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Original Article
A trivalent HCV vaccine elicits broad and synergistic polyclonal antibody response in mice and rhesus monkey
  1. Xuesong Wang1,2,3,
  2. Yu Yan1,3,
  3. Tianyu Gan1,3,
  4. Xi Yang3,4,
  5. Dapeng Li1,2,3,
  6. Dongming Zhou3,4,
  7. Qiang Sun3,5,
  8. Zhong Huang2,3,
  9. Jin Zhong1,3
  1. 1Unit of Viral Hepatitis, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
  2. 2Unit of Vaccinology and Antiviral Strategies, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
  3. 3University of Chinese Academy of Sciences, Beijing, China
  4. 4Vaccine Research Center, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
  5. 5Suzhou Non-human Primate Facility, Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
  1. Correspondence to Dr Jin Zhong, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; jzhong{at}ips.ac.cn and Dr Zhong Huang; huangzhong{at}ips.ac.cn

Abstract

Objective Despite the development of highly effective direct-acting antivirals, a prophylactic vaccine is needed for eradicating HCV. A major hurdle of HCV vaccine development is to induce immunity against HCV with high genome diversity. We previously demonstrated that a soluble E2 (sE2) expressed from insect cells induces broadly neutralising antibodies (NAbs) and prevents HCV infection. The objective of this study is to develop a multivalent HCV vaccine to increase the antigenic coverage.

Design We designed a trivalent vaccine containing sE2 from genotype 1a, 1b and 3a. Mice and rhesus macaques were immunised with monovalent or trivalent sE2 vaccine, and sera or purified immunoglobulin were assessed for neutralisation against a panel of cell culture-derived virion (HCVcc) of genotype 1–7 in cell culture. Splenocytes from the vaccinated macaques were assessed for HCV-specific T cell response.

Results We showed that the trivalent vaccine elicited pangenotypic NAbs in mice, which neutralised HCVcc of all the seven genotypes more potently than the monovalent vaccine. Further analyses demonstrated that each sE2 component of this trivalent vaccine elicited unique spectrum of NAbs which acted synergistically to inhibit HCV infection. Finally, the trivalent vaccine triggered stronger and more uniform multigenotypic neutralising antibody response than the monovalent vaccine in rhesus macaques.

Conclusions In summary, we developed a trivalent HCV vaccine that induces broad and synergistic-acting neutralising antibodies in mice and non-human primates.

  • hepatitis c
  • infectious disease
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Footnotes

  • XW and YY contributed equally.

  • Contributors XW and YY designed/conducted the experiments, acquired/analysed the data and wrote the manuscript. TG conducted the experiments. XY and DZ helped conduct the experiments and provided critical reagents. DL generated critical reagents. QS provided experimental support. JZ and ZH designed the study, analysed the data and wrote the manuscript.

  • Funding This work was supported by grants from National Natural Science Foundation of China (81330039), Chinese National 973 Program (2015CB554300) to JZ, CAS-SAFEA International Partnership Program for Creative Research Teams to JZ and ZH.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data described in the manuscript can be shared on request.

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