Gag-specific cytotoxic T-lymphocyte-based control of primary simian immunodeficiency virus replication in a vaccine trial
| Autor: | Hirofumi Akari, Tetsuo Tsukamoto, Hiroyuki Yamamoto, Chikaya Moriya, Kyoko Kurihara, Akiko Takeda, Miki Kawada, Tetsuro Matano, Nami Iwamoto, Hiroaki Takeuchi |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
viruses
Immunology Simian Acquired Immunodeficiency Syndrome Gene Products gag medicine.disease_cause Virus Replication Microbiology Virus T-Lymphocyte Subsets Virology Vaccines and Antiviral Agents medicine Animals Humans Point Mutation biology Vaccine trial SAIDS Vaccines Simian immunodeficiency virus Viral Load Vaccine efficacy biology.organism_classification Macaca mulatta CTL Viral replication Insect Science Lentivirus Simian Immunodeficiency Virus Viral load T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of virology. 82(20) |
| ISSN: | 1098-5514 |
| Popis: | Gag-specific cytotoxic T lymphocytes (CTLs) exert strong suppressive pressure on human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. However, it has remained unclear whether they can actually contain primary viral replication. Recent trials of prophylactic vaccines inducing virus-specific T-cell responses have indicated their potential to confer resistance against primary SIV replication in rhesus macaques, while the immunological determinant for this vaccine-based viral control has not been elucidated thus far. Here we present evidence implicating Gag-specific CTLs as responsible for the vaccine-based primary SIV control. Prophylactic vaccination using a Gag-expressing Sendai virus vector resulted in containment of SIVmac239 challenge in all rhesus macaques possessing the major histocompatibility complex (MHC) haplotype 90-120-Ia . In contrast, 90-120-Ia -positive vaccinees failed to contain SIVs carrying multiple gag CTL escape mutations that had been selected, at the cost of viral fitness, in SIVmac239-infected 90-120-Ia -positive macaques. These results show that Gag-specific CTL responses do play a crucial role in the control of wild-type SIVmac239 replication in vaccinees. This study implies the possibility of Gag-specific CTL-based primary HIV containment by prophylactic vaccination, although it also suggests that CTL-based AIDS vaccine efficacy may be abrogated in viral transmission between MHC-matched individuals. |
| Databáze: | OpenAIRE |
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