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Título:
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Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals
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Autor/a:
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Molinos-Albert, Luis M.; Carrillo, Jorge; Curriu, Marta; Rodríguez de la Concepción, Maria L.; Marfil, Sílvia; García, Elisabet; Clotet, Bonaventura; Blanco, Julià
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Otros autores:
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Universitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades |
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Notas:
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Background
The MPER region of the HIV-1 envelope glycoprotein gp41 is targeted by broadly neutralizing antibodies. However, the localization of this epitope in a hydrophobic environment seems to hamper the elicitation of these antibodies in HIV infected individuals.
We have quantified and characterized anti-MPER antibodies by ELISA and by flow cytometry using a collection of mini gp41-derived proteins expressed on the surface of 293T cells. Longitudinal plasma samples from 35 HIV-1 infected individuals were assayed for MPER recognition and MPER-dependent neutralizing capacity using HIV-2 viruses engrafted with HIV-1 MPER sequences.
Results
Miniproteins devoid of the cysteine loop of gp41 exposed the MPER on 293T cell membrane. Anti-MPER antibodies were identified in most individuals and were stable when analyzed in longitudinal samples. The magnitude of the responses was strongly correlated with the global response to the HIV-1 envelope glycoprotein, suggesting no specific limitation for anti-MPER antibodies. Peptide mapping showed poor recognition of the C-terminal MPER moiety and a wide presence of antibodies against the 2F5 epitope. However, antibody titers failed to correlate with 2F5-blocking activity and, more importantly, with the specific neutralization of HIV-2 chimeric viruses bearing the HIV-1 MPER sequence; suggesting a strong functional heterogeneity in anti-MPER humoral responses.
Conclusions
Anti-MPER antibodies can be detected in the vast majority of HIV-1 infected individuals and are generated in the context of the global anti-Env response. However, the neutralizing capacity is heterogeneous suggesting that eliciting neutralizing anti-MPER antibodies by immunization might require refinement of immunogens to skip nonneutralizing responses. |
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Materia(s):
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-Sida -- Tractament |
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Derechos:
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Aquest document està subjecte a aquesta llicència Creative Commons
http://creativecommons.org/licenses/by/3.0/es/
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Tipo de documento:
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Artículo
info:eu-repo/publishedVersion |
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Editor:
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Biomed central
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