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 S.
N1 - 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 - https://www.scopus.com/pages/publications/85124056420
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 -