Tags

Type your tag names separated by a space and hit enter

SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern.
Elife. 2022 02 22; 11E

Abstract

Despite mass public health efforts, the SARS-CoV2 pandemic continues as of late 2021 with resurgent case numbers in many parts of the world. The emergence of SARS-CoV2 variants of concern (VoCs) and evidence that existing vaccines that were designed to protect from the original strains of SARS-CoV-2 may have reduced potency for protection from infection against these VoC is driving continued development of second-generation vaccines that can protect against multiple VoC. In this report, we evaluated an alphavirus-based replicating RNA vaccine expressing Spike proteins from the original SARS-CoV-2 Alpha strain and recent VoCs delivered in vivo via a lipid inorganic nanoparticle. Vaccination of both mice and Syrian Golden hamsters showed that vaccination induced potent neutralizing titers against each homologous VoC but reduced neutralization against heterologous challenges. Vaccinated hamsters challenged with homologous SARS-CoV2 variants exhibited complete protection from infection. In addition, vaccinated hamsters challenged with heterologous SARS-CoV-2 variants exhibited significantly reduced shedding of infectious virus. Our data demonstrate that this vaccine platform can be updated to target emergent VoCs, elicits significant protective immunity against SARS-CoV2 variants and supports continued development of this platform.

Links

PMC Free PDF

Authors+Show Affiliations

Hawman DW
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United States.
Meade-White K
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United States.
Archer J
HDT Bio, Seattle, United States.
Leventhal SS
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United States.
Wilson D
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United States.
Shaia C
Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United States.
Randall S
Department of Microbiology, University of Washington School of Medicine, Seattle, United States.
Khandhar AP
HDT Bio, Seattle, United States.
Krieger K
HDT Bio, Seattle, United States.
Hsiang TY
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, United States.
Gale M
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, United States.
Berglund P
HDT Bio, Seattle, United States.
Fuller DH
Department of Microbiology, University of Washington School of Medicine, Seattle, United States.
Feldmann H
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United States.
Erasmus JH
HDT Bio, Seattle, United States. Department of Microbiology, University of Washington School of Medicine, Seattle, United States.

MeSH

AnimalsAntibodies, NeutralizingCOVID-19COVID-19 VaccinesCricetinaeHumansMiceRNA, ViralSARS-CoV-2Spike Glycoprotein, CoronavirusVaccines, SyntheticmRNA Vaccines

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

35191378

Citation

Hawman, David W., et al. "SARS-CoV2 Variant-specific Replicating RNA Vaccines Protect From Disease Following Challenge With Heterologous Variants of Concern." ELife, vol. 11, 2022.
Hawman DW, Meade-White K, Archer J, et al. SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern. Elife. 2022;11.
Hawman, D. W., Meade-White, K., Archer, J., Leventhal, S. S., Wilson, D., Shaia, C., Randall, S., Khandhar, A. P., Krieger, K., Hsiang, T. Y., Gale, M., Berglund, P., Fuller, D. H., Feldmann, H., & Erasmus, J. H. (2022). SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern. ELife, 11. https://doi.org/10.7554/eLife.75537
Hawman DW, et al. SARS-CoV2 Variant-specific Replicating RNA Vaccines Protect From Disease Following Challenge With Heterologous Variants of Concern. Elife. 2022 02 22;11 PubMed PMID: 35191378.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern. AU - Hawman,David W, AU - Meade-White,Kimberly, AU - Archer,Jacob, AU - Leventhal,Shanna S, AU - Wilson,Drew, AU - Shaia,Carl, AU - Randall,Samantha, AU - Khandhar,Amit P, AU - Krieger,Kyle, AU - Hsiang,Tien-Ying, AU - Gale,Michael, AU - Berglund,Peter, AU - Fuller,Deborah Heydenburg, AU - Feldmann,Heinz, AU - Erasmus,Jesse H, Y1 - 2022/02/22/ PY - 2021/11/13/received PY - 2022/02/17/accepted PY - 2022/2/23/pubmed PY - 2022/4/8/medline PY - 2022/2/22/entrez KW - COVID-19 KW - RNA vaccine KW - hamster KW - immunology KW - infectious disease KW - inflammation KW - microbiology KW - replicon KW - vaccine JF - eLife JO - Elife VL - 11 N2 - Despite mass public health efforts, the SARS-CoV2 pandemic continues as of late 2021 with resurgent case numbers in many parts of the world. The emergence of SARS-CoV2 variants of concern (VoCs) and evidence that existing vaccines that were designed to protect from the original strains of SARS-CoV-2 may have reduced potency for protection from infection against these VoC is driving continued development of second-generation vaccines that can protect against multiple VoC. In this report, we evaluated an alphavirus-based replicating RNA vaccine expressing Spike proteins from the original SARS-CoV-2 Alpha strain and recent VoCs delivered in vivo via a lipid inorganic nanoparticle. Vaccination of both mice and Syrian Golden hamsters showed that vaccination induced potent neutralizing titers against each homologous VoC but reduced neutralization against heterologous challenges. Vaccinated hamsters challenged with homologous SARS-CoV2 variants exhibited complete protection from infection. In addition, vaccinated hamsters challenged with heterologous SARS-CoV-2 variants exhibited significantly reduced shedding of infectious virus. Our data demonstrate that this vaccine platform can be updated to target emergent VoCs, elicits significant protective immunity against SARS-CoV2 variants and supports continued development of this platform. SN - 2050-084X UR - https://www.unboundmedicine.com/medline/citation/35191378/SARS_CoV2_variant_specific_replicating_RNA_vaccines_protect_from_disease_following_challenge_with_heterologous_variants_of_concern_ DB - PRIME DP - Unbound Medicine ER -