J Virol. 2013 Jul;87(13):7282-300

Gómez CE, Perdiguero B, Cepeda MV, Mingorance L, García-Arriaza J, Vandermeeren A, Sorzano CO, Esteban M.

A major goal in the control of hepatitis C infection is the development of a vaccine. Here, we have developed a novel HCV vaccine candidate based on the highly attenuated poxvirus vector MVA (referred as MVA-HCV) expressing the near full-length (7.9 kbp) HCV sequence, with the aim to target almost all of the T and B cell determinants described for HCV.

In infected cells, MVA-HCV produces a polyprotein that is subsequently processed into the structural and nonstructural HCV proteins, triggering the cytoplasmic accumulation of dense membrane aggregates. In both C57BL/6 and transgenic HLA-A2 vaccinated mice, MVA-HCV induced high, broad, polyfunctional and long-lasting HCV-specific T cell immune responses. The vaccine-induced T cell response was mainly mediated by CD8 T cells; however, although lower in magnitude, the CD4+ T cells were highly polyfunctional. In homologous protocol (MVA-HCV/MVA-HCV) the main CD8+ T cell target was p7+NS2, whereas in heterologous combination (DNA-HCV/MVA-HCV) the main target was NS3. Antigenic responses were also detected against other HCV proteins (Core, E1-E2, NS4) but the magnitude of the responses was dependent of the protocol used. The majority of the HCV-induced CD8+ T cells were triple or quadruple-cytokine producers. The MVA-HCV vaccine induced memory CD8+ T cell responses with an effector memory (TEM) phenotype.

Overall, our data showed that MVA-HCV induced broad, highly polyfunctional and durable T cell responses of a magnitude and quality that might be associated with protective immunity and open the path for future considerations of MVA-HCV as prophylactic and/or therapeutic vaccine candidate against HCV.