Inhibition of HIV-1 infection by monoclonal antibodies to carbohydrates of Schistosoma mansoni.
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.
Mello
Marco Antônio Gomes
MA
Laboratório Avançado de Saúde Pública, Centro de Pesquisas Gonçalo Moniz/Fiocruz, Salvador, BA, Brazil.
Mascarenhas
Rita Elizabeth
RE
Ferraro
Geraldo Argolo
GA
Harn
Donald
D
Galvão-Castro
Marco
M
Bou-Habib
Dumith Chequer
DC
D000818:Animals; D000909:Antibodies, Helminth / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000947:Antigens, Helminth / Q000276:immunology; D002241:Carbohydrates / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D009500:Neutralization Tests; D012550:Schistosoma mansoni / Q000276:immunology*
D000909:Antibodies, Helminth; D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D002241:Carbohydrates