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PreprintCited by 101SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections Studiesvaccines and immunoinformatics approaches

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Open access
Wu, Kai, Choi, Angela, Koch, Matthew, Elbashir, Sayda, Ma, LingZhi, Lee, Diana, Woods, Angela, Henry, Carole +17 more·2021·Vaccine
DOI 10.1101/2021.04.13.439482PMC PMC8572694

Preprint — published as 10.1016/j.vaccine.2021.11.001

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several variants have shown decreased susceptibility to neutralization by vaccine-induced immunity, most notably B.1.351 (Beta), although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of 2 updated mRNA vaccines designed to target SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the spike protein found in B.1.351 and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against B.1.351, while mRNA-1273.211 was effective at providing broad cross-variant neutralization. A third (booster) dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are being evaluated in pre-clinical challenge and clinical studies.

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  • An mRNA vaccine that incorporated most of the spike mutations present in the Beta variant (mRNA-1273.351; Moderna) was recently reported to increase both pre-variant and Beta variant-specific neutralizing antibody titres when administered as a booster to mice that had previously been immunized with mRNA-1273.

    “An mRNA vaccine that incorporated most of the spike mutations present in the Beta variant (mRNA-1273.351;Moderna) was recently reported to increase both pre-variant and Beta variant-specific neutralizing antibody titres when administered as a booster to mice that had previously been immunized with mRNA-1273 (ref.246 ).”

    From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [246]

  • A single mRNA vaccine can enable the targeting of multiple microbes or viral variants with a single formulation.

    “and enabling the targeting of multiple microbes or viral variants with a single formulation8.”

    From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [8]

  • Moderna is evaluating the original mRNA-1273 vaccine and updated versions mRNA-1273.351 and mRNA-1273.211 as third dose boosters.

    “At the time of this writing, Moderna is evaluating the original mRNA-1273 vaccine and updated versions of the vaccine as a third dose booster — mRNA-1273.351, which encodes the spike protein from the B.1.351 variant, and mRNA-1273.211, a multivariant vaccine that is a 1:1 mix of mRNA-1273 and mRNA-1273.351 (ref.8).”

    From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [8]

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Authors
Wu, K., Choi, A., Koch, M., Elbashir, S., Ma, L., Lee, D., Woods, A., Henry, C., Palandjian, C., Hill, A., Jani, H., Quinones, J., Nunna, N., O’Connell, S., McDermott, A. B., Falcone, S., Narayanan, E., Colpitts, T., Bennett, H., Corbett, K. S., Seder, R., Graham, B. S., Stewart-Jones, G. B., Carfi, A., & Edwards, D. K.
Affiliations
  • Moderna Therapeutics (United States) (US)
  • National Institutes of Health (US)
ORCID
Venue
Vaccine
Publisher
openRxiv
Published
2021-04-13
Volume
39
Issue
51
Pages
7394-7400
ISSN
0264-410X (ISSN-L)
DOI
10.1101/2021.04.13.439482
PMC
PMC8572694
OpenAlex
W3211902898
Cited by
101
References
49
Citations by year
2026: 3 · 2025: 5 · 2024: 11 · 2023: 10 · 2022: 41 · 2021: 31
FWCI
7.44
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Vaccine (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
Moderna
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
SARS-CoV-2 variants, mRNA vaccines, mRNA-1273, Beta variant, vaccine escape, neutralizing antibodies, booster vaccination, spike protein, COVID-19 vaccines

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