Pitt team sheds light on how COVID-19 escapes immune destruction

SARS-CoV-2, the virus that causes COVID-19, has acquired mutations, giving rise to new strains that are complicating the effort to put an end to the pandemic. But it’s unclear exactly how—or even if—these mutations might hamper COVID-19 antibody treatments and vaccines.

Researchers at the University of Pittsburgh School of Medicine are offering some insights that could help drug and vaccine developers tweak their COVID-19 remedies over time to stay ahead of the virus.

They discovered that SARS-CoV-2 evolves over time to evade the immune response to the virus. Specifically, it deletes part of the genetic code for the spike protein on its surface, which in turn prevents some antibodies from attaching to the virus and neutralizing it. They published the findings in the journal Science.

Because the spike protein is COVID-19’s ticket to infecting healthy cells, it has been a prime target for treatments and vaccines. But if part of its genetic code disappears “in an important part of the virus that the antibody ‘sees,’ then it’s gone for good,” said senior author Paul Duprex, Ph.D., director of the Center for Vaccine Research at the University of Pittsburgh, in a statement.

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Duprex’s team discovered the neutralization-resistant genetic deletions while studying a sample from an immuno-compromised patient who battled COVID-19 for more than two months before dying of the disease. They wondered whether other patients might have the same variant, so they consulted an international database of SARS-CoV-2 genomic sequences.

The Pitt researchers discovered several examples of genetic deletions, all of which changed the shape of the spike protein just enough so antibodies couldn’t recognize it—but not enough to hamper the virus’s ability to infect healthy cells. The fast-spreading U.K. variant of COVID-19 was among those found to have these deletions.

The U.K. variant of COVID-19 was discovered in the fall and has since been found to be circulating in the U.S. The Centers for Disease Control and Prevention predicted last month that the variant, which is more infectious than previous versions of the virus, will be the dominant strain by March.

The precise impact of genetic deletions discovered by the Pitt team on the vaccines and antibody treatments that are on the market now is unclear. Some products may still be effective, the researchers said. For example, they discovered that the strain they identified in the first patient they studied was capable of being neutralized by plasma from other COVID-19 patients.

Vaccine developers are weighing in with research aimed at determining whether their products will prevent the new strains of COVID-19. Last week, Johnson & Johnson said its vaccine was 72% effective in the U.S. in a phase 3 trial but only 57% effective in South Africa, where another aggressive variant is spreading.

The Pitt researchers believe their findings raise important questions that should be addressed in future studies. “Additional circulating … variants have gone virtually unnoticed. Are they intermediates on a pathway of immune evasion? That remains to be determined,” they wrote in the study.

Lead author Kevin McCarthy, Ph.D., assistant professor of molecular biology and molecular genetics at Pitt, added the insights into how SARS-CoV-2 evolves to escape immune destruction could help the life sciences community stay ahead of the virus in the future. “At some point, we’re going to have to start reformulating vaccines, or at least entertain that idea,” he said.