DNA vaccines expressing different forms of simian immunodeficiency virus antigens decrease viremia upon SIVmac251 challenge
| Autor: | Patricia Roth, Margherita Rosati, Agneta von Gegerfelt, George N. Pavlakis, David Venzon, Candido Alicea, Marjorie Robert-Guroff, Phil Markham, Antonio Valentin, Barbara K. Felber, David C. Montefiori |
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| Rok vydání: | 2005 |
| Předmět: |
HIV Antigens
viruses Immunology Viremia Biology medicine.disease_cause Antibodies Viral Lymphocyte Activation Microbiology Virus DNA vaccination Cell Line Virology Vaccines and Antiviral Agents medicine Vaccines DNA Animals Humans AIDS Vaccines Immunogenicity Simian immunodeficiency virus medicine.disease Fusion protein Macaca mulatta Insect Science Simian Immunodeficiency Virus Viral load |
| Zdroj: | Journal of virology. 79(13) |
| ISSN: | 0022-538X |
| Popis: | We have tested the efficacy of DNA immunization as a single vaccination modality for rhesus macaques followed by highly pathogenic SIVmac251 challenge. To further improve immunogenicity of the native proteins, we generated expression vectors producing fusion of the proteins Gag and Env to the secreted chemokine MCP3, targeting the viral proteins to the secretory pathway and to a β-catenin (CATE) peptide, targeting the viral proteins to the intracellular degradation pathway. Macaques immunized with vectors expressing the MCP3-tagged fusion proteins developed stronger antibody responses. Following mucosal challenge with pathogenic SIVmac251, the vaccinated animals showed a statistically significant decrease in viral load (P= 0.010). Interestingly, macaques immunized with a combination of vectors expressing three forms of antigens (native protein and MCP3 and CATE fusion proteins) showed the strongest decrease in viral load (P= 0.0059). Postchallenge enzyme-linked immunospot values for Gag and Env as well asgag-specific T-helper responses correlated with control of viremia. Our data show that the combinations of DNA vaccines producing native and modified forms of antigens elicit more balanced immune responses able to significantly reduce viremia for a long period (8 months) following pathogenic challenge with SIVmac251. |
| Databáze: | OpenAIRE |
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