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A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine.
Proc Natl Acad Sci U S A. 2020 12 22; 117(51):32657-32666.PN

Abstract

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8+ and CD4+ T cell responses with S protein-specific killing activity were detected. Upon challenge using a mouse-adapted SARS-CoV-2, virus loads in vaccinated mice were significantly lower, while vaccinated Syrian hamsters revealed protection in a harsh challenge setup using an early-passage human patient isolate. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines.

Authors+Show Affiliations

Product Testing of Immunological Medicinal Products for Veterinary Use, Division of Veterinary Medicine, Paul-Ehrlich-Institut, D-63225 Langen, Germany. German Center for Infection Research, D-63225 Langen, Germany.Product Testing of Immunological Medicinal Products for Veterinary Use, Division of Veterinary Medicine, Paul-Ehrlich-Institut, D-63225 Langen, Germany.Product Testing of Immunological Medicinal Products for Veterinary Use, Division of Veterinary Medicine, Paul-Ehrlich-Institut, D-63225 Langen, Germany. German Center for Infection Research, D-63225 Langen, Germany.Product Testing of Immunological Medicinal Products for Veterinary Use, Division of Veterinary Medicine, Paul-Ehrlich-Institut, D-63225 Langen, Germany.Product Testing of Immunological Medicinal Products for Veterinary Use, Division of Veterinary Medicine, Paul-Ehrlich-Institut, D-63225 Langen, Germany.Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Division of Virology, Paul-Ehrlich-Institut, D-63225 Langen, Germany.Pathogenesis of Respiratory Viruses, Division of Veterinary Medicine, Paul-Ehrlich-Institut, D-63225 Langen, Germany.Division of Virology, Paul-Ehrlich-Institut, D-63225 Langen, Germany.Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.Product Testing of Immunological Medicinal Products for Veterinary Use, Division of Veterinary Medicine, Paul-Ehrlich-Institut, D-63225 Langen, Germany; Michael.Muehlebach@pei.de. German Center for Infection Research, D-63225 Langen, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33257540

Citation

Hörner, Cindy, et al. "A Highly Immunogenic and Effective Measles Virus-based Th1-biased COVID-19 Vaccine." Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 51, 2020, pp. 32657-32666.
Hörner C, Schürmann C, Auste A, et al. A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine. Proc Natl Acad Sci U S A. 2020;117(51):32657-32666.
Hörner, C., Schürmann, C., Auste, A., Ebenig, A., Muraleedharan, S., Dinnon, K. H., Scholz, T., Herrmann, M., Schnierle, B. S., Baric, R. S., & Mühlebach, M. D. (2020). A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine. Proceedings of the National Academy of Sciences of the United States of America, 117(51), 32657-32666. https://doi.org/10.1073/pnas.2014468117
Hörner C, et al. A Highly Immunogenic and Effective Measles Virus-based Th1-biased COVID-19 Vaccine. Proc Natl Acad Sci U S A. 2020 12 22;117(51):32657-32666. PubMed PMID: 33257540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine. AU - Hörner,Cindy, AU - Schürmann,Christoph, AU - Auste,Arne, AU - Ebenig,Aileen, AU - Muraleedharan,Samada, AU - Dinnon,Kenneth H,3rd AU - Scholz,Tatjana, AU - Herrmann,Maike, AU - Schnierle,Barbara S, AU - Baric,Ralph S, AU - Mühlebach,Michael D, Y1 - 2020/11/30/ PY - 2020/12/2/pubmed PY - 2021/1/20/medline PY - 2020/12/1/entrez KW - COVID-19 KW - SARS-CoV-2 KW - Th1 immune bias KW - effective immunity KW - measles vaccine platform SP - 32657 EP - 32666 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 117 IS - 51 N2 - The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8+ and CD4+ T cell responses with S protein-specific killing activity were detected. Upon challenge using a mouse-adapted SARS-CoV-2, virus loads in vaccinated mice were significantly lower, while vaccinated Syrian hamsters revealed protection in a harsh challenge setup using an early-passage human patient isolate. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/33257540/A_highly_immunogenic_and_effective_measles_virus_based_Th1_biased_COVID_19_vaccine_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=33257540 DB - PRIME DP - Unbound Medicine ER -