Journal Article

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

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

2024

Overview

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. Here, Dillard and Taft-Benz et al. show in a female mouse model how different adjuvants affect inactivated vaccine-mediated protection against homologous SARS-CoV-2 and heterologous SARS-CoV-1-like coronaviruses. They find that an aluminum hydroxide-adjuvanted vaccine can increase risk of adverse outcomes during heterologous infection.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/106 / 13/21 / 13/51 / 14/63 / 38 / 38/39 / 38/77 / 38/88 / 49/90 / 49/91 / 631/250/590/1883 / 631/250/590/2291 / 631/326/596/2078 / 631/326/596/4130 / 64 / 64/60 / Adjuvants / Adjuvants, Immunologic - administration & dosage / Adjuvants, Vaccine / Aluminum / Aluminum hydroxide / Aluminum Hydroxide - administration & dosage / Animals / Antibodies, Viral - immunology / Coronaviridae / Coronaviruses / COVID-19 / COVID-19 - immunology / COVID-19 - prevention & control / COVID-19 - virology / COVID-19 Vaccines - administration & dosage / COVID-19 Vaccines - immunology / Deactivation / Disease Models, Animal / Female / Females / Homology / Humanities and Social Sciences / Humans / Infections / Mice / Mice, Inbred BALB C / multidisciplinary / Pandemics / Respiratory diseases / SARS-CoV-2 - immunology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Severe acute respiratory syndrome-related coronavirus - immunology / Vaccines / Vaccines, Inactivated - immunology / Viral diseases