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1.
Transfus Clin Biol ; 8(4): 350-8, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11642027

RESUMO

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.


Assuntos
Vacinas contra a AIDS/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Anticorpos Anti-HIV/administração & dosagem , Infecções por HIV/prevenção & controle , HIV/imunologia , Imunização Passiva , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/imunologia , Vacinação , Vacinas contra a AIDS/imunologia , Administração Oral , Animais , Animais Recém-Nascidos , Anticorpos Monoclonais/imunologia , Contagem de Linfócito CD4 , Cesárea , Parto Obstétrico , Modelos Animais de Doenças , Feminino , Anticorpos Anti-HIV/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp41 do Envelope de HIV/imunologia , Humanos , Imunidade Materno-Adquirida , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Lactação , Macaca mulatta , Troca Materno-Fetal , Leite/virologia , Testes de Neutralização , Projetos Piloto , Gravidez , Complicações Infecciosas na Gravidez/virologia , Especificidade da Espécie , Montagem de Vírus , Eliminação de Partículas Virais
2.
J Hum Virol ; 4(2): 55-61, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11437315

RESUMO

OBJECTIVES: We investigated the ability of several human neutralizing monoclonal antibodies (mAbs), originally raised against human immunodeficiency virus (HIV) clade B isolates, to neutralize primary clade C isolates as single agents and in combination. STUDY DESIGN/METHODS: HIV clade C isolates from five different countries were tested for susceptibility to neutralization by anti-clade B mAbs in human peripheral blood mononuclear cells. Monoclonal antibody combinations were evaluated for possible synergy. RESULTS: All 20 primary HIV clade C isolates could be neutralized 97.5% to 100% by a quadruple combination of mAbs IgG1b12, 2G12, 2F5, and 4E10. These mAbs recognized conserved epitopes and were highly synergistic, resulting in strong cross-clade neutralization. CONCLUSIONS: In our previous experiment, a synergistic combination of human neutralizing mAbs protected all macaque neonates against oral challenge with a simian-human immunodeficiency virus encoding HIV env. Together, our data suggest that passive immunization with currently available anti-clade B mAbs could play a role in preventing HIV clade C transmission through breastfeeding.


Assuntos
Anticorpos Monoclonais/imunologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/imunologia , Especificidade de Anticorpos , Reações Antígeno-Anticorpo , Sinergismo Farmacológico , Anticorpos Anti-HIV/imunologia , Humanos , Leucócitos Mononucleares/virologia , Testes de Neutralização
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