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Study Reveals New Targets for Next-Generation COVID-19 Vaccines and Tests, Beyond Antibodies

August 7, 2020 Coronavirus (Covid-19) No Comments Email Email

Newswise — Atlantic Health System’s Atlantic Center for Research is one of two sites in the nation to conduct an innovative COVID-19 study sponsored by TScan Therapeutics. The researchers have prepublished their results, which identify new targets for COVID-19 vaccines and tests that go beyond the current focus on COVID antibodies.

“This study was designed to focus on T cells, as opposed to the more common focus on B cells, and it has significantly increased our understanding of how the immune system’s T cells mount a response to SARS-Co-V2, the coronavirus that causes COVID-19,” said Angela Alistar, MD, medical director of GI Medical Oncology and the Breakthrough Treatment Center at Atlantic Health System’s Morristown Medical Center and local principal investigator for the study.

B cells and T cells are white blood cells that each take a different approach to fighting infection from bacteria and viruses. B cells produce antibodies to the foreign invader and form memory cells that remember the same pathogen for faster antibody production in future infections. T cells can develop into memory cells, just as B cells can, but they do not produce antibodies. T cells directly kill virus-infected cells and are known as “killer T cells.” Sometimes individuals with a very vigorous T cell immune response will be protected from an invader even though they produce low amounts of antibodies from B cells.

“Killer T cells clear viral infections and may be necessary for long-term immunity to coronaviruses,” said Eric Whitman, MD, medical director, Atlantic Health System Cancer Care and co-investigator on the study. “The T cell immune response is much more difficult to measure than the B cell antibody response and is usually only evaluated in a specialized research setting.”

To conduct the study, physician researchers at Atlantic Health System hospitals drew blood samples from 35 recovered COVID-19 patients who volunteered for the study. The blood samples were sent to TScan Therapeutics, where scientists used their core T cell target identification technology to examine patients’ T cells, in order to determine which parts of the virus these cells were targeting. They found that patients’ T cells recognize the same, relatively small number of targets that are unique to COVID-19 and don’t tend to mutate.

“These findings pave the way for diagnostic tests that detect COVID immunity based on T cells instead of antibodies,” added Dr. Whitman. “Interestingly, TScan also found that 90% of T cells recognize targets outside of the spike protein.”

The spike protein has been the focus of the development of COVID vaccines, including those now in Phase 3 trials. Research has shown that this approach, which is targeted at generating neutralizing antibodies rather than T cells, may not be sufficient to induce long term immunity. The new discoveries suggest that second-generation vaccines will need to incorporate T cell targets if they are to generate lasting COVID-19 immunity.

“COVID-19 vaccine development efforts have been progressing rapidly, but to date remain largely focused on causing a neutralizing antibody response against the virus’ spike protein,” said Gavin MacBeath, PhD, chief scientific officer at TScan. “An increasing body of evidence suggests that a T cell response is important in the defense against COVID-19, and T cells that recognize coronaviruses tend to persist much longer than antibodies. By identifying a short list of the most critical T cell targets, we have provided a roadmap to development of follow-on vaccines.”

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