Reduction of Simian-Human Immunodeficiency Virus 89.6P Viremia in Rhesus Monkeys by Recombinant Modified Vaccinia Virus Ankara Vaccination
| Autor: | Rebekah Zin, Linda S. Wyatt, David C. Montefiori, Michelle A. Lifton, Marcelo J. Kuroda, Alicia Buckler-White, Dan H. Barouch, Vanessa M. Hirsch, Alicia Gaitan, Jörn E. Schmitz, Sampa Santra, Jae-Hwan Nam, Ronald J. Plishka, Norman L. Letvin, Bernard Moss, Christine E. Nickerson |
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| Rok vydání: | 2001 |
| Předmět: |
CD4-Positive T-Lymphocytes
Time Factors viruses Immunology Simian Acquired Immunodeficiency Syndrome Gene Products gag Gene Products pol Vaccinia virus Viremia Antibodies Viral Microbiology Virus chemistry.chemical_compound Immune system Immunity Virology Vaccines and Antiviral Agents medicine Animals Humans Cytotoxic T cell Neutralizing antibody Vaccines Synthetic biology Gene Products env virus diseases medicine.disease Macaca mulatta CD4 Lymphocyte Count CTL chemistry Insect Science Disease Progression HIV-1 biology.protein RNA Viral Simian Immunodeficiency Virus Vaccinia T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of Virology. 75:5151-5158 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Since cytotoxic T lymphocytes (CTLs) are critical for controlling human immunodeficiency virus type 1 (HIV-1) replication in infected individuals, candidate HIV-1 vaccines should elicit virus-specific CTL responses. In this report, we study the immune responses elicited in rhesus monkeys by a recombinant poxvirus vaccine and the degree of protection afforded against a pathogenic simian-human immunodeficiency virus SHIV-89.6P challenge. Immunization with recombinant modified vaccinia virus Ankara (MVA) vectors expressing SIVmac239gag-poland HIV-1 89.6envelicited potent Gag-specific CTL responses but no detectable SHIV-specific neutralizing antibody (NAb) responses. Following intravenous SHIV-89.6P challenge, sham-vaccinated monkeys developed low-frequency CTL responses, low-titer NAb responses, rapid loss of CD4+T lymphocytes, high-setpoint viral RNA levels, and significant clinical disease progression and death in half of the animals by day 168 postchallenge. In contrast, the recombinant MVA-vaccinated monkeys demonstrated high-frequency secondary CTL responses, high-titer secondary SHIV-89.6-specific NAb responses, rapid emergence of SHIV-89.6P-specific NAb responses, partial preservation of CD4+T lymphocytes, reduced setpoint viral RNA levels, and no evidence of clinical disease or mortality by day 168 postchallenge. There was a statistically significant correlation between levels of vaccine-elicited CTL responses prior to challenge and the control of viremia following challenge. These results demonstrate that immune responses elicited by live recombinant vectors, although unable to provide sterilizing immunity, can control viremia and prevent disease progression following a highly pathogenic AIDS virus challenge. |
| Databáze: | OpenAIRE |
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