RESUMO
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.
Assuntos
Anticorpos Anti-Helmínticos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Carboidratos/imunologia , Infecções por HIV/tratamento farmacológico , Schistosoma mansoni/imunologia , Animais , Antígenos de Helmintos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Testes de NeutralizaçãoRESUMO
Recently, we reported a partial characterization of the epitope recognized by the ES-78 monoclonal antibody (MoAb). This monoclonal antibody was obtained from spleen lymphocytes of a mouse immunized with excretory-secretory antigens of Fasciola hepatica adult worms. In the present study, we report the results obtained in experiments of passive protection using this MoAb in BALB/c mice infected with 15 Fasciola hepatica metacercariae. The monoclonal antibody was able to reduce the parasite burden when administered 24 h before challenge but not when delivered 7 days after challenge. The antibody recognition of digestive tract structures in 3-week-old parasites was demonstrated by immune histochemical techniques. The antigens purified by affinity chromatography using this antibody had molecular weights of 14-20, 25-29 and 36-45 kDa and demonstrated proteinase activity similar to cathepsin L. These results suggest that the antigens carrying the epitope recognized by the ES-78 MoAb may be used as target in the protection against fasciolosis.
Assuntos
Anticorpos Anti-Helmínticos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Fasciola hepatica/imunologia , Fasciolíase/prevenção & controle , Imunização Passiva , Animais , Anticorpos Anti-Helmínticos/administração & dosagem , Anticorpos Anti-Helmínticos/imunologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Antígenos de Helmintos/química , Cisteína Endopeptidases/análise , Cisteína Endopeptidases/imunologia , Fasciolíase/parasitologia , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
We have been able to produce a mouse monoclonal IgE antibody specific to an adult worm antigen extracted from Schistosoma japonicum (Sj). The antibody was able to elicit passive cutaneous anaphylaxis in the rat skin against Sj with the highest titer of 1:256,000 but did not cross-react with S. mansoni antigen. The antibody recognized a 97-kDa molecule expressed on the surface of mechanically transformed schistosoma of S. japonicum. Passive transfer of the antibody into mice in the early stage of challenge infection resulted in a partial but significant reduction of recovery of adult worms. Induction of eosinophilia by an oral administration of embryonated eggs of Toxocara canis prior to challenge infection enhanced the reduction.