Safety and immunogenicity of DNA prime and modified vaccinia ankara virus-HIV subtype C vaccine boost in healthy adults
| Autor: | Angela Lombardo, Josephine H. Cox, Patricia E. Fast, Jill Gilmour, Brian Gazzard, Dilbinder K. Gill, Marta Boffito, Akil Jackson, Lorna Clark, Hannah Cheeseman, Amy W. Chung, Devika Zachariah, Dagna Laufer, Eddy Sayeed, Galit Alter, Peter Hayes, James Ackland, Jakub Kopycinski, Andrea von Lieven, Len Dally |
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| Rok vydání: | 2013 |
| Předmět: |
Microbiology (medical)
Adult Modified vaccinia Ankara Enzyme-Linked Immunospot Assay T-Lymphocytes Clinical Biochemistry Immunology Vaccinia virus Biology HIV Antibodies Group A complex mixtures Group B DNA vaccination Placebos chemistry.chemical_compound Interferon-gamma Vaccines DNA Immunology and Allergy Humans AIDS Vaccines Drug Carriers Vaccines Synthetic Vaccines Immunogenicity ELISPOT Vaccination HIV Virology chemistry Vaccinia |
| Zdroj: | Clinical and vaccine immunology : CVI. 20(3) |
| ISSN: | 1556-679X |
| Popis: | A randomized, double-blind, placebo-controlled phase I trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of 3 doses of DNA vaccine (Advax) plus 1 dose of recombinant modified vaccinia virus Ankara (MVA) (TBC-M4) or 3 doses of TBC-M4 alone (groups A and B, respectively). Both vaccine regimens were found to be safe and well tolerated. Gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay responses were detected in 1/10 (10%) individuals in group A after three Advax primes and in 9/9 individuals (100%) after the MVA boost. In group B, IFN-γ ELISPOT responses were detected in 6/12 (50%) and 7/11 (64%) individuals after the second and third MVA vaccinations, respectively. Responses to all vaccine components, but predominantly to Env, were seen. The breadth and magnitude of the T cell response and viral inhibition were greater in group A than in group B, indicating that the quality of the T-cell response was enhanced by the DNA prime. Intracellular cytokine staining indicated that the T-cell responses were polyfunctional but were skewed toward Env with a CD4+phenotype. At 2 weeks after the last vaccination, HIV-specific antibody responses were detected in all (100%) group B and 1/11 (9.1%) group A vaccinees. Vaccinia virus-specific responses were detected in all (100%) group B and 2/11 (18.2%) group A vaccinees. In conclusion, HIV-specific T-cell responses were seen in the majority of volunteers in groups A and B but with a trend toward greater quality of the T-cell response in group A. Antibody responses were better in group B than in group A. |
| Databáze: | OpenAIRE |
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