Keywords:
neutralizing monoclonal antibodies against HIV oral transmission; passive immunization; rhesus monkeys; simian-human immunodeficiency virus;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Ruprecht, RM Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA Dana Farber Canc Inst 44 Binney St Boston MA USA 02115 15 USA
Citazione:
R.M. 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

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 tile 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. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

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Documento generato il 04/04/20 alle ore 15:18:51