Developers of COVID-19 vaccines need inspiration, and it may come from cancer researchers. And why not? Viruses and cancers share certain behaviors to help them visit woe upon humankind. So, it seems only fair that vaccine developers and cancer researchers should identify and exploit concepts and methods with cross-disciplinary potential.
For example, a computational tool developed by cancer researchers at Children’s Hospital of Philadelphia (CHOP) has been adapted to identify regions of the SARS-CoV-2 virus that would be vulnerable to newly developed vaccines. Originally, the tool served to identify highly specific biological targets in neuroblastoma tumors that could inform the development of engineered T cells.
The tool, developed and refined by Mark Yarmarkovich, PhD, a researcher in the CHOP laboratory of John M. Maris, MD, prioritizes viral targets based on their ability to stimulate a lasting immune response. Also, highly desirable targets are those predicted to be in the vast majority of the human population.
In a paper that appeared in Cell Reports Medicine, the Maris team described how the tool has been used to identify regions of the SARS-CoV-2 virus to target with a vaccine. The paper, titled, “Identification of SARS-CoV-2 Vaccine Epitopes Predicted to Induce Long-term Population-Scale Immunity,” presents a vaccine concept that could specifically target specific vulnerabilities of SARS-CoV-2 and engage a robust adaptive immune response in the vast majority of the population.
To increase the likelihood that a vaccine is both safe and effective, the researchers looked for regions of SARS-CoV-2 that would stimulate a memory T-cell response that, when paired with the right B cells, would drive memory B-cell formation and provide lasting immunity and do so across the majority of human genomes. The researchers targeted regions of SARS-CoV-2 that are present across multiple related coronaviruses, as well as new mutations that increase infectivity, while also ensuring that those regions were as dissimilar as possible from sequences naturally occurring in humans to maximize safety.
“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 MHC class I and II across the vast majority of the population,” the article’s authors wrote. “We propose 65 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.”
Now that the researchers have proposed a list of 65 peptide sequences that, when targeted, offer the greatest probability of providing population-scale immunity, they have started testing various combinations of a dozen or so of these sequences in mouse models to assess their safety and effectiveness.
“Our team decided to use the tools we developed to identify unique aspects of childhood cancers that can be targeted with immunotherapies and apply those same tools to identify the right protein sequences to target in SARS-CoV-2,” said Maris, a pediatric oncologist at CHOP and the senior author of the current study. “We think our approach provides a roadmap for a vaccine that would be both safe and effective and could be produced at scale.”
The COVID-19 pandemic has led to an urgent need for the development of a safe and effective vaccine against SARS-CoV-2, the virus that causes the COVID-19 disease. An optimally designed vaccine maximizes a long-lasting immune response, while minimizing adverse reactions, autoimmunity, or disease exacerbation.
“With the third epidemic in the past two decades underway, all originating from the coronavirus family, these viruses will continue to threaten the human population and necessitate the need for prophylactic measures against future outbreaks,” said Yarmarkovich. “A subset of the sequences selected in our study are derived from viral regions that are very similar to other coronaviruses, and thus our approach, if successful, could lead to protection against not only SARS-CoV-2 but also other coronaviruses that might emerge in the future.”
