Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

Geraldine Nouailles(Humboldt-Universität zu Berlin), Julia M. Adler(Humboldt-Universität zu Berlin), Peter Pennitz(Humboldt-Universität zu Berlin), Stefan Peidli(Humboldt-Universität zu Berlin), Luiz Gustavo Teixeira Alves(Max Delbrück Center), Morris Baumgardt(Humboldt-Universität zu Berlin), Judith Bushe(Freie Universität Berlin), Anne Voß(Freie Universität Berlin), Alina Langenhagen(Freie Universität Berlin), Christine Langner(Freie Universität Berlin), Ricardo Martin Vidal(Freie Universität Berlin), Fabian Pott(Humboldt-Universität zu Berlin), Julia Kazmierski(Humboldt-Universität zu Berlin), Aileen Ebenig(Paul Ehrlich Institut), Mona V. Lange(Paul Ehrlich Institut), Michael D. Mühlebach(German Center for Infection Research), Cengiz Goekeri(Cyprus International University), Szandor Simmons(Humboldt-Universität zu Berlin), Na Xing(Freie Universität Berlin), Azza Abdelgawad(Freie Universität Berlin), Susanne Herwig(Humboldt-Universität zu Berlin), Günter Cichon(Humboldt-Universität zu Berlin), Daniela Niemeyer(Humboldt-Universität zu Berlin), Christian Drosten(Humboldt-Universität zu Berlin), Christine Goffinet(Humboldt-Universität zu Berlin), Markus Landthaler(Max Delbrück Center), Nils Blüthgen(Humboldt-Universität zu Berlin), Haibo Wu(Chongqing University), Martin Witzenrath(Humboldt-Universität zu Berlin), Achim D. Gruber(Freie Universität Berlin), Samantha D. Praktiknjo(Berlin Institute of Health at Charité - Universitätsmedizin Berlin), Nikolaus Osterrieder(City University of Hong Kong), Emanuel Wyler(Max Delbrück Center), Dušan Kunec(Freie Universität Berlin), Jakob Trimpert(Freie Universität Berlin)
Nature Microbiology
April 3, 2023
10.1038/s41564-023-01352-8
Cited by 79Open Access
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Abstract

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.

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