Robert Thaï

Publications (2)9.55 Total impact

• Article: Stabilization of HIV-1 envelope in the CD4-bound conformation through specific cross-linking of a CD4 mimetic.

  Grégoire Martin, Brian Burke, Robert Thaï, Antu K Dey, Olivier Combes, Oscar H P Ramos, Bernadette Heyd, Anthony R Geonnotti, David C Montefiori, Elaine Kan, Ying Lian, Yide Sun, Toufik Abache, Jeffrey B Ulmer, Hocine Madaoui, Raphaël Guérois, Susan W Barnett, Indresh K Srivastava, Pascal Kessler, Loïc Martin
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  ABSTRACT: CD4 binding on gp120 leads to the exposure of highly conserved regions recognized by the HIV co-receptor CCR5 and by CD4-induced (CD4i) antibodies. A covalent gp120-CD4 complex was shown to elicit CD4i antibody responses in monkeys, which was correlated with control of the HIV virus infection (DeVico, A., Fouts, T., Lewis, G. K., Gallo, R. C., Godfrey, K., Charurat, M., Harris, I., Galmin, L., and Pal, R. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 17477-17482). Because the inclusion of CD4 in a vaccine formulation should be avoided, due to potential autoimmune reactions, we engineered small sized CD4 mimetics (miniCD4s) that are poorly immunogenic and do not induce anti-CD4 antibodies. We made covalent complexes between such an engineered miniCD4 and gp120 or gp140, through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5. In addition, they elicit CD4i antibody responses in rabbits and therefore represent potential vaccine candidates that mimic an important HIV fusion intermediate, without autoimmune hazard.
  Journal of Biological Chemistry 06/2011; 286(24):21706-16. · 4.77 Impact Factor
• Article: Stabilization of HIV-1 envelope in the CD4-bound conformation through specific crosslinking of a CD4 mimetic

  Grégoire Martin, Brian Burke, Robert Thaï, Antu K. Dey, Olivier Combes, Oscar H. P. Ramos, Bernadette Heyd, Anthony R. Geonnotti, David C. Montefiori, Elaine Kan, Ying Lian, Yide Sun, Toufik Abache, Martin L.
  [show abstract] [hide abstract]
  ABSTRACT: CD4 binding on gp120 leads to the exposure of highly conserved regions recognized by the HIV co-receptor CCR5 and by CD4-induced (CD4i) antibodies. A covalent gp120-CD4 complex was shown to elicit CD4i antibody responses in monkeys, which was correlated with control of the HIV virus infection (DeVico, A., Fouts, T., Lewis, G. K., Gallo, R. C., Godfrey, K., Charurat, M., Harris, I., Galmin, L., and Pal, R. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 17477–17482). Because the inclusion of CD4 in a vaccine formulation should be avoided, due to potential autoimmune reactions, we engineered small sized CD4 mimetics (miniCD4s) that are poorly immunogenic and do not induce anti-CD4 antibodies. We made covalent complexes between such an engineered miniCD4 and gp120 or gp140, through a site-directed coupling reaction. These complexes were recognized by CD4i antibodies as well as by the HIV co-receptor CCR5. In addition, they elicit CD4i antibody responses in rabbits and therefore represent potential vaccine candidates that mimic an important HIV fusion intermediate, without autoimmune hazard.
  Journal of Biological Chemistry 01/2011; 286:21706-16. · 4.77 Impact Factor