PT  - JOURNAL ARTICLE
AU  - Chotiwat Seephetdee
AU  - Kanit Bhukhai
AU  - Nattawut Buasri
AU  - Puttipatch Leelukkanaveera
AU  - Pat Lerdwattanasombat
AU  - Suwimon Manopwisedjaroen
AU  - Nut Phueakphud
AU  - Sakonwan Kuhaudomlarp
AU  - Eduardo Olmedillas
AU  - Erica Ollmann Saphire
AU  - Arunee Thitithanyanont
AU  - Suradej Hongeng
AU  - Patompon Wongtrakoongate
TI  - Broad neutralization of SARS-CoV-2 variants by circular mRNA producing VFLIP-X spike in mice
AID  - 10.1101/2022.03.17.484759
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.17.484759
4099  - http://biorxiv.org/content/early/2022/03/28/2022.03.17.484759.short
4100  - http://biorxiv.org/content/early/2022/03/28/2022.03.17.484759.full
AB  - Next-generation COVID-19 vaccines are critical due to the ongoing evolution of SARS-CoV-2 virus and waning duration of the neutralizing antibody response against current vaccines. The mRNA vaccines mRNA-1273 and BNT162b2 were developed using linear transcripts encoding the prefusion-stabilized trimers (S-2P) of the wildtype spike, which have shown a reduced neutralizing activity against the variants of concern B.1.617.2 and B.1.1.529. Recently, a new version of spike trimer, termed VFLIP has been suggested to possess native-like glycosylation, and greater pre-fusion trimeric stability as opposed to S-2P. Here, we report that the spike protein VFLIP-X, containing six rationally substituted amino acids to reflect emerging variants (K417N, L452R, T478K, E484K, N501Y and D614G), offers a promising candidate for a next-generation SARS-CoV-2 vaccine. Mice immunized by a circular mRNA (circRNA) vaccine prototype producing VFLIP-X elicited neutralizing antibodies for up to 7 weeks post-boost against SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs). In addition, a balance in TH1 and TH2 responses was achieved by immunization with VFLIP-X. Our results indicate that the VFLIP-X delivered by circRNA confers humoral and cellular immune responses, as well as neutralizing activity against broad SARS-CoV-2 variants.Competing Interest StatementThe authors have declared no competing interest.