A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine

Jangra, S.; Landers, J. J.; Rathnasinghe, R.; O'Konek, J. J.; Janczak, K. W.; Cascalho, M.; Kennedy, A. A.; Tai, A. W.; Baker, J. R.; Schotsaert, M.; Wong, P. T.

doi:10.1101/2021.02.18.431484

bioRxiv · 10.1101/2021.02.18.431484

A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine

Jangra, S.·Landers, J. J.·Rathnasinghe, R.·O'Konek, J. J.·Janczak, K. W.·Cascalho, M.·Kennedy, A. A.·Tai, A. W.·Baker, J. R.·Schotsaert, M.·Wong, P. T.

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Abstract

Several SARS-CoV-2 vaccines have received EUAs, but many issues remain unresolved, including duration of conferred immunity and breadth of cross-protection. Adjuvants that enhance and shape adaptive immune responses that confer broad protection against SARS-CoV-2 variants will be pivotal for long-term protection. We developed an intranasal, rationally designed adjuvant integrating a nanoemulsion (NE) that activates TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI). The combination adjuvant with spike protein antigen elicited robust responses to SARS-CoV-2 in mice, with markedly enhanced TH1-biased cellular responses and high virus-neutralizing antibody titers towards both homologous SARS-CoV-2 and a variant harboring the N501Y mutation shared by B1.1.7, B.1.351 and P.1 variants. Furthermore, passive transfer of vaccination-induced antibodies protected naive mice against heterologous viral challenge. NE/IVT DI enables mucosal vaccination, and has the potential to improve the immune profile of a variety of SARS-CoV-2 vaccine candidates to provide effective cross-protection against future drift variants.

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Jangra, S., Landers, J. J., Rathnasinghe, R., O'Konek, J. J., Janczak, K. W., Cascalho, M., Kennedy, A. A., Tai, A. W., Baker, J. R., Schotsaert, M., Wong, P. T.. 2021-02-18. A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine. https://doi.org/10.1101/2021.02.18.431484

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