TY - JOUR
T1 - Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains
AU - Ying, Baoling
AU - Whitener, Bradley
AU - VanBlargan, Laura A.
AU - Hassan, Ahmed O.
AU - Shrihari, Swathi
AU - Liang, Chieh Yu
AU - Karl, Courtney E.
AU - Mackin, Samantha
AU - Chen, Rita E.
AU - Kafai, Natasha M.
AU - Wilks, Samuel H.
AU - Smith, Derek J.
AU - Carreño, Juan Manuel
AU - Singh, Gagandeep
AU - Krammer, Florian
AU - Carfi, Andrea
AU - Elbashir, Sayda M.
AU - Edwards, Darin K.
AU - Thackray, Larissa B.
AU - Diamond, Michael
N1 - Funding Information:
We thank M. DeGrace for help in study design and funding support; R. Webby, M. Suthar, and P.-Y. Shi for viruses used in this study; K. Valentine and S. Shresta for providing immunodominant T cell peptides; B. Mühlemann for help with antigenic cartography; and E. Winkler and O. Dmytrenko for lung sections from naïve mice. We acknowledge the Pulmonary Morphology Core at Washington University School of Medicine for tissue sectioning and slide imaging. This study was supported by the NIH (R01 AI157155, HHSN75N93019C00074, and T32 AI007172), NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract HHSN272201400008C and NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contract 75N93021C00014, and the Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. This work also was supported by the Alafi Neuroimaging Laboratory, the Hope Center for Neurological Disorders, and NIH Shared Instrumentation Grant (S10 RR0227552).
Publisher Copyright:
© 2022 The Authors, some rights reserved
PY - 2022/2/2
Y1 - 2022/2/2
N2 - Although mRNA vaccines encoding the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevent COVID-19, the emergence of new viral variants jeopardizes their efficacy. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike protein) or modified (mRNA-1273.351, designed for B.1.351 spike protein) Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Mice were immunized with either high-dose or low-dose formulations of the mRNA vaccines, where low-dose vaccination modeled suboptimal immune responses. Immunization with formulations at either dose induced neutralizing antibodies in serum against ancestral SARS-CoV-2 WA1/2020 and several virus variants, although serum titers were lower against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. However, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, showed breakthrough lung infections with B.1.617.2 and development of pneumonia in K18-hACE2 mice. Thus, in individuals with reduced immunity after mRNA vaccination, breakthrough infection and disease may occur with some SARS-CoV-2 variants.
AB - Although mRNA vaccines encoding the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevent COVID-19, the emergence of new viral variants jeopardizes their efficacy. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike protein) or modified (mRNA-1273.351, designed for B.1.351 spike protein) Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Mice were immunized with either high-dose or low-dose formulations of the mRNA vaccines, where low-dose vaccination modeled suboptimal immune responses. Immunization with formulations at either dose induced neutralizing antibodies in serum against ancestral SARS-CoV-2 WA1/2020 and several virus variants, although serum titers were lower against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. However, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, showed breakthrough lung infections with B.1.617.2 and development of pneumonia in K18-hACE2 mice. Thus, in individuals with reduced immunity after mRNA vaccination, breakthrough infection and disease may occur with some SARS-CoV-2 variants.
UR - http://www.scopus.com/inward/record.url?scp=85124056420&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.abm3302
DO - 10.1126/scitranslmed.abm3302
M3 - Article
C2 - 34846168
AN - SCOPUS:85124056420
SN - 1946-6234
VL - 14
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 630
M1 - eabm3302
ER -