1. Immunogenicity of a Human Immunodeficiency Virus (HIV) Polytope Vaccine Containing Multiple HLA A2 HIV CD8+ Cytotoxic T-Cell Epitopes
- Author
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Luis Mateo, Andreas Suhrbier, Tonia Woodberry, Damon P. Eisen, Hüseyin Firat, François A. Lemonnier, Jill Medveczky, Rosemary A. Ffrench, Scott Thomson, Joy Gardner, Ian A. Ramshaw, and Suzanne L. Elliott
- Subjects
Transcription, Genetic ,Immunology ,Molecular Sequence Data ,Epitopes, T-Lymphocyte ,Gene Products, gag ,Gene Products, pol ,chemical and pharmacologic phenomena ,HIV Infections ,Mice, Transgenic ,Human leukocyte antigen ,Biology ,CD8-Positive T-Lymphocytes ,Microbiology ,Epitope ,Gene Products, nef ,Cell Line ,Mice ,Virology ,Vaccines and Antiviral Agents ,HLA-A2 Antigen ,Cytotoxic T cell ,Animals ,Humans ,Amino Acid Sequence ,nef Gene Products, Human Immunodeficiency Virus ,HIV vaccine ,AIDS Vaccines ,Base Sequence ,Immunogenicity ,HIV ,CTL ,Insect Science ,CD8 ,T-Lymphocytes, Cytotoxic - Abstract
Compelling evidence now suggests that αβ CD8 cytotoxic T lymphocytes (CTL) have an important role in preventing human immunodeficiency virus (HIV) infection and/or slowing progression to AIDS. Here, we describe an HIV type 1 CTL polyepitope, or polytope, vaccine comprising seven contiguous minimal HLA A2-restricted CD8 CTL epitopes conjoined in a single artificial construct. Epitope-specific CTL lines derived from HIV-infected individuals were able to recognize every epitope within the construct, and HLA A2-transgenic mice immunized with a recombinant virus vaccine coding for the HIV polytope also generated CTL specific for different epitopes. Each epitope in the polytope construct was therefore processed and presented, illustrating the feasibility of the polytope approach for HIV vaccine design. By simultaneously inducing CTL specific for different epitopes, an HIV polytope vaccine might generate activity against multiple challenge isolates and/or preempt the formation of CTL escape mutants.
- Published
- 1999