Researchers repurpose cancer immunotherapy tools for COVID-19 vaccine research

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Researchers at Children’s Hospital of Philadelphia (CHOP; PA, USA) have repurposed tools typically used for the development of cancer immunotherapies to identify regions of SARS-CoV-2 to target with a vaccine, employing the same approach used to trigger an immune response against cancer cells to stimulate an immune response against the virus. The researchers believe that this strategy, described in Cell Reports Medicine, could result in a vaccine that provides long-term protection across the human population.

The COVID-19 pandemic has created an urgent need for a vaccine that protects the human population from SARS-CoV-2 by driving a long-lasting immune response to the virus.

In response to this need, a team at CHOP decided to apply their expertise in cancer immunotherapy to investigate potential vaccine targets on SARS-CoV-2.

“In many ways, cancer behaves like a virus, so 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,” explained senior author John Maris (CHOP’s Cancer Center) “By adapting the computational tools developed and now refined by lead author Mark Yarmarkovich, PhD in the Maris Lab, we can now prioritize viral targets based on their ability to stimulate a lasting immune response, predicted to be in the vast majority of the human population. We think our approach provides a roadmap for a vaccine that would be both safe and effective and could be produced at scale.”

In order to increase the likelihood that a resulting vaccine is both safe and effective, the researchers searched for regions that would stimulate a memory T cell response that, when paired with the right B cells, would trigger memory B cell formation and provide lasting immunity across the majority of human genomes.

The regions that they targeted are present across multiple related coronaviruses, and include new mutations that increase infectivity. To maximize safety, the researchers ensured that these regions were dissimilar to sequences naturally occurring in humans.

As a result of this study, the team at CHOP have presented a list of 65 peptide sequences that hold the potential for a pathway to a vaccine that provides population scale immunity to COVID-19.

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Moving forward, the researchers are testing various combinations of these sequences in mouse models to assess their safety and efficacy.

“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,” commented 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.”

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Sources: Yarmarkovich M, Warrington JM, Farrel A, Maris JM. A SARS-CoV-2 Vaccination Strategy Focused on Population-Scale Immunity. Cell Reports Medicine doi:10.1101/2020.03.31.018978 (2020); www.eurekalert.org/pub_releases/2020-06/chop-sit060820.php

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