RT Journal Article
SR Electronic
T1 mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.25.428136
DO 10.1101/2021.01.25.428136
A1 Michelle Meyer
A1 Yuan Wang
A1 Darin Edwards
A1 Gregory R. Smith
A1 Aliza B. Rubenstein
A1 Palaniappan Ramanathan
A1 Chad E. Mire
A1 Colette Pietzsch
A1 Xi Chen
A1 Yongchao Ge
A1 Wan Sze Cheng
A1 Carole Henry
A1 Angela Woods
A1 LingZhi Ma
A1 Guillaume B. E. Stewart-Jones
A1 Kevin W. Bock
A1 Mahnaz Minai
A1 Bianca M. Nagata
A1 Sivakumar Periasamy
A1 Pei-Yong Shi
A1 Barney S. Graham
A1 Ian N. Moore
A1 Irene Ramos
A1 Olga G. Troyanskaya
A1 Elena Zaslavsky
A1 Andrea Carfi
A1 Stuart C. Sealfon
A1 Alexander Bukreyev
YR 2021
UL http://biorxiv.org/content/early/2021/01/25/2021.01.25.428136.abstract
AB The mRNA-1273 vaccine was recently determined to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from interim Phase 3 results. Human studies, however, cannot provide the controlled response to infection and complex immunological insight that are only possible with preclinical studies. Hamsters are the only model that reliably exhibit more severe SARS-CoV-2 disease similar to hospitalized patients, making them pertinent for vaccine evaluation. We demonstrate that prime or prime-boost administration of mRNA-1273 in hamsters elicited robust neutralizing antibodies, ameliorated weight loss, suppressed SARS-CoV-2 replication in the airways, and better protected against disease at the highest prime-boost dose. Unlike in mice and non-human primates, mRNA-1273- mediated immunity was non-sterilizing and coincided with an anamnestic response. Single-cell RNA sequencing of lung tissue permitted high resolution analysis which is not possible in vaccinated humans. mRNA-1273 prevented inflammatory cell infiltration and the reduction of lymphocyte proportions, but enabled antiviral responses conducive to lung homeostasis. Surprisingly, infection triggered transcriptome programs in some types of immune cells from vaccinated hamsters that were shared, albeit attenuated, with mock-vaccinated hamsters. Our results support the use of mRNA-1273 in a two-dose schedule and provides insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.Competing Interest StatementD.E., C.H., A.W., L.M, G.S-J. and A.C. are employees of Moderna, Inc. The other authors declare