Frontiers in Immunology (Sep 2021)
A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine
- Sonia Jangra,
- Sonia Jangra,
- Jeffrey J. Landers,
- Jeffrey J. Landers,
- Jeffrey J. Landers,
- Raveen Rathnasinghe,
- Raveen Rathnasinghe,
- Raveen Rathnasinghe,
- Jessica J. O’Konek,
- Jessica J. O’Konek,
- Jessica J. O’Konek,
- Katarzyna W. Janczak,
- Katarzyna W. Janczak,
- Katarzyna W. Janczak,
- Marilia Cascalho,
- Marilia Cascalho,
- Andrew A. Kennedy,
- Andrew W. Tai,
- Andrew W. Tai,
- Andrew W. Tai,
- James R. Baker,
- James R. Baker,
- James R. Baker,
- Michael Schotsaert,
- Michael Schotsaert,
- Pamela T. Wong,
- Pamela T. Wong,
- Pamela T. Wong
Affiliations
- Sonia Jangra
- Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, United States
- Sonia Jangra
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Jeffrey J. Landers
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
- Jeffrey J. Landers
- Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, United States
- Jeffrey J. Landers
- Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, United States
- Raveen Rathnasinghe
- Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, United States
- Raveen Rathnasinghe
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Raveen Rathnasinghe
- Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Jessica J. O’Konek
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
- Jessica J. O’Konek
- Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, United States
- Jessica J. O’Konek
- Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, United States
- Katarzyna W. Janczak
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
- Katarzyna W. Janczak
- Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, United States
- Katarzyna W. Janczak
- Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, United States
- Marilia Cascalho
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, United States
- Marilia Cascalho
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, United States
- Andrew A. Kennedy
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
- Andrew W. Tai
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
- Andrew W. Tai
- Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, United States
- Andrew W. Tai
- Medicine Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, United States
- James R. Baker
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
- James R. Baker
- Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, United States
- James R. Baker
- Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, United States
- Michael Schotsaert
- Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, NY, United States
- Michael Schotsaert
- Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Pamela T. Wong
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
- Pamela T. Wong
- Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, Ann Arbor, MI, United States
- Pamela T. Wong
- Mary H. Weiser Food Allergy Center, University of Michigan Medical School, Ann Arbor, MI, United States
- DOI
- https://doi.org/10.3389/fimmu.2021.729189
- Journal volume & issue
-
Vol. 12
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 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.
Keywords