title: Gp120/CD4 blocking antibodies are frequently elicited in ART-naïve chronically HIV-1 infected individuals.
abstract: Antibodies with the ability to block the interaction of HIV-1 envelope glycoprotein (Env) gp120 with CD4, including those overlapping the CD4 binding site (CD4bs antibodies), can protect from infection by HIV-1, and their elicitation may be an interesting goal for any vaccination strategy. To identify gp120/CD4 blocking antibodies in plasma samples from HIV-1 infected individuals we have developed a competitive flow cytometry-based functional assay. In a cohort of treatment-naïve chronically infected patients, we showed that gp120/CD4 blocking antibodies were frequently elicited (detected in 97% plasma samples) and correlated with binding to trimeric HIV-1 envelope glycoproteins. However, no correlation was observed between functional CD4 binding blockade data and titer of CD4bs antibodies determined by ELISA using resurfaced gp120 proteins. Consistently, plasma samples lacking CD4bs antibodies were able to block the interaction between gp120 and its receptor, indicating that antibodies recognizing other epitopes, such as PGT126 and PG16, can also play the same role. Antibodies blocking CD4 binding increased over time and correlated positively with the capacity of plasma samples to neutralize the laboratory-adapted NL4.3 and BaL virus isolates, suggesting their potential contribution to the neutralizing workforce of plasma in vivo. Determining whether this response can be boosted to achieve broadly neutralizing antibodies may provide valuable information for the design of new strategies aimed to improve the anti-HIV-1 humoral response and to develop a successful HIV-1 vaccine.
authors: Institut de Recerca de la SIDA-IrsiCaixa-HIVACAT, Badalona, Barcelona, Spain.
authors: Jorge
authors: J
authors: Carrillo
authors: Institut de Recerca de la SIDA-IrsiCaixa-HIVACAT, Badalona, Barcelona, Spain; Institut de Recerca en Ciències de la Salut Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors: Luis Manuel
authors: LM
authors: Molinos-Albert
authors: Institut de Recerca de la SIDA-IrsiCaixa-HIVACAT, Badalona, Barcelona, Spain.
authors: Maria Luisa
authors: ML
authors: Rodríguez de la Concepción
authors: Institut de Recerca de la SIDA-IrsiCaixa-HIVACAT, Badalona, Barcelona, Spain.
authors: Silvia
authors: S
authors: Marfil
authors: Institut de Recerca de la SIDA-IrsiCaixa-HIVACAT, Badalona, Barcelona, Spain.
authors: Elisabet
authors: E
authors: García
authors: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Ronald
authors: R
authors: Derking
authors: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, United States of America.
authors: Rogier W
authors: RW
authors: Sanders
authors: Institut de Recerca de la SIDA-IrsiCaixa-HIVACAT, Badalona, Barcelona, Spain; Universitat Autònoma de Barcelona, Cerdanyola del Vallés, Barcelona, Spain; Universitat de Vic-Central de Catalunya, UVIC-UCC, Vic, Barcelona, Spain; Fundació Lluita contra la SIDA, Badalona, Barcelona, Spain.
authors: Bonaventura
authors: B
authors: Clotet
authors: Institut de Recerca de la SIDA-IrsiCaixa-HIVACAT, Badalona, Barcelona, Spain; Institut de Recerca en Ciències de la Salut Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; Universitat Autònoma de Barcelona, Cerdanyola del Vallés, Barcelona, Spain; Universitat de Vic-Central de Catalunya, UVIC-UCC, Vic, Barcelona, Spain.
authors: Julià
authors: J
authors: Blanco
mesh_terms: D019138:Antibodies, Blocking / Q000097:blood / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D002908:Chronic Disease; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans
chemical_list: D019138:Antibodies, Blocking; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120