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Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection
Molecular Therapy ( IF 12.1 ) Pub Date : 2021-10-20 , DOI: 10.1016/j.ymthe.2021.10.008
Stephen Boulton 1 , Joanna Poutou 1 , Nikolas T Martin 1 , Taha Azad 1 , Ragunath Singaravelu 1 , Mathieu J F Crupi 1 , Taylor Jamieson 1 , Xiaohong He 1 , Ricardo Marius 1 , Julia Petryk 1 , Christiano Tanese de Souza 1 , Bradley Austin 1 , Zaid Taha 1 , Jack Whelan 1 , Sarwat T Khan 2 , Adrian Pelin 1 , Reza Rezaei 1 , Abera Surendran 1 , Sarah Tucker 1 , Emily E F Fekete 1 , Jaahnavi Dave 1 , Jean-Simon Diallo 1 , Rebecca Auer 1 , Jonathan B Angel 3 , D William Cameron 4 , Jean-Francois Cailhier 5 , Réjean Lapointe 5 , Kyle Potts 6 , Douglas J Mahoney 6 , John C Bell 1 , Carolina S Ilkow 1
Affiliation  

The coronavirus disease 2019 (COVID-19) pandemic requires the continued development of safe, long-lasting, and efficacious vaccines for preventive responses to major outbreaks around the world, and especially in isolated and developing countries. To combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we characterize a temperature-stable vaccine candidate (TOH-Vac1) that uses a replication-competent, attenuated vaccinia virus as a vector to express a membrane-tethered spike receptor binding domain (RBD) antigen. We evaluate the effects of dose escalation and administration routes on vaccine safety, efficacy, and immunogenicity in animal models. Our vaccine induces high levels of SARS-CoV-2 neutralizing antibodies and favorable T cell responses, while maintaining an optimal safety profile in mice and cynomolgus macaques. We demonstrate robust immune responses and protective immunity against SARS-CoV-2 variants after only a single dose. Together, these findings support further development of our novel and versatile vaccine platform as an alternative or complementary approach to current vaccines.

更新日期:2021-10-20
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