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A heterologous prime/boost vaccination strategy enhances the immunogenicity of therapeutic vaccines for hepatitis C virus.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2013 Sep; Vol. 208 (6), pp. 1008-19. Date of Electronic Publication: 2013 Jun 17. - Publication Year :
- 2013
-
Abstract
- Background: We explored the concept of heterologous prime/boost vaccination using 2 therapeutic vaccines currently in clinical development aimed at treating chronically infected hepatitis C virus (HCV) patients: prime with a DNA-based vaccine expressing HCV genotype 1a NS3/4A proteins (ChronVac-C) and boost with a modified vaccinia virus Ankara vaccine expressing genotype 1b NS3/4/5B proteins (MVATG16643).<br />Methods: Two ChronVac-C immunizations 4 weeks apart were delivered intramuscularly in combination with in vivo electroporation and subsequently 5 or 12 weeks later boosted by 3 weekly subcutaneous injections of MVATG16643. Two mouse strains were used, and we evaluated quality, magnitude, and functionality of the T cells induced.<br />Results: DNA prime/MVA boost regimen induced significantly higher levels of interferon γ (IFN-γ) or interleukin 2 (IL-2) ELISpot responses compared with each vaccine alone, independent of the time of analysis and the time interval between vaccinations. Both CD8⁺ and CD4⁺ T-cell responses as well as the spectrum of epitopes recognized was improved. A significant increase in polyfunctional IFN-γ/tumor necrosis factor α (TNF-α)/CD107a⁺ CD8⁺ T cells was detected following ChronVac-C/MVATG16643 vaccination (from 3% to 25%), and prime/boost was the only regimen that activated quadrifunctional T cells (IFN-γ/TNF-α/CD107a/IL-2). In vivo functional protective capacity of DNA prime/MVA boost was demonstrated in a Listeria-NS3-1a challenge model.<br />Conclusions: We provide a proof-of-concept that immunogenicity of 2 HCV therapeutic vaccines can be improved using their combination, which merits further clinical development.
- Subjects :
- Animals
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Genotype
Hepacivirus
Hepatitis C immunology
Immunization, Secondary
Interferon-gamma blood
Interleukin-2 blood
Mice
Mice, Inbred C57BL
Mice, Transgenic
Tumor Necrosis Factor-alpha blood
Vaccines, DNA immunology
Viral Hepatitis Vaccines genetics
Antibody Formation
Hepatitis C prevention & control
Vaccination methods
Viral Hepatitis Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 208
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 23776192
- Full Text :
- https://doi.org/10.1093/infdis/jit267