A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate.

Sanchez-Felipe, Lorena; Vercruysse, Thomas; Sharma, Sapna; Ma, Ji; Lemmens, Viktor; Van Looveren, Dominique; Javarappa, Mahadesh Prasad Arkalagud; Boudewijns, Robbert; Malengier-Devlies, Bert; Liesenborghs, Laurens; Kaptein, Suzanne J F; De Keyzer, Carolien; Bervoets, Lindsey; Debaveye, Sarah; Rasulova, Madina; Seldeslachts, Laura; Li, Li-Hsin; Jansen, Sander; Yakass, Michael Bright; Verstrepen, Babs E; Böszörményi, Kinga P; Kiemenyi-Kayere, Gwendoline; van Driel, Nikki; Quaye, Osbourne; Zhang, Xin; Ter Horst, Sebastiaan; Mishra, Niraj; Deboutte, Ward; Matthijnssens, Jelle; Coelmont, Lotte; Vandermeulen, Corinne; Heylen, Elisabeth; Vergote, Valentijn; Schols, Dominique; Wang, Zhongde; Bogers, Willy; Kuiken, Thijs; Verschoor, Ernst; Cawthorne, Christopher; Van Laere, Koen; Opdenakker, Ghislain; Velde, Greetje Vande; Weynand, Birgit; Teuwen, Dirk E; Matthys, Patrick; Neyts, Johan; Jan Thibaut, Hendrik; Dallmeier, Kai

The explosively expanding COVID-19 pandemic urges the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are leveraged for a rapid emergency response1. We describe the discovery of a live virus-vectored SARS-CoV-2 vaccine candidate using the yellow fever 17D (YF17D) vaccine as vector to express a non-cleavable prefusion form of the SARS-CoV-2 Spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. Vaccine candidate YF-S0 has an outstanding safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters, mice and cynomolgus macaques and concomitantly a protective immunity against YFV. Humoral immunity is complemented by a favourable Th1 cell-mediated immune response as profiled in mice. In a stringent hamster model2 as well as in non-human primates, YF-S0 prevents infection with SARS-CoV-2. Moreover, in hamsters, a single dose confers protection from lung disease in most vaccinated animals within 10 days. Taken together, the quality of immune responses triggered and the rapid kinetics by which protective immunity can be mounted already after a single dose warrant further development this potent SARS-CoV-2 vaccine candidate.