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Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice.
Science. 2021 08 27; 373(6558):991-998.Sci

Abstract

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and SARS-CoV-2 in 2019 highlights the need to develop universal vaccination strategies against the broader Sarbecovirus subgenus. Using chimeric spike designs, we demonstrate protection against challenge from SARS-CoV, SARS-CoV-2, SARS-CoV-2 B.1.351, bat CoV (Bt-CoV) RsSHC014, and a heterologous Bt-CoV WIV-1 in vulnerable aged mice. Chimeric spike messenger RNAs (mRNAs) induced high levels of broadly protective neutralizing antibodies against high-risk Sarbecoviruses. By contrast, SARS-CoV-2 mRNA vaccination not only showed a marked reduction in neutralizing titers against heterologous Sarbecoviruses, but SARS-CoV and WIV-1 challenge in mice resulted in breakthrough infections. Chimeric spike mRNA vaccines efficiently neutralized D614G, mink cluster five, and the UK B.1.1.7 and South African B.1.351 variants of concern. Thus, multiplexed-chimeric spikes can prevent SARS-like zoonotic coronavirus infections with pandemic potential.

Authors+Show Affiliations

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. david.rafael.martinez@gmail.com rbaric@email.unc.edu.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.Department of Laboratory Medicine and Pathology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. david.rafael.martinez@gmail.com rbaric@email.unc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34214046

Citation

Martinez, David R., et al. "Chimeric Spike mRNA Vaccines Protect Against Sarbecovirus Challenge in Mice." Science (New York, N.Y.), vol. 373, no. 6558, 2021, pp. 991-998.
Martinez DR, Schäfer A, Leist SR, et al. Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice. Science. 2021;373(6558):991-998.
Martinez, D. R., Schäfer, A., Leist, S. R., De la Cruz, G., West, A., Atochina-Vasserman, E. N., Lindesmith, L. C., Pardi, N., Parks, R., Barr, M., Li, D., Yount, B., Saunders, K. O., Weissman, D., Haynes, B. F., Montgomery, S. A., & Baric, R. S. (2021). Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice. Science (New York, N.Y.), 373(6558), 991-998. https://doi.org/10.1126/science.abi4506
Martinez DR, et al. Chimeric Spike mRNA Vaccines Protect Against Sarbecovirus Challenge in Mice. Science. 2021 08 27;373(6558):991-998. PubMed PMID: 34214046.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice. AU - Martinez,David R, AU - Schäfer,Alexandra, AU - Leist,Sarah R, AU - De la Cruz,Gabriela, AU - West,Ande, AU - Atochina-Vasserman,Elena N, AU - Lindesmith,Lisa C, AU - Pardi,Norbert, AU - Parks,Robert, AU - Barr,Maggie, AU - Li,Dapeng, AU - Yount,Boyd, AU - Saunders,Kevin O, AU - Weissman,Drew, AU - Haynes,Barton F, AU - Montgomery,Stephanie A, AU - Baric,Ralph S, Y1 - 2021/06/22/ PY - 2021/03/11/received PY - 2021/06/15/accepted PY - 2021/7/3/pubmed PY - 2021/9/11/medline PY - 2021/7/2/entrez SP - 991 EP - 998 JF - Science (New York, N.Y.) JO - Science VL - 373 IS - 6558 N2 - The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and SARS-CoV-2 in 2019 highlights the need to develop universal vaccination strategies against the broader Sarbecovirus subgenus. Using chimeric spike designs, we demonstrate protection against challenge from SARS-CoV, SARS-CoV-2, SARS-CoV-2 B.1.351, bat CoV (Bt-CoV) RsSHC014, and a heterologous Bt-CoV WIV-1 in vulnerable aged mice. Chimeric spike messenger RNAs (mRNAs) induced high levels of broadly protective neutralizing antibodies against high-risk Sarbecoviruses. By contrast, SARS-CoV-2 mRNA vaccination not only showed a marked reduction in neutralizing titers against heterologous Sarbecoviruses, but SARS-CoV and WIV-1 challenge in mice resulted in breakthrough infections. Chimeric spike mRNA vaccines efficiently neutralized D614G, mink cluster five, and the UK B.1.1.7 and South African B.1.351 variants of concern. Thus, multiplexed-chimeric spikes can prevent SARS-like zoonotic coronavirus infections with pandemic potential. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/34214046/Chimeric_spike_mRNA_vaccines_protect_against_Sarbecovirus_challenge_in_mice. L2 - https:///www.science.org/doi/10.1126/science.abi4506?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -