Cross-protection in NYVAC–HIV-1-immunized/HIV-2-challenged but not in NYVAC–HIV-2-immunized/SHIV-challenged rhesus macaques
| Autor: | W G Alvord, Bo Peng, P. D. Markham, Genoveffa Franchini, Lalita C. Murty, James Tartaglia, Marjorie Robert-Guroff, Alash'le Abimiku, K Aldrich, L. J. Patterson, V. S. Kalyanaraman |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Cellular immunity Genetic Vectors Immunology Simian Acquired Immunodeficiency Syndrome HIV Infections Cross immunity Cross Reactions HIV Antibodies medicine.disease_cause Macaque biology.animal medicine Animals Immunology and Allergy AIDS Vaccines biology Poxviridae virus diseases Simian immunodeficiency virus biology.organism_classification Macaca mulatta Virology CTL Infectious Diseases HIV-2 Humoral immunity Lentivirus HIV-1 biology.protein RNA Viral Female Immunization Simian Immunodeficiency Virus Antibody T-Lymphocytes Cytotoxic |
| Zdroj: | AIDS. 14:2445-2455 |
| ISSN: | 0269-9370 |
| DOI: | 10.1097/00002030-200011100-00005 |
| Popis: | Objectives Immunization with attenuated poxvirus-HIV-1 recombinants followed by protein boosting had protected four of eight rhesus macaques from HIV-2SBL6669 challenge. The present study was designed to confirm this result and to conduct the reciprocal cross-protection experiment. Methods Twenty-four macaques were primed with NYVAC (a genetically attenuated Copenhagen vaccinia strain) recombinants with HIV-1 and HIV-2 env and gag-pol or NYVAC vector alone and boosted with homologous, oligomeric gp160 proteins or adjuvant only. Binding and neutralizing antibodies, cytotoxic T-lymphocytes (CTL) and CD8 T cell antiviral activity (CD8AA) were evaluated. One half of each immunization and control group were intravenously challenged with SHIV(HXB2) the other half was challenged with HIV-2SBL6669,. Protective outcome was assessed by monitoring virus isolation, proviral DNA and plasma viral RNA. Results Both immunization groups developed homologous binding antibodies; however, homologous neutralizing antibodies were only observed in NYVAC-HIV-2-immunized macaques. While no cross-reactive neutralizing antibodies were detected, both immunization groups displayed cross-reactive CTL. Significant CD8AA was observed for only one NYVAC-HIV-2-immunized macaque. Virological assessments verified that both NYVAC-HIV-1 and NYVAC-HIV-2 immunization significantly reduced viral burdens and partially protected against HIV-2 challenge, although cross-protection was not at the level that had been previously reported. Humoral antibody and/or CTL and CD8AA were associated with protection against homologous HIV-2 challenge, while cellular immune responses seemed more important for cross-protection. No significant protection was observed in the SHIV-challenged macaques, although NYVAC-HIV-1 immunization resulted in significantly lower viral burdens compared with controls. Conclusions Further delineation of cross-reactive mechanisms may aid in the development of a broadly protective vaccine. |
| Databáze: | OpenAIRE |
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