T Cells of Previously Infected People Still Recognize SARS-CoV-2 Variants

Coronavirus structure
[Source: Andriy Onufriyenko/Getty Images]

As SARS-CoV-2 variants have emerged and spread around the world, a key concern is whether prior infection or vaccination will still be protective against them. To investigate this question, researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and colleagues analyzed blood cell samples from people who had contracted and recovered from COVID-19 prior to the emergence of the new variants. Their study suggests that virtually all anti-SARS-CoV-2 CD8+ T-cell responses should recognize these newly described variants.

The research team was led by NIAID’s Andrew Redd, PhD, and included scientists from Johns Hopkins University School of Medicine, Johns Hopkins Bloomberg School of Public Health and, ImmunoScape. Their study appears in Open Forum Infectious Diseases DOI: 10.1093/ofid/ofab143 (2021).

The investigators looked at CD8+ T cells in the blood of 30 recovered patients, who had been infected with the main virus, and asked if these cells could still recognize three SARS-CoV-2 variants: B.1.1.7, which was first detected in the United Kingdom; B.1.351, originally found in the Republic of South Africa; and B.1.1.248, first seen in Brazil. Each variant has mutations throughout the virus, and, in particular, in the region of the virus’ spike protein. Mutations in this spike protein region could make it less recognizable to T cells and neutralizing antibodies, which are made by the immune system’s B cells following infection or vaccination.

Redd et al. write that “These variants all possess the N501Y mutation in the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, a primary target for neutralizing antibody (NAb) binding. They also all contain unique additional mutations throughout the genome, and are not phylogenetically linked, indicating that they evolved independently.”

Although details about the exact levels and composition of antibody and T-cell responses needed to achieve immunity to SARS-CoV-2 are still unknown, it is assumed that strong and broad responses from both antibodies and T cells are required to mount an effective immune response.

The researchers determined that SARS-CoV-2-specific CD8+ T-cell responses remained largely intact and could recognize virtually all mutations in the variants studied. The researchers note that their findings suggest that the T cell response in convalescent individuals, and most likely in vaccinees, are largely not affected by the mutations found in these three variants, and should offer protection against emerging variants.    

Optimal immunity to SARS-Cov-2 likely requires strong multivalent T-cell responses in addition to neutralizing antibodies and other responses to protect against current SARS-CoV-2 strains and emerging variants, the authors indicate. They stress the importance of monitoring the breadth, magnitude and durability of the anti-SARS-CoV-2 T-cell responses in recovered and vaccinated individuals as part of any assessment to determine if booster vaccinations are needed.  

While Redd et al.’s study is reassuring, the authors note that it is small and all the subjects were from North America. “It will also be important to examine for T cell escape in more diverse HLA types moving forward,” they write.

The authors add that, “Preliminary reports from ongoing Phase 2b/3 vaccine trials performed in the United Kingdom during the rise of B.1.1.7 suggest that the efficacy of spike-based vaccines has not diminished significantly; however, these studies have not been published or peer-reviewed.” This week results from one of those trials was published in The Lancet (Emary, K. et al) and show that the Oxford–AstraZeneca ChAdOx1 nCoV-19 vaccine retains efficacy against the B.1.1.7 variant, but its efficacy is probably somewhat reduced compared with that against the original virus strain.

As Redd et al’s study shows, “It will be important to continue to monitor the breadth, magnitude, and durability of the anti-SARS-CoV-2 T cell responses in recovered and vaccinated individuals as part of any assessment to determine if booster vaccinations are needed,” the authors write.

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