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Protective cellular immune response against hepatitis C virus elicited by chimeric protein formulations in BALB/c mice

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Abstract

The eradication of hepatitis C virus (HCV) infection is a public health priority. Despite the efficiency of treatment with direct-acting antivirals, the high cost of the therapy and the lack of accurate data about the HCV-infected population worldwide constitute important factors hampering this task. Hence, an affordable preventive vaccine is still necessary for reducing transmission and the future disease burden globally. In this work, chimeric proteins (EnvCNS3 and NS3EnvCo) encompassing conserved and immunogenic epitopes from the HCV core, E1, E2 and NS3 proteins were produced in Escherichia coli, and their immunogenicity was evaluated in BALB/c mice. The impact of recombinant HCV E2.680 protein and oligodeoxynucleotide 39M (ODN39M) on the immune response to chimeric proteins was also assessed. Immunization with chimeric proteins mixed with E2.680 enhanced the antibody and cellular response against HCV antigens and chimeric proteins. Interestingly, the combination of NS3EnvCo with E2.680 and ODN39M as adjuvant elicited a potent antibody response characterized by an increase in antibodies of the IgG2a subclass against E2.680, NS3 and chimeric proteins, suggesting the induction of a Th1-type response. Moreover, a cytotoxic T lymphocyte response and a broad response of IFN-γ-secreting cells against HCV antigens were induced with this formulation as well. This T cell response was able to protect vaccinated mice against challenge with a surrogate model based on HCV recombinant vaccinia virus. Overall, the vaccine candidate NS3EnvCo/E2.680/ODN39M might constitute an effective immunogen against HCV with potential for reducing the likelihood of viral persistence.

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Acknowledgements

The authors would like to thank Lázaro Gil González, Alexis Musacchio Lasa, Tania Cárdenas Borrego and Ingrid Rodríguez for their valuable contribution to this work.

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Authors and Affiliations

  1. Hepatitis C virus Department, Center for Genetic Engineering and Biotechnology, Avenue 31, P.O. Box. 6162, Havana, 610600, Cuba

    Santa Olivera, Angel Perez & Gillian Martinez-Donato

  2. Microscopy Department, Center for Genetic Engineering and Biotechnology, Avenue 31, P.O. Box. 6162, Havana, 610600, Cuba

    Viviana Falcon

  3. Animal Care Facility, Center for Genetic Engineering and Biotechnology, Avenue 31, P.O. Box. 6162, Havana, 610600, Cuba

    Dioslaida Urquiza & Dagmara Pichardo

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  1. Santa Olivera
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  2. Angel Perez
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  3. Viviana Falcon
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  6. Gillian Martinez-Donato
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Correspondence to Santa Olivera.

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Olivera, S., Perez, A., Falcon, V. et al. Protective cellular immune response against hepatitis C virus elicited by chimeric protein formulations in BALB/c mice. Arch Virol 165, 593–607 (2020). https://doi.org/10.1007/s00705-019-04464-x

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  • DOI: https://doi.org/10.1007/s00705-019-04464-x