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Expression of the VP1 protein of FMDV integrated chromosomally with mutant Listeria monocytogenes strain induced both humoral and cellular immune responses

Abstract

Live vector-based vaccine is a modern approach to overcome the drawbacks of inactivated foot-and-mouth disease (FMD) vaccines such as improper inactivation during manufacture. Listeria monocytogenes (LM), an intracellular microorganism with immune-stimulatory properties, is appropriate to be utilized as a live bacterial vaccine vector. FMDV-VP1 protein has the capability to induce both cellular and humoral immune responses since it is considered the most immunogenic part of FMDV capsid and has the most of antigenic sites for viral neutralization. The codon-optimized vp1 gene was ligated to the integrative pCW702 plasmid to construct the target cassette. The antigen cassette was integrated successfully into the chromosome of mutant LM strain via homologous recombination for more stability to generate a candidate vaccine strain LM△actAplcB-vp1. Safety evaluation of recombinant LM△actAplcB-vp1 revealed it could be eliminated from the internal organs within 3 days as a safe candidate vaccine. Mice groups were immunized I.V. twice with the recombinant LM△actAplcB-vp1 at an interval of 2 weeks. Antigen-specific IgG antibodies and the level of CD4+- and CD8+-specific secreted cytokines were estimated to evaluate the immunogenicity of the candidate vaccine. The rapid onset immune response was detected, strong IgG humoral immune response within 14 days post immunization and augmented again after the booster dose. Cellular immunity data after 9 days post the prime dose indicated elevation in CD4+ and CD8+ secreted cytokine level with another elevation after the booster dose. This is the first report to explain the ability of attenuated mutant LM to be a promising live vector for FMDV vaccine.

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Acknowledgments

Thanks for the research platform provided by the Research Centre for Public Health and Preventive Medicine, West China School of Public Health, West China Teaching Hospital, Sichuan University.

Funding

This study was financially supported by the National Natural Science Foundation of China under Scientific Research Project (No. 31570924).

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Authors

Contributions

Chuan Wang, Mahdy S.E, and Xiaofang Pei designed the study, conceptualized and drafted the manuscript, designed and conducted the data collection, planned the data analysis, wrote the manuscript, and revised the manuscript; Sijing Liu, Lin Su, Xiang Zhang, and Hao-tai Chen analyzed the data collection.

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Correspondence to Chuan Wang.

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The authors declare that they have no conflict of interest.

Ethical approval

All Female C57BL/6J mice of 6–8 weeks old were purchased from the Institute of Laboratory Animals of Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital. Mice were kept under restricted hygienic conditions during the experiments at the Animal Centre of School of Public Health at Sichuan University. Mouse experiments were performed according to the guidelines of the Animal Care and Use Committee of Sichuan University.

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Mahdy, S.E., Liu, S., Su, L. et al. Expression of the VP1 protein of FMDV integrated chromosomally with mutant Listeria monocytogenes strain induced both humoral and cellular immune responses. Appl Microbiol Biotechnol 103, 1919–1929 (2019). https://doi.org/10.1007/s00253-018-09605-x

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  • DOI: https://doi.org/10.1007/s00253-018-09605-x

Keywords

  • FMD
  • Listeria
  • Vector vaccine
  • Recombinant
  • VP1