COVID-19 Story Tip: Profiles of Immune Cells Show Defense Against COVID-19 Mutants Similar to Original Virus

04/07/2021

In January, an international research team — led by Johns Hopkins Medicine and in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and ImmunoScape, a U.S.-Singapore biotechnology company — published one of the most comprehensive profiles to date of T lymphocytes (more commonly known as T cells), the immune system cells that help protect us against SARS-CoV-2, the virus that causes COVID-19. The researchers felt that better defining which T cells interact with which specific portions of the virus could help accelerate the development of next-generation, more effective vaccines.

New variants of SARS-CoV-2 continue to spring up around the world, raising concerns that current vaccines — designed to induce an immune response by recognizing spike proteins of the pandemic’s original virus — might not provide sufficient defense against a mutated strain. This could potentially make COVID-19 re-infection more likely or vaccination less effective.

To address these concerns, the same researchers who profiled the T cells responding to the original SARS-CoV-2 have done a second study, this time characterizing whether the immune cells also respond to three variant virus strains.

The team's findings, reported March 30 in the journal Open Forum Infectious Diseases, show that the T cells can get the job done.

The latest research used data generated from samples collected for the first study — blood cells taken from 30 convalescent patients who had recovered from mild to moderate cases of COVID-19. The researchers used the data to assess how likely a specific type of T cell — known as a CD8+ T cell (commonly called a “killer T cell” for its ability to eliminate cells that are infected with viruses) would recognize the three main SARS-CoV-2 variants that emerged in the past year in the United Kingdom (B.1.1.7), South Africa (B.1.351) and Brazil (B.1.1.248).

CD8+ T cells are covered in protein complexes called T cell receptors (TCRs) that bind to a specific protein fragment, known as an antigen, derived from a foreign body such as a virus. When this binding occurs, the T cell becomes activated and triggers an immune response against the invader. The ability of a specific TCR to recognize its target antigen defines that response.

In the earlier study assessing T cell response to the original SARS-CoV-2 in convalescent patients, the researchers tagged and identified the various types of CD8+ T cells specific for different parts of SARS-CoV-2. This enabled them to determine which of the viral antigens were targeted by the T cells.

Identifying those targeted antigens told the researchers which of the three SARS-CoV-2 variants to examine in the latest study. This time, they wanted to assess whether the genetic mutations associated with the variant strains might affect T cell recognition of the targets.

What they discovered was that the specific CD8+ T cells targets from the original SARS-CoV-2 remained virtually unchanged for all three mutant strains.

This finding is good news, the researchers say, because it suggests that T cell response to these viral targets in the convalescent patients studied — and most likely, in people who have been fully vaccinated — will not be greatly affected by the mutations found in the variants.

“Therefore, the vaccines currently being distributed worldwide should offer a reasonable measure of protection from either infection or serious disease caused by the three variant viruses and hopefully, any others that may emerge,” says study lead author Andrew Redd, Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine and staff scientist at NIAID.

Redd is available for interviews.