A universal SARS‐CoV DNA vaccine inducing highly cross‐reactive neutralizing antibodies and T cells
Sofia Appelberg, Gustaf Ahlén, Jingyi Yan, Negin Nikouyan, Sofie Weber, Olivia Larsson, Urban Höglund, Soo Aleman, Friedemann Weber, Emma Perlhamre, Johanna Apro, Eva‐Karin Gidlund, Ola Tuvesson, Simona Salati, Matteo Cadossi, Hanna Tegel, Sophia Hober, Lars Frelin, Alì Mirazimi, Matti Sällberg
Abstract
New variants in the SARS‐CoV‐2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS‐CoV‐2 DNA vaccine containing receptor‐binding domain loops from the huCoV‐19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies crossreactive between huCoV‐19/WH01, Beta, and Delta spike proteins that neutralized huCoV‐19/WH01, Beta, Delta, and Omicron virus in vitro. The vaccine primed nucleoprotein‐specific T cells, unlike spike‐specific T cells, recognized Bat‐CoV sequences. The vaccine protected mice carrying the human ACE2 receptor against lethal infection with the SARS‐CoV‐2 Beta variant. Interestingly, priming of cross‐reactive nucleoprotein‐specific T cells alone was 60% protective, verifying observations from humans that T cells protect against lethal disease. This SARS‐CoV vaccine induces a uniquely broad and functional immunity that adds to currently used vaccines. This work describes the design and evaluation of a new type of genetic COVID‐19 vaccine, containing three binding domains from three SARS‐CoV‐2 variants combined with the M and the N proteins. This work describes the design and evaluation of a new type of genetic COVID‐19 vaccine, containing three binding domains from three SARS‐CoV‐2 variants combined with the M and the N proteins.