Insights from the Construction of Adenovirus-Based Vaccine Candidates against SARS-CoV-2: Expecting the Unexpected
Denice Weklak,
Julian Tisborn,
Maurin Helen Mangold,
Raphael Scheu,
Harald Wodrich,
Claudia Hagedorn,
Franziska Jönsson,
Florian Kreppel
Affiliations
Denice Weklak
Chair of Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Stockumer Str. 10, 58453 Witten, Germany
Julian Tisborn
Chair of Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Stockumer Str. 10, 58453 Witten, Germany
Maurin Helen Mangold
Chair of Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Stockumer Str. 10, 58453 Witten, Germany
Raphael Scheu
Chair of Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Stockumer Str. 10, 58453 Witten, Germany
Harald Wodrich
Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, 33076 Bordeaux, France
Claudia Hagedorn
Chair of Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Stockumer Str. 10, 58453 Witten, Germany
Franziska Jönsson
Chair of Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Stockumer Str. 10, 58453 Witten, Germany
Florian Kreppel
Chair of Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Stockumer Str. 10, 58453 Witten, Germany
To contain the spread of the SARS-CoV-2 pandemic, rapid development of vaccines was required in 2020. Rational design, international efforts, and a lot of hard work yielded the market approval of novel SARS-CoV-2 vaccines based on diverse platforms such as mRNA or adenovirus vectors. The great success of these technologies, in fact, contributed significantly to control the pandemic. Consequently, most scientific literature available in the public domain discloses the results of clinical trials and reveals data of efficaciousness. However, a description of processes and rationales that led to specific vaccine design is only partially available, in particular for adenovirus vectors, even though it could prove helpful for future developments. Here, we disclose our insights from the endeavors to design compatible functional adenoviral vector platform expression cassettes for the SARS-CoV-2 spike protein. We observed that contextualizing genes from an ssRNA virus into a DNA virus provides significant challenges. Besides affecting physical titers, expression cassette design of adenoviral vaccine candidates can affect viral propagation and spike protein expression. Splicing of mRNAs was affected, and fusogenicity of the spike protein in ACE2-overexpressing cells was enhanced when the ER retention signal was deleted.
