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

Anthony T. DiPiazza, Sarah R. Leist, Olubukola M. Abiona, Juan I. Moliva, Anne Werner, Mahnaz Minai, Bianca M. Nagata, Kevin W. Bock, Emily Phung, Alexandra Schäfer, Kenneth H. Dinnon, Lauren A. Chang, Rebecca J. Loomis, Seyhan Boyoglu-Barnum, Gabriela S. Alvarado, Nancy J. Sullivan, Darin K. Edwards, Kaitlyn M. Morabito, John R. Mascola, Andrea CarfiKizzmekia S. Corbett, Ian N. Moore, Ralph S. Baric, Barney S. Graham, Tracy J. Ruckwardt

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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.

Original languageEnglish
Pages (from-to)1869-1882.e6
JournalImmunity
Volume54
Issue number8
DOIs
StatePublished - 10 Aug 2021
Externally publishedYes

Keywords

  • COVID-19
  • SARS-CoV-2
  • T cells
  • mRNA vaccine
  • mRNA-1273
  • neutralizing antibodies
  • protective immunity
  • type 2 responses
  • vaccine-associated enhanced respiratory disease

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this