PLoS ONE (Jan 2021)

Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters.

  • Rakesh Kulkarni,
  • Wen-Ching Chen,
  • Ying Lee,
  • Chi-Fei Kao,
  • Shiu-Lok Hu,
  • Hsiu-Hua Ma,
  • Jia-Tsrong Jan,
  • Chun-Che Liao,
  • Jian-Jong Liang,
  • Hui-Ying Ko,
  • Cheng-Pu Sun,
  • Yin-Shoiou Lin,
  • Yu-Chiuan Wang,
  • Sung-Chan Wei,
  • Yi-Ling Lin,
  • Che Ma,
  • Yu-Chan Chao,
  • Yu-Chi Chou,
  • Wen Chang

DOI
https://doi.org/10.1371/journal.pone.0257191
Journal volume & issue
Vol. 16, no. 9
p. e0257191

Abstract

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COVID-19 in humans is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that belongs to the beta family of coronaviruses. SARS-CoV-2 causes severe respiratory illness in 10-15% of infected individuals and mortality in 2-3%. Vaccines are urgently needed to prevent infection and to contain viral spread. Although several mRNA- and adenovirus-based vaccines are highly effective, their dependence on the "cold chain" transportation makes global vaccination a difficult task. In this context, a stable lyophilized vaccine may present certain advantages. Accordingly, establishing additional vaccine platforms remains vital to tackle SARS-CoV-2 and any future variants that may arise. Vaccinia virus (VACV) has been used to eradicate smallpox disease, and several attenuated viral strains with enhanced safety for human applications have been developed. We have generated two candidate SARS-CoV-2 vaccines based on two vaccinia viral strains, MVA and v-NY, that express full-length SARS-CoV-2 spike protein. Whereas MVA is growth-restricted in mammalian cells, the v-NY strain is replication-competent. We demonstrate that both candidate recombinant vaccines induce high titers of neutralizing antibodies in C57BL/6 mice vaccinated according to prime-boost regimens. Furthermore, our vaccination regimens generated TH1-biased immune responses in mice. Most importantly, prime-boost vaccination of a Syrian hamster infection model with MVA-S and v-NY-S protected the hamsters against SARS-CoV-2 infection, supporting that these two vaccines are promising candidates for future development. Finally, our vaccination regimens generated neutralizing antibodies that partially cross-neutralized SARS-CoV-2 variants of concern.