title: Anti-MPER antibodies with heterogeneous neutralization capacity are detectable in most untreated HIV-1 infected individuals.
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 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.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Molinos-Albert
authors.forename: Jorge
authors.initials: J
authors.lastname: Carrillo
authors.forename: Marta
authors.initials: M
authors.lastname: Curriu
authors.forename: Maria L
authors.initials: ML
authors.lastname: Rodriguez de la Concepción
authors.forename: Silvia
authors.initials: S
authors.lastname: Marfil
authors.forename: Elisabet
authors.initials: E
authors.lastname: García
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.affiliation: IrsiCaixa-HIVACAT, Institut de Recerca en Ciències de la Salut Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, UAB, Badalona, 08916 Barcelona, Catalonia, Spain. jblanco@irsicaixa.es.
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods; D009500:Neutralization Tests / Q000379:methods
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1