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Induction of humoural and cellular immunity by immunisation with HCV particle vaccine in a non-human primate model
  1. Hiroshi Yokokawa1,2,
  2. Atsunori Higashino3,4,
  3. Saori Suzuki3,4,
  4. Masaki Moriyama1,
  5. Noriko Nakamura1,
  6. Tomohiko Suzuki1,
  7. Ryosuke Suzuki2,
  8. Koji Ishii2,
  9. Kouji Kobiyama5,6,
  10. Ken J Ishii5,6,
  11. Takaji Wakita2,
  12. Hirofumi Akari3,4,
  13. Takanobu Kato2
  1. 1 Pharmaceutical Research Laboratories, Toray Industries, Inc, Kanagawa, Japan
  2. 2 Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
  3. 3 Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, Inuyama, Japan
  4. 4 Laboratory of Infectious Disease Model, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
  5. 5 Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
  6. 6 Laboratory of Vaccine Science, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Osaka, Japan
  1. Correspondence to Dr Takanobu Kato, Department of Virology II, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan; takato{at} and Dr Hirofumi Akari, Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama 484-8506, Japan; akari.hirofumi.5z{at}


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.

  • HCV

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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.