COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge
| Autor: | Andrea Carfi, John R. Mascola, Nancy J. Sullivan, Barney S. Graham, Kizzmekia S. Corbett, Mahnaz Minai, Olubukola M. Abiona, Tracy J. Ruckwardt, Anne P. Werner, Gabriela S. Alvarado, Ralph S. Baric, Anthony T. DiPiazza, Ian N. Moore, Lauren A. Chang, Darin K. Edwards, Emily Phung, Juan I. Moliva, Sarah R. Leist, Kenneth H. Dinnon, Seyhan Boyoglu-Barnum, Bianca M. Nagata, Rebecca J. Loomis, Kaitlyn M. Morabito, Alexandra Schäfer, Kevin W. Bock |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
COVID-19 Vaccines
Middle East respiratory syndrome coronavirus Biopsy Immunology T cells Lung injury medicine.disease_cause Antibodies Viral Virus Article mRNA-1273 protective immunity type 2 responses Mice Immune system T-Lymphocyte Subsets Immunopathology Outcome Assessment Health Care medicine Immunology and Allergy Animals Humans neutralizing antibodies RNA Messenger Vaccines Synthetic biology vaccine-associated enhanced respiratory disease SARS-CoV-2 COVID-19 Antibodies Neutralizing Immunohistochemistry Vaccination Disease Models Animal Infectious Diseases mRNA vaccine Viral replication Immunoglobulin G Host-Pathogen Interactions Spike Glycoprotein Coronavirus biology.protein Antibody |
| Zdroj: | Immunity |
| ISSN: | 1097-4180 1074-7613 |
| Popis: | Vaccine-associated enhanced respiratory disease (VAERD) was previously observed in some preclinical models of severe acute respiratory syndrome (SARS) and MERS coronavirus vaccines. We used the SARS coronavirus 2 (SARS-CoV-2) mouse-adapted, passage 10, lethal challenge virus (MA10) mouse model of acute lung injury to evaluate the immune response and potential for immunopathology in animals vaccinated with research-grade mRNA-1273. Whole-inactivated virus or heat-denatured spike protein subunit vaccines with alum designed to elicit low-potency antibodies and Th2-skewed CD4+ T cells resulted in reduced viral titers and weight loss post challenge but more severe pathological changes in the lung compared to saline-immunized animals. In contrast, a protective dose of mRNA-1273 induced favorable humoral and cellular immune responses that protected from viral replication in the upper and lower respiratory tract upon challenge. A subprotective dose of mRNA-1273 reduced viral replication and limited histopathological manifestations compared to animals given saline. Overall, our findings demonstrate an immunological signature associated with antiviral protection without disease enhancement following vaccination with mRNA-1273. Graphical abstract As vaccine-enhanced disease to respiratory viruses has been previously observed, a thorough safety evaluation of COVID-19 vaccines in preclinical animal models is essential. Here, DiPiazza and Leist et al. provide evidence for antiviral protection in the absence of lung disease following SARS-CoV-2 challenge in mice immunized with research-grade mRNA-1273. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|