Gp120/CD4 blocking antibodies are frequently elicited in ART-naïve chronically HIV-1 infected individuals
Carrillo, Jorge (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Molinos-Albert, Luis Manuel (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Rodríguez de la Concepción, María Luisa (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Marfil, Sílvia (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
García Rodríguez, Elisabet (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Derking, Ronald (University of Amsterdam)
Sanders, Rogier W. (University of Amsterdam)
Clotet Sala, Bonaventura (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Blanco, Julià (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Universitat Autònoma de Barcelona

Fecha:	2015
Resumen:	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.
Ayudas:	Instituto de Salud Carlos III FIS/PI1102089
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Enzyme-linked immunoassays ; Antibodies ; Flow cytometry ; HIV-1 ; Recombinant proteins ; Glycoproteins ; Antibody response ; Cell staining
Publicado en:	PloS one, Vol. 10, No. 3 (March 2015) , p. e0120648, ISSN 1932-6203

DOI: 10.1371/journal.pone.0120648
PMID: 25803681

18 p, 1.7 MB

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