Author: Praktiknjo, Samantha D ; Wu, Haibo ; Adler, Julia M ; Bushe, Judith ; Nouailles, Geraldine ; Pennitz, Peter ; Blüthgen, Nils ; Kazmierski, Julia ; Martin Vidal, Ricardo ; Landthaler, Markus ; Kunec, Dusan ; Osterrieder, Nikolaus ; Baumgardt, Morris ; Goffinet, Christine ; Ebenig, Aileen ; Trimpert, Jakob ; Xing, Na ; Witzenrath, Martin ; Mühlebach, Michael D ; Drosten, Christian ; Wyler, Emanuel ; Cichon, Günter ; Peidli, Stefan ; Niemeyer, Daniela ; Voss, Anne ; Simmons, Szandor ; Abdelgawad, Azza ; Langenhagen, Alina ; Lange, Mona V ; Herwig, Susanne ; Goekeri, Cengiz ; Pott, Fabian ; Teixeira Alves, Luiz Gustavo ; Gruber, Achim D ; Langner, Christine

Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.

01 Jan 2022·Computational and Structural Biotechnology Journal

Synthetically recoded virus sCPD9 – A tool to accelerate SARS-CoV-2 research under biosafety level 2 conditions

Review

Author: Trimpert, Jakob ; Kunec, Dusan ; Osterrieder, Nikolaus

Research with infectious SARS-CoV-2 is complicated because it must be conducted under biosafety level 3 (BSL-3) conditions. Recently, we constructed a live attenuated SARS-CoV-2 virus by rational design through partial recoding of the SARS-CoV-2 genome and showed that the attenuated virus, designated sCPD9, was highly attenuated in preclinical animal models. The recoded sequence was designed by codon pair deoptimization and is located at the distal end of gene ORF1ab. Codon pair deoptimization involves recoding of the viral sequence with underrepresented codon pairs but without altering the amino acid sequence of the encoded proteins. Thus, parental and attenuated viruses produce exactly the same proteins. In Germany, the live attenuated SARS-CoV-2 mutant sCPD9 was recently classified as a BSL-2 pathogen based on its genetic stability and strong attenuation in preclinical animal models. Despite its high attenuation in vivo, sCPD9 grows to high titers in common cell lines, making it suitable as substitute for virulent SARS-CoV-2 in many experimental setups. Consequently, sCPD9 can ease and accelerate SARS-CoV-2 research under BSL-2 conditions, particularly in experiments requiring replicating virus, such as diagnostics and development of antiviral drugs.

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Indication	Highest Phase	Country/Location	Organization	Date
Coronavirus Infections	Preclinical	DE	Freie Universität Berlin	03 Apr 2023

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