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.
Immunity
; 54(8): 1869-1882.e6, 2021 08 10.
Article
en En
| MEDLINE
| ID: mdl-34270939
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Vacunas Sintéticas
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Interacciones Huésped-Patógeno
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Vacunas contra la COVID-19
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SARS-CoV-2
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COVID-19
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article