Objective Although HCV is a major cause of chronic liver disease worldwide, there is currently no prophylactic vaccine for this virus. Thus, the development of an HCV vaccine that can induce both humoural and cellular immunity is urgently needed. To create an effective HCV vaccine, we evaluated neutralising antibody induction and cellular immune responses following the immunisation of a non-human primate model with cell culture-generated HCV (HCVcc).
Design To accomplish this, 10 common marmosets were immunised with purified, inactivated HCVcc in combination with two different adjuvants: the classically used aluminum hydroxide (Alum) and the recently established adjuvant: CpG oligodeoxynucleotide (ODN) wrapped by schizophyllan (K3-SPG).
Results The coadministration of HCVcc with K3-SPG efficiently induced immune responses against HCV, as demonstrated by the production of antibodies with specific neutralising activity against chimaeric HCVcc with structural proteins from multiple HCV genotypes (1a, 1b, 2a and 3a). The induction of cellular immunity was also demonstrated by the production of interferon-γ mRNA in spleen cells following stimulation with the HCV core protein. These changes were not observed following immunisation with HCVcc/Alum preparation. No vaccination-related abnormalities were detected in any of the immunised animals.
Conclusions The current preclinical study demonstrated that a vaccine included both HCVcc and K3-SPG induced humoural and cellular immunity in marmosets. Vaccination with this combination resulted in the production of antibodies exhibiting cross-neutralising activity against multiple HCV genotypes. Based on these findings, the vaccine created in this study represents a promising, potent and safe prophylactic option against HCV.
- INFECTIOUS DISEASE
- CELLULAR IMMUNITY
- IMMUNE RESPONSE
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Contributors TW, HA and TK designed the study. HY, AH, SS, MM, NN, TS, RS and KI performed the study. KK and KJI provided the adjuvant and instructed the procedures. HY, HA and TK wrote the manuscript.
Funding This work was supported by grants for Scientific Research from the Ministry of Health, Labour and Welfare of Japan (H23-seisakutansaku-ippan-002) and for Research Programs on Development of New Drugs (15ak0101002h0005) and Hepatitis (15fk0310011h0104) from Japan Agency for Medical Research and Development, AMED.
Competing interests HY, MM, NN and TS are employee of Toray Industries.
Provenance and peer review Not commissioned; externally peer reviewed.
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