RT Journal Article
SR Electronic
T1 Design and immunogenicity of a Pan-SARS-CoV-2 synthetic DNA vaccine
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.11.443592
DO 10.1101/2021.05.11.443592
A1 Charles C. Reed
A1 Katherine Schultheis
A1 Viviane M. Andrade
A1 Richa Kalia
A1 Jared Tur
A1 Blake Schouest
A1 Dustin Elwood
A1 Jewell N. Walters
A1 Igor Maricic
A1 Arthur Doan
A1 Miguel Vazquez
A1 Zeena Eblimit
A1 Patrick Pezzoli
A1 Dinah Amante
A1 Maria Yang
A1 Joseph Fader
A1 Roi Ferrer
A1 David B. Weiner
A1 J. Joseph Kim
A1 Laurent M. Humeau
A1 Stephanie J. Ramos
A1 Trevor R.F. Smith
A1 Kate E. Broderick
YR 2021
UL http://biorxiv.org/content/early/2021/05/11/2021.05.11.443592.abstract
AB First generation COVID-19 vaccines matched to the original Wuhan-Hu-1 (WT) strain are showing reduced efficacy against emerging SARS-CoV-2 variants of concern (VOC). In response, next generation vaccines either matched to a single variant or designed to provide broader coverage across the VOC group are being developed. The latter pan-SARS-CoV-2 approach may offer substantial advantages in terms of cross-strain protection, immune coverage, reduced susceptibility to escape mutants, and non-restricted geographical use. Here we have employed our SynCon® design technology to construct a DNA vaccine expressing a pan-Spike immunogen (INO-4802) to induce broad immunity across SARS-CoV-2 variants. Compared to WT and VOC-matched vaccines which showed limited cross-neutralizing activity, INO-4802 induced potent neutralizing antibodies and T cell responses against WT as well as B.1.1.7, P.1, and B.1.351 VOCs in a murine model. In addition, a hamster vaccination model showed enhanced humoral responses against VOCs in a heterologous pWT prime/INO-4802 boost setting. These results demonstrate the potential of the pan-SARS-CoV-2 vaccine, INO-4802 to induce cross-reactive immune responses against emerging VOCs as either a standalone vaccine, or as a potential boost for individuals previously immunized with WT-matched vaccines.Competing Interest StatementC.C.R., V.M.A., R.K., K.S., J.T., B.S., D.E., J.W., I.M., A.D., Z.E., P.P., D.A. M.Y., J.F., R.F., M.V., J.J.K., L.M.H., S.J.R., T.R.F.S., K.E.B. are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options, from the company. D.B.W. has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees and board services. Remuneration received by D.B.W. includes direct payments or stock or stock options, and in the interest of disclosure he notes potential conflicts associated with this work with Inovio and possibly others. In addition, he has a patent DNA vaccine delivery pending to Inovio. All other authors report there are no competing interests.