Epitope enhancement of a CD4 HIV epitope toward the development of the next generation HIV vaccine

Virus-specific CD4+ T cell help and CD8+ cytotoxic T cell responses are critical for maintenance of effective immunity in chronic viral infections. The importance of CD4+ T cells has been documented in HIV infection. To investigate whether a stronger CD4+ T cell response can be induced by modificati...

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Bibliographic Details
Authors: Okazaki, T. (Takahiro)|||/items/82cc1ccf-3532-429c-b864-a0fba10a2b66, Pendleton, C.D. (C. David)|||/items/d771a43c-8d86-4aa3-b7af-3ce46eac4085, Sarobe, P. (Pablo)|||/items/e6f6a7ac-cfe2-409e-ab14-057dea5fd160, Thomas, E.K. (Elaine K.)|||/items/09733bb8-737d-4838-bace-bc27bc14d24c, Iyengar, S. (Sujatha)|||/items/3dd3c327-2b27-46a7-9eb0-79cfc4b3a6c8, Harro, C. (Clayton)|||/items/fd11f9ec-33a2-4b3e-9e65-94918fe698b8, Schwartz, D. (David)|||/items/38b2a216-d9cd-4649-abdf-72e9312ead20, Berzofsky, J.A. (Jay A.)|||/items/946d4d79-e6de-45b6-ae2a-7c159e8a044f
Format: article
Publication Date:2006
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/21664
Online Access:https://hdl.handle.net/10171/21664
Access Level:Open access
Keyword:AIDS Vaccines/chemistry
AIDS Vaccines/immunology
CD4-Positive T-Lymphocytes/immunology
Epitopes, T-Lymphocyte/chemistry
Epitopes, T-Lymphocyte/immunology
HIV-1/immunology
Description
Summary:Virus-specific CD4+ T cell help and CD8+ cytotoxic T cell responses are critical for maintenance of effective immunity in chronic viral infections. The importance of CD4+ T cells has been documented in HIV infection. To investigate whether a stronger CD4+ T cell response can be induced by modifications to enhance the T1 epitope, the first CD4+ T cell epitope discovered in HIV-1-gp120, we developed a T1-specific CD4+ T cell line from a healthy volunteer immunized with a canarypox vector expressing gp120 and boosted with recombinant gp120. This T1-specific CD4+ T cell line was restricted to DR13, which is common in U.S. Caucasians and African-Americans and very frequent in Africans. Peptides with certain amino acid substitutions in key positions induced enhanced specific CD4+ T cell proliferative responses at lower peptide concentration than the original epitope. This relatively conserved CD4 epitope improved by the epitope enhancement strategy could be a component of a more effective second generation vaccine construct for HIV infection.