Gp120/CD4 blocking antibodies are frequently elicited in ART-naïve chronically HIV-1 infected individuals
Autor: | Elisabet García, Bonaventura Clotet, María Luisa Rodríguez de la Concepción, Silvia Marfil, Rogier W. Sanders, Jorge Carrillo, Ronald Derking, Julià Blanco, Luis M. Molinos-Albert |
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Přispěvatelé: | AII - Amsterdam institute for Infection and Immunity, Medical Microbiology and Infection Prevention, Universitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades |
Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
lcsh:Medicine
HIV Infections HIV Antibodies HIV Envelope Protein gp120 Virus Epitope Antibodies Blocking antibody VIH (Virus) Humans Flow cytometry Binding site Enzyme-linked immunoassays Antibodies Blocking lcsh:Science Glycoproteins chemistry.chemical_classification Recombinant proteins Multidisciplinary biology lcsh:R virus diseases Sida -- Tractament Primary and secondary antibodies Virology Antibodies Neutralizing Cell staining Titer chemistry Immunology CD4 Antigens Chronic Disease Antibody response biology.protein HIV-1 lcsh:Q Antibody Glycoprotein Research Article |
Zdroj: | PLoS ONE, Vol 10, Iss 3, p e0120648 (2015) PLoS ONE, 10(3). Public Library of Science Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona RIUVic. Repositorio Institucional de la Universidad de Vic PLoS ONE |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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