Inhibition of HIV-1 infection by monoclonal antibodies to carbohydrates of Schistosoma mansoni |
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Authors: | Marco Antônio Gomes Mello Rita Elizabeth Mascarenhas Geraldo Argolo Ferraro Donald Harn Bernardo Galvão-Castro Dumith Chequer Bou-Habib |
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Institution: | (1) Laboratório Avançado de Saúde Pública, Centro de Pesquisas Gonçalo Moniz/Fiocruz, Salvador, BA, Brazil;(2) Escola Bahiana de Medicina e Saúde Pública, Fundação para o Desenvolvimento das Ciências, Salvador, BA, Brazil;(3) Harvard School of Public Health, Boston, Massachusetts, USA;(4) Departamento de Imunologia, Instituto Oswaldo Cruz/Fiocruz, Av. Brasil, 4365-Manguinhos, Pavilhão Leonidas Deane/409, 21045.900 Rio de Janeiro, RJ, Brazil |
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Abstract: | Patients infected with HIV-1 develop a potent humoral immune response against the virus, but HIV-1 primary isolates are remarkably resistant to neutralizing antibodies. Considering that the envelope glycoprotein of HIV-1 (gp120/41) is heavily glycosylated, we investigated whether anti-carbohydrate antibodies could inhibit HIV-1 infection in vitro. We studied the neutralizing activity of three monoclonal antibodies (mAbs) raised to carbohydrates of Schistosoma mansoni, against seven primary isolates of HIV-1. Assays were performed infecting peripheral blood mononuclear cells from normal donors with viral isolates previously treated with mAbs. Viral strains used were tropic for the coreceptors CCR5, CXCR4, and dual-tropic ones. We found that the anti-glycan mAbs vigorously inhibited HIV-1 infection, regardless of the preferential coreceptor usage of the isolate, in a dose-response manner. Importantly, five isolates were resistant to neutralization by two HIV-1 antibody-positive human sera endowed with potent anti-HIV-1 inhibitory activity. Our findings suggest that carbohydrates of the HIV-1 viral envelope may be a target of an effective humoral immune response elicited by vaccination.The first two authors contributed equally to this work |
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Keywords: | HIV-1 AIDS Neutralizing antibodies Schistosoma mansoni |
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