Effects of virus burden and chemokine expression on immunity to SHIV in nonhuman primates
| Autor: | Ilia Tikhonov, Paul M. Waterman, Glen S. Hatfield, Peter Evans, Joseph Bryant, Moiz Kitabwalla, Yichen Lu, C. David Pauza |
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| Rok vydání: | 2005 |
| Předmět: |
Chemokine
Immunology Simian Acquired Immunodeficiency Syndrome HIV Infections Biology HIV Antibodies Antibodies Viral Vaccines Attenuated Virus Replication Virus Immune system Antigen Immunity Virology Cytotoxic T cell Animals Humans AIDS Vaccines Recombination Genetic Vaccination Viral Load Macaca mulatta Titer biology.protein HIV-1 Molecular Medicine Simian Immunodeficiency Virus Antibody Chemokines |
| Zdroj: | Viral immunology. 17(4) |
| ISSN: | 0882-8245 |
| Popis: | HIV-1 vaccine candidates are designed to elicit Type 1 immune responses, including cytotoxic T cells and neutralizing antibodies. The type of immune response is influenced by many factors, including the levels of antigen expression and production of cytokines or chemokines; we designed a nonhuman primate study to evaluate the influence of these factors on protective immunity. Recombinant SHIV were engineered to express macrophage inflammatory protein-1 alpha (MIP-1alpha), regulated upon activation, normal T-cell expressed and secreted (RANTES), or Lymphotactin (Ltn) in place of nef in SHIV(89.6) (SHIV(89.6-MIP-1), SHIV(89.6-RANTES), SHIV(89.6-Ltn)). The parental virus SHIV(89.6) was included because it replicates to higher titer while still not causing disease. Control groups included animals that received a recombinant SHIV with a truncated chemokine construct (SHIV(89.6-dLtn)) and unvaccinated macaques. After pathogenic challenge with SHIV(89.6pd), animals from groups that received recombinant (nef-deleted) viruses had peak viremia levels three orders of magnitude lower than unvaccinated controls and increased survival times. Animals that received the original SHIV(89.6) (nef+) were highly resistant to both intrarectal and intravenous challenge with SHIV(89.6PD), and showed no signs of disease. There were no differences in survival times comparing unvaccinated and SHIV(89.6-dLtn) (control) groups, indicating that nef deleted viruses did not provide durable protection in this model. Strongest protection was seen in animals with the highest replicating virus (SHIV(89.6)), and the lower effect on survival after SHIV(89.6) nef-deleted vaccination, likely reflects differences in replication capacity. The protective effect of nef-deleted virus was partly restored by expressing Type 1 chemokines to augment viral immunity. |
| Databáze: | OpenAIRE |
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