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Potent HIV-1-Specific CD8 T Cell Responses Induced in Mice after Priming with a Multiepitopic DNA-TMEP and Boosting with the HIV Vaccine MVA-B.
- Source :
-
Viruses [Viruses] 2018 Aug 13; Vol. 10 (8). Date of Electronic Publication: 2018 Aug 13. - Publication Year :
- 2018
-
Abstract
- An effective vaccine against Human Immunodeficiency Virus (HIV) still remains the best solution to provide a sustainable control and/or eradication of the virus. We have previously generated the HIV-1 vaccine modified vaccinia virus Ankara (MVA)-B, which exhibited good immunogenicity profile in phase I prophylactic and therapeutic clinical trials, but was unable to prevent viral rebound after antiretroviral (ART) removal. To potentiate the immunogenicity of MVA-B, here we described the design and immune responses elicited in mice by a new T cell multi-epitopic B (TMEP-B) immunogen, vectored by DNA, when administered in homologous or heterologous prime/boost regimens in combination with MVA-B. The TMEP-B protein contained conserved regions from Gag, Pol, and Nef proteins including multiple CD4 and CD8 T cell epitopes functionally associated with HIV control. Heterologous DNA-TMEP/MVA-B regimen induced higher HIV-1-specific CD8 T cell responses with broader epitope recognition and higher polyfunctional profile than the homologous DNA-TMEP/DNA-TMEP or the heterologous DNA-GPN/MVA-B combinations. Moreover, higher HIV-1-specific CD4 and Tfh immune responses were also detected using this regimen. After MVA-B boost, the magnitude of the anti-VACV CD8 T cell response was significantly compromised in DNA-TMEP-primed animals. Our results revealed the immunological potential of DNA-TMEP prime/MVA-B boost regimen and supported the application of these combined vectors in HIV-1 prevention and/or therapy.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- AIDS Vaccines administration & dosage
Animals
Female
Genetic Vectors
HIV Antigens immunology
HIV Infections prevention & control
HIV-1
Immunization, Secondary
Mice
Mice, Inbred BALB C
Vaccines, DNA immunology
Vaccinia virus
AIDS Vaccines immunology
CD8-Positive T-Lymphocytes immunology
Epitopes, T-Lymphocyte immunology
HIV Infections immunology
Immunogenicity, Vaccine
Subjects
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 10
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 30104537
- Full Text :
- https://doi.org/10.3390/v10080424