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Viruses. 2021 Nov 16;13(11). doi: 10.3390/v13112290.

Deciphering the Role of Humoral and Cellular Immune Responses in Different COVID-19 Vaccines-A Comparison of Vaccine Candidate Genes in Roborovski Dwarf Hamsters.

Viruses

Jakob Trimpert, Susanne Herwig, Julia Stein, Daria Vladimirova, Julia M Adler, Azza Abdelgawad, Theresa C Firsching, Tizia Thoma, Jalid Sehouli, Klaus Osterrieder, Achim D Gruber, Birgit Sawitzki, Leif Erik Sander, Günter Cichon

Affiliations

  1. Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany.
  2. Department of Gynecology, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, 13353 Berlin, Germany.
  3. Institute of Medical Immunology, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
  4. Institute of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany.
  5. Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.
  6. Department of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.

PMID: 34835096 PMCID: PMC8625836 DOI: 10.3390/v13112290

Abstract

With the exception of inactivated vaccines, all SARS-CoV-2 vaccines currently used for clinical application focus on the spike envelope glycoprotein as a virus-specific antigen. Compared to other SARS-CoV-2 genes, mutations in the spike protein gene are more rapidly selected and spread within the population, which carries the risk of impairing the efficacy of spike-based vaccines. It is unclear to what extent the loss of neutralizing antibody epitopes can be compensated by cellular immune responses, and whether the use of other SARS-CoV-2 antigens might cause a more diverse immune response and better long-term protection, particularly in light of the continued evolution towards new SARS-CoV-2 variants. To address this question, we explored immunogenicity and protective effects of adenoviral vectors encoding either the full-length spike protein (S), the nucleocapsid protein (N), the receptor binding domain (RBD) or a hybrid construct of RBD and the membrane protein (M) in a highly susceptible COVID-19 hamster model. All adenoviral vaccines provided life-saving protection against SARS-CoV-2-infection. The most efficient protection was achieved after exposure to full-length spike. However, the nucleocapsid protein, which triggered a robust T-cell response but did not facilitate the formation of neutralizing antibodies, controlled early virus replication efficiently and prevented severe pneumonia. Although the full-length spike protein is an excellent target for vaccines, it does not appear to be the only option for future vaccine design.

Keywords: SARS-CoV-2; adenoviral vectors; animal model; dwarf hamster; vaccine genes

References

  1. Cell Rep. 2020 Dec 8;33(10):108488 - PubMed
  2. Acta Virol. 2020;64(2):245-250 - PubMed
  3. Curr Top Microbiol Immunol. 2005;287:1-30 - PubMed
  4. Nature. 2020 May;581(7809):465-469 - PubMed
  5. Cell Mol Immunol. 2004 Jun;1(3):193-8 - PubMed
  6. Hum Cell. 2021 May;34(3):711-733 - PubMed
  7. Bing Du Xue Bao. 2015 Nov;31(6):634-40 - PubMed
  8. Am J Respir Cell Mol Biol. 2020 Dec;63(6):856-859 - PubMed
  9. Virus Res. 2020 Oct 15;288:198141 - PubMed
  10. Euro Surveill. 2020 May;25(21): - PubMed
  11. Viruses. 2020 Jul 20;12(7): - PubMed
  12. N Engl J Med. 2021 May 20;384(20):1885-1898 - PubMed
  13. J Vet Med Sci. 2017 Jul 19;79(7):1230-1235 - PubMed
  14. J Virol. 1996 Nov;70(11):7498-509 - PubMed
  15. Nat Rev Microbiol. 2021 Jul;19(7):409-424 - PubMed
  16. Nature. 2021 Apr;592(7854):438-443 - PubMed
  17. Nature. 2003 Nov 27;426(6965):450-4 - PubMed
  18. Int Immunopharmacol. 2020 Sep;86:106738 - PubMed
  19. Nat Rev Immunol. 2021 Apr;21(4):195-197 - PubMed
  20. Biology (Basel). 2021 Jan 26;10(2): - PubMed
  21. J Med Virol. 2020 May;92(5):495-500 - PubMed
  22. Virus Res. 2020 Oct 15;288:198082 - PubMed
  23. J Vet Sci. 2018 May 31;19(3):416-425 - PubMed
  24. Infect Drug Resist. 2021 Aug 31;14:3459-3476 - PubMed

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