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March 12, 2021Open Access

Chimeric spike mRNA vaccines completely protect aged mice against diverse coronaviruses unlike monovalent SARS-CoV-2 vaccines.

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Why the study?

The emergence of SARS-CoV and SARS-CoV-2 highlighted the need to develop universal vaccination strategies against the broader Sarbecovirus subgenus.

Does chimeric spike mRNA vaccination protect against Sarbecovirus challenge in vulnerable aged mice?

Population

Vulnerable aged mice

Comparison

Chimeric spike mRNA vaccines vs SARS-CoV-2 mRNA vaccination

Design

Preclinical animal challenge study

Key result

Chimeric spike mRNA vaccines completely protected aged mice against challenge from SARS-CoV, SARS-CoV-2, and bat coronaviruses, whereas monovalent SARS-CoV-2 vaccines resulted in breakthrough infections with heterologous viruses.

Authors

DMDavid R. MartinezASAlexandra SchäferSLSarah R. Leist

Discussion

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Overview

Supports chimeric spike vaccine development for broad Sarbecovirus protection; leaves open human translation and clinical efficacy.

Structured PICO

Does chimeric spike mRNA vaccination protect against Sarbecovirus challenge in vulnerable aged mice?

P
Population
Aged mice evaluated for protection against epidemic, zoonotic, and pandemic SARS-like viruses following vaccination.
I
Intervention
Chimeric spike mRNA vaccines (Chimerized RBD, NTD, and S2 spike mRNA-LNPs)
C
Comparator
SARS-CoV-2 mRNA vaccination
O
Outcome
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-1surrogate

Multiplexed-chimeric spike mRNA vaccines can prevent SARS-like zoonotic coronavirus infections with pandemic potential in mice.

Limitations

  • Potential formation of heterotrimers not present in the intended vaccine formulation
  • Unknown if chimeric mRNA-LNP vaccines generate heterotrimers in vivo

Cite This Study

Martinez et al. (2021) studied Sarbecovirus infection. Chimeric spike mRNA-LNP vaccines vs. Monovalent SARS-CoV-2 mRNA vaccine or norovirus GII capsid vaccine was evaluated on Protection against weight loss and viral replication following Sarbecovirus challenge. Chimeric spike mRNA vaccines completely protected aged mice against challenge from SARS-CoV, SARS-CoV-2, and bat coronaviruses, whereas monovalent SARS-CoV-2 vaccines resulted in breakthrough infections with heterologous viruses.

synapsesocial.com/papers/6aa78c863aaa4d3bb544b2b1https://doi.org/10.1101/2021.03.11.434872
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1A Single Chimeric Spike Antigen Induces Pan-Sarbecovirus Immunity2024 · 1 citations
  2. 2Nonstabilized SARS-CoV-2 spike mRNA vaccination induces broadly neutralizing antibodies in nonhuman primates2025 · 4 citations
  3. 3Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine2024 · 33 citations
  4. 4Multivalent S2-subunit Vaccines Provide Broad Protection Against Clade 1 Sarbecoviruses2024
  5. 5Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice2025 · 21 citations