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Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice
- Source :
- Science, bioRxiv, article-version (status) pre, article-version (number) 1
- Publication Year :
- 2021
- Publisher :
- American Association for the Advancement of Science (AAAS), 2021.
-
Abstract
- The emergence of SARS-CoV and SARS-CoV-2 in the 21st century highlights the need to develop universal vaccination strategies against the SARS-related Sarbecovirus subgenus. Using structure-guided chimeric spike designs and multiplexed immunizations, we demonstrate protection against SARS-CoV, SARS-CoV-2, and bat CoV (BtCoV) RsSHC014 challenge in highly vulnerable aged mice. Chimeric spike mRNAs containing N-terminal domain (NTD), and receptor binding domains (RBD) induced high levels of broadly protective neutralizing antibodies against three high-risk sarbecoviruses: SARS-CoV, RsSHC014, and WIV-1. In contrast, SARS-CoV-2 mRNA vaccination not only showed a 10 to >500-fold reduction in neutralizing titers against heterologous sarbecovirus strains, but SARS-CoV challenge in mice resulted in breakthrough infection including measurable lung pathology. Importantly, chimeric spike mRNA vaccines efficiently neutralized both the D614G and the South African B.1.351 variants of concern despite some reduction in neutralization activity. Thus, multiplexed-chimeric spikes may provide a novel strategy to prevent pandemic and SARS-like zoonotic coronavirus infections, while revealing the limited efficacy of SARS-CoV-2 spike vaccines against other sarbecoviruses.
- Subjects :
- Sarbecovirus
0301 basic medicine
Cross Protection
viruses
Antibodies, Viral
Severe Acute Respiratory Syndrome
Virus Replication
Neutralization
Mice
Immunogenicity, Vaccine
0302 clinical medicine
030212 general & internal medicine
Mink
skin and connective tissue diseases
Lung
Mice, Inbred BALB C
Vaccines, Synthetic
Multidisciplinary
biology
Immunogenicity
virus diseases
Vaccination
Titer
Severe acute respiratory syndrome-related coronavirus
Spike Glycoprotein, Coronavirus
Cytokines
Female
Spike (software development)
Antibody
Coronavirus Infections
COVID-19 Vaccines
Recombinant Fusion Proteins
Heterologous
Immunity, Heterologous
Article
Betacoronavirus
03 medical and health sciences
Protein Domains
Immunity
biology.animal
Animals
Messenger RNA
SARS-CoV-2
fungi
COVID-19
Viral Vaccines
Breakthrough infection
biology.organism_classification
Antibodies, Neutralizing
Virology
respiratory tract diseases
body regions
universal coronavirus vaccine
mRNA vaccine
030104 developmental biology
Viral replication
Liposomes
biology.protein
Nanoparticles
SARS-like virus
Subjects
Details
- ISSN :
- 10959203 and 00368075
- Volume :
- 373
- Database :
- OpenAIRE
- Journal :
- Science
- Accession number :
- edsair.doi.dedup.....ee6106d321b50b8144a9ffbc52f64981
- Full Text :
- https://doi.org/10.1126/science.abi4506