Adjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus

Jacob A. Dillard, Sharon A. Taft-Benz, Audrey C. Knight, Elizabeth J. Anderson, Katia D. Pressey, Breantié Parotti, Sabian A. Martinez, Jennifer L. Diaz, Sanjay Sarkar, Emily A. Madden, Gabriela De la Cruz, Lily E. Adams, Kenneth H. Dinnon, Sarah R. Leist, David R. Martinez, Alexandra Schäfer, John M. Powers, Boyd L. Yount, Izabella N. Castillo, Noah L. Morales, Jane Burdick, Mia Katrina D. Evangelista, Lauren M. Ralph, Nicholas C. Pankow, Colton L. Linnertz, Premkumar Lakshmanane, Stephanie A. Montgomery, Martin T. Ferris, Ralph S. Baric, Victoria K. Baxter () and Mark T. Heise ()
Additional contact information
Jacob A. Dillard: University of North Carolina at Chapel Hill
Sharon A. Taft-Benz: University of North Carolina at Chapel Hill
Audrey C. Knight: University of North Carolina at Chapel Hill
Elizabeth J. Anderson: University of North Carolina at Chapel Hill
Katia D. Pressey: University of North Carolina at Chapel Hill
Breantié Parotti: University of North Carolina at Chapel Hill
Sabian A. Martinez: University of North Carolina at Chapel Hill
Jennifer L. Diaz: University of North Carolina at Chapel Hill
Sanjay Sarkar: University of North Carolina at Chapel Hill
Emily A. Madden: University of North Carolina at Chapel Hill
Gabriela De la Cruz: University of North Carolina at Chapel Hill
Lily E. Adams: University of North Carolina at Chapel Hill
Kenneth H. Dinnon: University of North Carolina at Chapel Hill
Sarah R. Leist: University of North Carolina at Chapel Hill
David R. Martinez: University of North Carolina at Chapel Hill
Alexandra Schäfer: University of North Carolina at Chapel Hill
John M. Powers: University of North Carolina at Chapel Hill
Boyd L. Yount: University of North Carolina at Chapel Hill
Izabella N. Castillo: University of North Carolina at Chapel Hill
Noah L. Morales: University of North Carolina at Chapel Hill
Jane Burdick: University of North Carolina at Chapel Hill
Mia Katrina D. Evangelista: University of North Carolina at Chapel Hill
Lauren M. Ralph: University of North Carolina at Chapel Hill
Nicholas C. Pankow: University of North Carolina at Chapel Hill
Colton L. Linnertz: University of North Carolina at Chapel Hill
Premkumar Lakshmanane: University of North Carolina at Chapel Hill
Stephanie A. Montgomery: University of North Carolina at Chapel Hill
Martin T. Ferris: University of North Carolina at Chapel Hill
Ralph S. Baric: University of North Carolina at Chapel Hill
Victoria K. Baxter: University of North Carolina at Chapel Hill
Mark T. Heise: University of North Carolina at Chapel Hill

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat. We show that inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide can cause enhanced respiratory disease during heterologous infection, while use of an alternative adjuvant does not drive disease and promotes heterologous viral clearance. In this work, we highlight the impact of adjuvant selection on inactivated vaccine safety and efficacy against heterologous coronavirus infection.

Date: 2024
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DOI: 10.1038/s41467-024-47450-x

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