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.
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.
ABSTRACT
Here we propose a SARS-CoV-2 vaccine design concept based on identification of highly conserved regions of the viral genome and newly acquired adaptations, both predicted to generate epitopes presented on major histocompatibility complex (MHC) class I and II across the vast majority of the population. We further prioritize genomic regions that generate highly dissimilar peptides from the human proteome and are also predicted to produce B cell epitopes. We propose sixty-five 33-mer peptide sequences, a subset of which can be tested using DNA or mRNA delivery strategies. These include peptides 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 newly evolved furin cleavage site thought to increase membrane fusion. Validation and implementation of this vaccine concept could specifically target specific vulnerabilities of SARS-CoV-2 and should engage a robust adaptive immune response in the vast majority of the population.