A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine
Copyright policy )A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine
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 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.
- Duke University United States
- University of Michigan–Flint United States
- VA Ann Arbor Healthcare System United States
- Department of Microbiology United States
- Icahn School of Medicine at Mount Sinai United States
cross-protection, COVID-19 Vaccines, Cross Protection, Immunology, nanoemulsion (NE), Adaptive Immunity, Antibodies, Viral, Mice, Adjuvants, Immunologic, intranasal vaccine, Chlorocebus aethiops, Animals, Humans, Receptors, Immunologic, SARS-CoV-2, RIG-I agonist, Immunization, Passive, COVID-19, mucosal adjuvant, RC581-607, Antibodies, Neutralizing, Recombinant Proteins, Immunity, Humoral, Mice, Inbred C57BL, HEK293 Cells, Spike Glycoprotein, Coronavirus, DEAD Box Protein 58, Immunologic diseases. Allergy
cross-protection, COVID-19 Vaccines, Cross Protection, Immunology, nanoemulsion (NE), Adaptive Immunity, Antibodies, Viral, Mice, Adjuvants, Immunologic, intranasal vaccine, Chlorocebus aethiops, Animals, Humans, Receptors, Immunologic, SARS-CoV-2, RIG-I agonist, Immunization, Passive, COVID-19, mucosal adjuvant, RC581-607, Antibodies, Neutralizing, Recombinant Proteins, Immunity, Humoral, Mice, Inbred C57BL, HEK293 Cells, Spike Glycoprotein, Coronavirus, DEAD Box Protein 58, Immunologic diseases. Allergy
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