Abrogation of AIDS vaccine-induced cytotoxic T-lymphocyte efficacy in vivo due to a change in viral epitope flanking sequences
| Autor: | Tsugumine Shu, Chikaya Moriya, Akiko Takeda, Tetsuo Tsukamoto, Miki Kawada, Akihiro Iida, Tetsuro Matano, Yoshiyuki Nagai, Hiroyuki Yamamoto, Makoto Inoue, Mamoru Hasegawa, Hiroko Igarashi |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
viruses
Molecular Sequence Data Immunology Immunization Secondary Simian Acquired Immunodeficiency Syndrome Epitopes T-Lymphocyte Gene Products gag Virus Replication medicine.disease_cause Major histocompatibility complex Injections Intramuscular Microbiology Epitope Species Specificity Vaccines DNA medicine Animals Cytotoxic T cell Amino Acid Sequence Administration Intranasal Cells Cultured biology Vaccination SAIDS Vaccines Vaccine trial Simian immunodeficiency virus Vaccine efficacy Macaca mulatta Virology CTL Infectious Diseases Amino Acid Substitution Viral replication Leukocytes Mononuclear biology.protein Simian Immunodeficiency Virus T-Lymphocytes Cytotoxic |
| Zdroj: | Microbes and Infection. 10:285-292 |
| ISSN: | 1286-4579 |
| DOI: | 10.1016/j.micinf.2007.12.002 |
| Popis: | A current promising AIDS vaccine strategy is to elicit CD8(+) cytotoxic T lymphocyte (CTL) responses that broadly recognize highly-diversified HIVs. In our previous vaccine trial eliciting simian immunodeficiency virus (SIV) mac239 Gag-specific CTL responses, a group of Burmese rhesus macaques possessing a major histocompatibility complex haplotype 90-120-Ia have shown vaccine-based viral control against a homologous SIVmac239 challenge. Vaccine-induced Gag(206-216) epitope-specific CTL responses exerted strong selective pressure on the virus in this control. Here, we have evaluated in vivo efficacy of vaccine-induced Gag(206-216)-specific CTL responses in two 90-120-Ia-positive macaques against challenge with a heterologous SIVsmE543-3 that has the same Gag(206-216) epitope sequence with SIVmac239. Despite efficient Gag(206-216)-specific CTL induction by vaccination, both vaccinees failed to control SIVsmE543-3 replication and neither of them showed mutations within the Gag(206-216) epitope. Further analysis indicated that Gag(206-216)-specific CTLs failed to show responses against SIVsmE543-3 infection due to a change from aspartate to glutamate at Gag residue 205 immediately preceding the amino terminus of Gag(206-216) epitope. Our results suggest that even vaccine-induced CTL efficacy can be abrogated by a single amino acid change in viral epitope flanking region, underlining the influence of viral epitope flanking sequences on CTL-based AIDS vaccine efficacy. |
| Databáze: | OpenAIRE |
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