Bibliographic Details
| Title: |
Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals. |
| Authors: |
Molinos-Albert, Luis M.1 lmmolinos@irsicaixa.es, Carrillo, Jorge1 jcarrillo@irsicaixa.es, Curriu, Marta1 marta.curriu@gmail.com, Rodriguez de la Concepción, Maria L.1 mlrodriguez@irsicaixa.es, Marfil, Silvia1 smarfil@irsicaixa.es, García, Elisabet1 egarcia@irsicaixa.es, Clotet, Bonaventura1,2 bclotet@irsicaixa.es, Blanco, Julià1,2 jblanco@irsicaixa.es |
| Source: |
Retrovirology. 2014, Vol. 11 Issue 1, p1-21. 21p. |
| Subject Terms: |
*GLYCOPROTEINS, *EPITOPES, *HIV-positive persons, *FLOW cytometry, *ENZYME-linked immunosorbent assay, *HIV, *MEMBRANE glycoproteins |
| Abstract: |
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 2 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. [ABSTRACT FROM AUTHOR] |
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