Deciphering the Role of Humoral and Cellular Immune Responses in Different COVID-19 Vaccines—A Comparison of Vaccine Candidate Genes in Roborovski Dwarf Hamsters
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
Jakob Trimpert
Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany
Susanne Herwig
Department of Gynecology, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, 13353 Berlin, Germany
Julia Stein
Institute of Medical Immunology, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany
Daria Vladimirova
Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany
Julia M. Adler
Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany
Azza Abdelgawad
Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany
Theresa C. Firsching
Institute of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany
Tizia Thoma
Institute of Medical Immunology, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany
Jalid Sehouli
Department of Gynecology, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, 13353 Berlin, Germany
Klaus Osterrieder
Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong
Achim D. Gruber
Institute of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany
Birgit Sawitzki
Institute of Medical Immunology, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany
Leif Erik Sander
Department of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany
Günter Cichon
Department of Gynecology, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, 13353 Berlin, Germany
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.
