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A SARS-CoV-2 Vaccination Strategy Focused on Population-Scale Immunity

28 Pages Posted: 14 Apr 2020 Publication Status: Review Complete

See all articles by Mark Yarmarkovich

Mark Yarmarkovich

Children’s Hospital of Philadelphia - Division of Oncology; Children’s Hospital of Philadelphia - Center for Childhood Cancer Research; University of Pennsylvania - Perelman School of Medicine

John M. Warrington

Children’s Hospital of Philadelphia - Division of Oncology

Alvin Farrel

Children’s Hospital of Philadelphia - Division of Oncology; Children’s Hospital of Philadelphia - Center for Childhood Cancer Research

John M. Maris

Children’s Hospital of Philadelphia - Division of Oncology; Children’s Hospital of Philadelphia - Center for Childhood Cancer Research; University of Pennsylvania - Perelman School of Medicine

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Abstract

Here we propose a vaccination strategy for SARS-CoV-2 based on identification of both highly conserved regions of the virus and newly acquired adaptations that are presented by MHC class I and II across the vast majority of the population, are highly dissimilar from the human proteome, and are predicted B cell epitopes. We present 65 peptide sequences that we expect to result in a safe and effective vaccine which can be rapidly tested in DNA, mRNA, or synthetic peptide constructs. These include epitopes that are contained within evolutionarily divergent regions of the spike protein reported to increase infectivity through increased binding to the ACE2 receptor, and within a novel furin cleavage site thought to increase membrane fusion. This vaccination strategy specifically targets unique vulnerabilities of SARS-CoV-2 and should engage a robust adaptive immune response in the vast majority of the human population.

Funding: This work was supported by a St. Baldrick’s-Stand Up To Cancer Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT2727) and the Beau Biden Cancer Moonshot Pediatric Immunotherapy Discovery and Development Networ (NCI Grant U54 CA232568). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. This work was also supported by NIH R35 CA220500 and the Giulio D’Angio Endowed Chair and the Quod Erat Demonstrandum (QED) program at the Science Center in Philadelphia.

Keywords: COVID-19, SARS-CoV-2, coronavirus, vaccine, DNA vaccine, RNA vaccine

Suggested Citation

Yarmarkovich, Mark and Warrington, John M. and Farrel, Alvin and Maris, John M., A SARS-CoV-2 Vaccination Strategy Focused on Population-Scale Immunity. Available at SSRN: https://ssrn.com/abstract=3575161 or http://dx.doi.org/10.2139/ssrn.3575161
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Mark Yarmarkovich

Children’s Hospital of Philadelphia - Division of Oncology

34th Street and Civic Center Boulevard
Philadelphia, PA 19104-4399
United States

Children’s Hospital of Philadelphia - Center for Childhood Cancer Research

34th St and Civic Center Blvd
Philadelphia, PA 19104
United States

University of Pennsylvania - Perelman School of Medicine

423 Guardian Drive
Philadelphia, PA 19104
United States

John M. Warrington

Children’s Hospital of Philadelphia - Division of Oncology ( email )

34th Street and Civic Center Boulevard
Philadelphia, PA 19104-4399
United States

Alvin Farrel

Children’s Hospital of Philadelphia - Division of Oncology

34th Street and Civic Center Boulevard
Philadelphia, PA 19104-4399
United States

Children’s Hospital of Philadelphia - Center for Childhood Cancer Research

34th St and Civic Center Blvd
Philadelphia, PA 19104
United States

John M. Maris (Contact Author)

Children’s Hospital of Philadelphia - Division of Oncology ( email )

34th Street and Civic Center Boulevard
Philadelphia, PA 19104-4399
United States

Children’s Hospital of Philadelphia - Center for Childhood Cancer Research ( email )

34th St and Civic Center Blvd
Philadelphia, PA 19104
United States

University of Pennsylvania - Perelman School of Medicine ( email )

423 Guardian Drive
Philadelphia, PA 19104
United States

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