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. 2021 Nov 16;13(11):2290. doi: 10.3390/v13112290.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Antigens, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • COVID-19 / prevention & control
  • COVID-19 / virology
  • COVID-19 Vaccines / immunology*
  • Coronavirus Nucleocapsid Proteins / genetics
  • Coronavirus Nucleocapsid Proteins / immunology
  • Cricetinae
  • Female
  • Immunity, Cellular*
  • Immunity, Humoral*
  • Immunogenicity, Vaccine*
  • Inflammation
  • Lung / pathology
  • Lung / virology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / physiology
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • COVID-19 Vaccines
  • Coronavirus Nucleocapsid Proteins
  • Phosphoproteins
  • Spike Glycoprotein, Coronavirus
  • Viral Matrix Proteins
  • membrane protein, SARS-CoV-2
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2