First Author | Seephetdee C | Year | 2022 |
Journal | bioRxiv | Mgi Jnum | J:321929 |
Mgi Id | MGI:7256390 | Doi | 10.1101/2022.03.17.484759 |
Citation | Seephetdee C, et al. (2022) Broad neutralization of SARS-CoV-2 variants bu circular mRNA producing VFLIP-X spike in mice. bioRxiv |
abstractText | Next-generation COVID-19 vaccines are critical due to the ongoing evolution of SARS-CoV-2 virus. The m RNA vaccines m RNA-1273 and 8NT162b2 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 8.1.617.2 and 8.1.1.529. Recently, a new version of spike trimers namely VFLIP has been suggested to possess native-like glycosylation, as opposed to S-2P. Here, we report that the spike protein VFLIP-X, containing six rationally substituted amino acids (K417N, L452R, T478K, E484K, N501Y and D614G), offers a promising candidate for a nextÂgeneration 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 TH 1 and T H2 responses was achieved by the immunization with VFLIP-X. Our results indicate that the VFLIP-X delivered by circRNA confers humeral and cellular immune responses, as well as neutralizing activity against broad SARS-CoV-2 variants. |