New Study on Cellular Immunity Offers Insight for Future COVID-19 Vaccine Design

Repertoire believes the findings, which provide an updated understanding of viral antigen presentation and epitope selection, may assist in vaccine development for COVID-19.

A new study published in Cell and led by clinical-stage biotech company Repertoire Immune Medicines offers new insight into how cells infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interact with the body’s immune system. The company believes the recent findings, which provide an updated understanding of the process of viral antigen presentation and epitope selection, may assist in vaccine development for coronavirus disease 2019 (COVID-19).

In the study, researchers used a method dubbed “immunopeptidomics,” which allowed them to examine the presentation of the SARS-CoV-2 antigen on infected human cell lines. Using this technique, the investigators identified the presentation of several peptides from non-canonical reading frames of the novel coronavirus’ genome. The researchers found that these peptides were later found to be relevant in disease in both a mouse model as well as human patients with COVID-19.

Taken together, the findings from the assays in the study detected high T cell reactivity to different novel peptides. One peptide generated higher levels of responses in patients with COVID-19 than other immunodominant T cell epitopes previously studied in other research. The insight gained from the results, according to the researchers, may assist in “epitope selection of peptides for immune monitoring and vaccine development for SARS-CoV-2 and other disease areas.”

Investigators from the Sabeti Lab, Broad Institute of MIT and Harvard were involved in the new research. The lead investigator was Pardis Sabeti, M.D., D.Phil. According to a statement on the findings, Repertoire said that the biological significance of the findings in COVID-19-infected patients was identified with the company’s proprietary DECODE™ platform, which allowed for the discovery of T cells that recognized epitopes in recovering patients.

“The insights from this work increase our understanding of the interaction between SARS-CoV-2 and the immune system, and could potentially extend to additional pathogens as well,” said Shira Weingarten-Gabbay, Ph.D., an investigator from the Broad Institute.

Repertoire’s Head of Platform Discovery and Technology, Daniel Pregibon, Ph.D., said in a statement that the research findings offer novel “insights into the nature and dynamics of viral protein expression” as well as presentation in COVID-19.

“We are delighted that we were able to use Repertoire’s technology to demonstrate the relevance of the novel epitopes discovered by the Sabeti Lab’s immunopeptidomics approach, and we look forward to furthering the science in this area to better design next-generation vaccines for COVID-19 and beyond,” he added.

In addition to the company’s research into SARS-CoV-2, Repertoire is also diving into researching novel antigens and T cell receptors in cancer. Late last month, the company collaborated with a research team from the Yale University School Of Medicine to identify antigens expressed in patients with advanced metastatic melanoma. The research will focus on determining which of the discovered antigens “turn on” T cells in the tumor of these patients. Specifically, the collaborative research may identify new antigens and their T cells that could be incorporated into Repertoire’s cell therapy, among other development initiatives.

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