Design and pre-clinical evaluation of a universal HIV-1 vaccine

• Published in: PloS one 2007-10, Vol.2 (10), p.e984-e984
• Main Authors: Létourneau, Sven, Im, Eung-Jun, Mashishi, Tumelo, Brereton, Choechoe, Bridgeman, Anne, Yang, Hongbing, Dorrell, Lucy, Dong, Tao, Korber, Bette, McMichael, Andrew J, Hanke, Tomás
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adenoviruses; AIDS; AIDS vaccines; AIDS Vaccines - therapeutic use; Animals; Antigenic determinants; CD4 antigen; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - metabolism; Cloning; Conserved sequence; Councils; Cytotoxicity; Deoxyribonucleic acid; Design; Development and progression; DNA; DNA vaccines; Drug Design; Drug Evaluation, Preclinical; Epitopes; Epitopes - chemistry; Expression vectors; Genes, Viral; Genetic vectors; Health aspects; HIV; HIV-1 - metabolism; Human immunodeficiency virus; Humans; Immunological memory; Immunology; Immunology/Antigen Processing and Recognition; Immunology/Immune Response; Immunology/Immunity to Infections; Infectious Diseases/HIV Infection and AIDS; Interferon-gamma - metabolism; Leukocytes, Mononuclear - metabolism; Lymphocytes; Lymphocytes T; Medical research; Medicine; Memory cells; Mice; Mice, Inbred BALB C; Mycobacterium bovis; Plasmids; Proteomes; Spleen - cytology; T cell receptors; T cells; Test procedures; Vaccines; Virology/Vaccines; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0000984

One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test. To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIV(CONSV), by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, C and D, which alternate to ensure equal clade coverage. The gene coding for the HIV(CONSV) protein was inserted into the three most studied vaccine vectors, plasmid DNA, human adenovirus serotype 5 and modified vaccine virus Ankara (MVA), and induced HIV-1-specific T cell responses in mice. We also demonstrated that these conserved regions prime CD8(+) and CD4(+) T cell to highly conserved epitopes in humans and that these epitopes, although usually subdominant, generate memory T cells in patients during natural HIV-1 infection. Therefore, this vaccine approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape. Furthermore, this approach has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity.