TY - JOUR
T1 - mRNA-1273 and Ad26.COV2.S vaccines protect against the B.1.621 variant of SARS-CoV-2
AU - Darling, Tamarand L.
AU - Ying, Baoling
AU - Whitener, Bradley
AU - VanBlargan, Laura A.
AU - Bricker, Traci L.
AU - Liang, Chieh Yu
AU - Joshi, Astha
AU - Bamunuarachchi, Gayan
AU - Seehra, Kuljeet
AU - Schmitz, Aaron J.
AU - Halfmann, Peter J.
AU - Kawaoka, Yoshihiro
AU - Elbashir, Sayda M.
AU - Edwards, Darin K.
AU - Thackray, Larissa B.
AU - Diamond, Michael S.
AU - Boon, Adrianus C.M.
N1 - Funding Information:
We thank Florian Krammer and Ali Ellebedy for the plasmid and recombinant S protein, respectively. This study was supported by the NIH (R01 AI157155 and U01 AI151810), NIAID Centers of Excellence for Influenza Research and Response [CEIRR] contracts 75N93021C00014 and 75N93021C00016, and the Collaborative Influenza Vaccine Innovation Centers [CIVIC] contract 75N93019C00051. It was also supported, in part, by the National Institutes of Allergy and Infectious Diseases Center for Research on Influenza Pathogenesis (HHSN272201400008C) and the Japan Program for Infectious Diseases Research and Infrastructure (JP21wm0125002) from the Japan Agency for Medical Research and Development (AMED). T.L.B. B.Y. B.W. C.-Y.L. L.A.V. G.B. and T.L.D. performed mouse and hamster experiments. T.L.B. B.Y. and T.L.D. quantified virus titers in collected tissues. K.S. A.J. and B.W. determined viral load by real-time quantitative RT-PCR. Y.K. and P.J.H. isolated, expanded, and sequenced the B.1.621 virus. T.L.D. and L.A.V. performed the virus neutralization assays. M.S.D. A.C.M.B. T.L.D. L.B.T. and B.Y. analyzed the data. A.C.M.B. B.Y. and M.S.D. performed the statistical analysis. A.C.M.B. and M.S.D. had unrestricted access to all data. A.C.M.B. and M.S.D. wrote the first draft of the manuscript, and all authors reviewed and edited the final version. All authors agreed to submit the manuscript, read and approved the final draft, and take full responsibility of its content. The A.C.M.B. laboratory has received unrelated funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences, Inc. and Nano Targeting & Therapy Biopharma, Inc. The A.C.M.B. laboratory has received funding support from AbbVie, Inc. for the commercial development of SARS-CoV-2 mAbs. M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, and Carnival Corporation and is on the Scientific Advisory Boards of Moderna and Immunome. The M.S.D. laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Kaleido, and Emergent BioSolutions and past support from Moderna not related to these studies. S.M.E. and D.K.E. are employees of and shareholders in Moderna, Inc.
Funding Information:
We thank Florian Krammer and Ali Ellebedy for the plasmid and recombinant S protein, respectively. This study was supported by the NIH ( R01 AI157155 and U01 AI151810 ), NIAID Centers of Excellence for Influenza Research and Response [CEIRR] contracts 75N93021C00014 and 75N93021C00016 , and the Collaborative Influenza Vaccine Innovation Centers [CIVIC] contract 75N93019C00051 . It was also supported, in part, by the National Institutes of Allergy and Infectious Diseases Center for Research on Influenza Pathogenesis ( HHSN272201400008C ) and the Japan Program for Infectious Diseases Research and Infrastructure ( JP21wm0125002 ) from the Japan Agency for Medical Research and Development (AMED).
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/5/13
Y1 - 2022/5/13
N2 - Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, viral variants with greater transmissibility or immune-evasion properties have arisen, which could jeopardize recently deployed vaccine- and antibody-based countermeasures. Methods: Here, we evaluated in mice and hamsters the efficacy of a pre-clinical version of the Moderna mRNA vaccine (mRNA-1273) and the Johnson & Johnson recombinant adenoviral-vectored vaccine (Ad26.COV2.S) against the B.1.621 (Mu) variant of SARS-CoV-2, which contains spike mutations T95I, Y144S, Y145N, R346K, E484K, N501Y, D614G, P681H, and D950N. Findings: Immunization of 129S2 and K18-human ACE2 transgenic mice with the mRNA-1273 vaccine protected against weight loss, lung infection, and lung pathology after challenge with the B.1.621 or WA1/2020 N501Y/D614G SARS-CoV-2 strain. Similarly, immunization of 129S2 mice and Syrian hamsters with a high dose of Ad26.COV2.S reduced lung infection after B.1.621 virus challenge. Conclusions: Thus, immunity induced by the mRNA-1273 or Ad26.COV2.S vaccine can protect against the B.1.621 variant of SARS-CoV-2 in multiple animal models. Funding: This study was supported by the NIH (R01 AI157155 and U01 AI151810), NIAID Centers of Excellence for Influenza Research and Response [CEIRR] contracts 75N93021C00014 and 75N93021C00016, and the Collaborative Influenza Vaccine Innovation Centers [CIVIC] contract 75N93019C00051. It was also supported, in part, by the National Institutes of Allergy and Infectious Diseases Center for Research on Influenza Pathogenesis (HHSN272201400008C) and the Japan Program for Infectious Diseases Research and Infrastructure (JP21wm0125002) from the Japan Agency for Medical Research and Development (AMED).
AB - Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, viral variants with greater transmissibility or immune-evasion properties have arisen, which could jeopardize recently deployed vaccine- and antibody-based countermeasures. Methods: Here, we evaluated in mice and hamsters the efficacy of a pre-clinical version of the Moderna mRNA vaccine (mRNA-1273) and the Johnson & Johnson recombinant adenoviral-vectored vaccine (Ad26.COV2.S) against the B.1.621 (Mu) variant of SARS-CoV-2, which contains spike mutations T95I, Y144S, Y145N, R346K, E484K, N501Y, D614G, P681H, and D950N. Findings: Immunization of 129S2 and K18-human ACE2 transgenic mice with the mRNA-1273 vaccine protected against weight loss, lung infection, and lung pathology after challenge with the B.1.621 or WA1/2020 N501Y/D614G SARS-CoV-2 strain. Similarly, immunization of 129S2 mice and Syrian hamsters with a high dose of Ad26.COV2.S reduced lung infection after B.1.621 virus challenge. Conclusions: Thus, immunity induced by the mRNA-1273 or Ad26.COV2.S vaccine can protect against the B.1.621 variant of SARS-CoV-2 in multiple animal models. Funding: This study was supported by the NIH (R01 AI157155 and U01 AI151810), NIAID Centers of Excellence for Influenza Research and Response [CEIRR] contracts 75N93021C00014 and 75N93021C00016, and the Collaborative Influenza Vaccine Innovation Centers [CIVIC] contract 75N93019C00051. It was also supported, in part, by the National Institutes of Allergy and Infectious Diseases Center for Research on Influenza Pathogenesis (HHSN272201400008C) and the Japan Program for Infectious Diseases Research and Infrastructure (JP21wm0125002) from the Japan Agency for Medical Research and Development (AMED).
KW - Ad26.COV2.S
KW - Pre-clinical research
KW - SARS-CoV-2
KW - Syrian hamster
KW - in vivo vaccine efficacy studies
KW - mRNA-1273
KW - mouse
UR - http://www.scopus.com/inward/record.url?scp=85129698753&partnerID=8YFLogxK
U2 - 10.1016/j.medj.2022.03.009
DO - 10.1016/j.medj.2022.03.009
M3 - Article
C2 - 35584653
AN - SCOPUS:85129698753
SN - 2666-6359
VL - 3
SP - 309-324.e6
JO - Med
JF - Med
IS - 5
ER -