Protection against Mucosal SIVsmChallenge in Macaques Infected with a Chimeric SIV that Expresses HIV Type 1 Envelope
Autor: | Per Putkonen, Rigmor Thorstensson, Barbro Mäkitalo, Gunnel Biberfeld, Yi-Jun Zhang, Marlene Quesada-Rolander, Esmeralda Castaños-Velez |
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Rok vydání: | 1996 |
Předmět: |
viruses
animal diseases Immunology Simian Acquired Immunodeficiency Syndrome Active immunization medicine.disease_cause Genes env Macaque Virus Microbiology Viral envelope Virology biology.animal medicine Animals Blood Transfusion Immunity Mucosal Acquired Immunodeficiency Syndrome Attenuated vaccine biology Chimera Antibody titer virus diseases Simian immunodeficiency virus CD4 Lymphocyte Count Disease Models Animal Macaca fascicularis Infectious Diseases Antibody Formation HIV-1 biology.protein Simian Immunodeficiency Virus Antibody T-Lymphocytes Cytotoxic |
Zdroj: | AIDS Research and Human Retroviruses. 12:993-999 |
ISSN: | 1931-8405 0889-2229 |
DOI: | 10.1089/aid.1996.12.993 |
Popis: | In a monkey model we used a chimeric SIV expressing the HIV-1 envelope gene (SHIV-4) as a live attenuated vaccine and a virulent SIVsm as a mucosal challenge. Four cynomolgus monkeys were inoculated intravenously with SHIV-4. Virus was repeatedly isolated from blood mononuclear cells of all four animals for 2 to 7 months after the inoculation of SHIV. All monkeys developed neutralizing antibodies to HIV-1 and high antibody titers to HIV-1 envelope glycoproteins. In contrast, no neutralizing antibodies to SIVsm were detected and cross-reacting antibodies to SIV envelope glycoproteins were demonstrable in low titers. Nine to 12 months after the SHIV inoculation the four monkeys and six naive control monkeys were challenged intrarectally with 10 monkey infectious doses of macaque cell-grown SIVsm. After a follow-up period of 1 year, two of four SHIV-infected monkeys were completely protected against SIVsm infection as shown by repeated negative virus isolations and negative polymerase chain reaction for SIV envelope DNA. One naive monkey that received blood from the two protected monkeys showed no signs of infection. The remaining two SHIV-infected monkeys showed an initial infection on challenge with SIVsm, but viral replication was thereafter suppressed. Cytotoxic T lymphocytes to SIV Nef and RT were demonstrable in one of four SHIV-infected monkeys before SIVsm challenge, but this monkey was not protected against SIV infection. All six control animals yielded virus repeatedly after SIVsm challenge and three of them showed declining CD4 cell counts. Thus, infection with SHIV expressing HIV-1 envelope could induce cross-protection against mucosal SIVsm challenge. |
Databáze: | OpenAIRE |
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