RT Journal Article
SR Electronic
T1 Broad neutralization of SARS-CoV-2 variants by circular mRNA producing VFLIP-X spike in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.17.484759
DO 10.1101/2022.03.17.484759
A1 Chotiwat Seephetdee
A1 Kanit Bhukhai
A1 Nattawut Buasri
A1 Puttipatch Leelukkanaveera
A1 Pat Lerdwattanasombat
A1 Suwimon Manopwisedjaroen
A1 Nut Phueakphud
A1 Sakonwan Kuhaudomlarp
A1 Eduardo Olmedillas
A1 Erica Ollmann Saphire
A1 Arunee Thitithanyanont
A1 Suradej Hongeng
A1 Patompon Wongtrakoongate
YR 2022
UL http://biorxiv.org/content/early/2022/03/28/2022.03.17.484759.abstract
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.