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
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:
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