Optimizing HIV-1-specific CD8+ T-cell induction by recombinant BCG in prime-boost regimens with heterologous viral vectors
| Autor: | Alice Mbewe-Mvula, Gerald W. Both, Anne Bridgeman, Tomáš Hanke, Jerald C. Sadoff, Richard Hopkins, Joan Joseph, John Fulkerson, Charles Bourne |
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| Rok vydání: | 2011 |
| Předmět: |
Immunogen
Genetic Vectors Immunology Immunization Secondary Epitopes T-Lymphocyte Heterologous HIV Infections CD8-Positive T-Lymphocytes Biology complex mixtures Adenoviridae law.invention Viral vector Mice Immune system law Animals Immunology and Allergy Cytotoxic T cell AIDS Vaccines Mice Inbred BALB C Vaccines Synthetic Sheep Vaccination Viral Vaccines Atadenovirus Virology Bacterial vaccine BCG Vaccine HIV-1 Recombinant DNA Female Immunization CD8 Signal Transduction |
| Zdroj: | European Journal of Immunology. 41:3542-3552 |
| ISSN: | 0014-2980 |
| Popis: | The desire to induce HIV-1-specific responses soon after birth to prevent breast milk transmission of HIV-1 led us to propose a vaccine regimen which primes HIV-1-specific T cells using a recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) vaccine. Because attenuated live bacterial vaccines are typically not sufficiently immunogenic as stand-alone vaccines, rBCG-primed T cells will likely require boost immunization(s). Here, we compared modified Danish (AERAS-401) and Pasteur lysine auxotroph (222) strains of BCG expressing the immunogen HIVA for their potency to prime HIV-1-specific responses in adult BALB/c mice and examined four heterologous boosting HIVA vaccines for their immunogenic synergy. We found that both BCG.HIVA 401 and BCG.HIVA 222 primed HIV-1-specific CD8 + T-cell-mediated responses. The strongest boosts were delivered by human adenovirus-vectored HAdV5.HIVA and sheep atadenovirus-vectored OAdV7.HIVA vaccines, followed by poxvirus MVA.HIVA; the weakest was plasmid pTH.HIVA DNA. The prime-boost regimens induced T cells capable of efficient in vivo killing of sensitized target cells. We also observed that the BCG.HIVA 401 and BCG.HIVA 222 vaccines have broadly similar immunologic properties, but display a number of differences mainly detected through distinct profiles of soluble intercellular signaling molecules produced by immune splenocytes in response to both HIV-1- and BCG-specific stimuli. These results encourage further development of the rBCG prime-boost regimen. © 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim. |
| Databáze: | OpenAIRE |
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