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

• Published in: Frontiers in immunology Vol. 12; p. 729189
• Main Authors: Jangra, Sonia, Landers, Jeffrey J., Rathnasinghe, Raveen, O’Konek, Jessica J., Janczak, Katarzyna W., Cascalho, Marilia, Kennedy, Andrew A., Tai, Andrew W., Baker, James R., Schotsaert, Michael, Wong, Pamela T.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 16.09.2021
• Subjects: Adaptive Immunity - immunology; Adjuvants, Immunologic - pharmacology; Animals; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Chlorocebus aethiops; COVID-19 - prevention & control; COVID-19 Vaccines - immunology; Cross Protection - immunology; cross-protection; DEAD Box Protein 58; HEK293 Cells; Humans; Immunity, Humoral - immunology; Immunization, Passive; Immunology; intranasal vaccine; Mice; Mice, Inbred C57BL; mucosal adjuvant; nanoemulsion (NE); Receptors, Immunologic - agonists; Recombinant Proteins - immunology; RIG-I agonist; SARS-CoV-2; SARS-CoV-2 - immunology; Spike Glycoprotein, Coronavirus - immunology; Vaccination; Vaccines, Synthetic - immunology; Vero Cells; intranasal vaccine; nanoemulsion (NE); SARS-CoV-2; mucosal adjuvant; RIG-I agonist; cross-protection
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.729189

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 as drift variants continue to emerge. 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 T H 1-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.