NIAID-Led Study Indicates SARS-CoV-2 Specific CD8+T Cell Responses Generally Effective Against Variants But More Study Needed

NIAID-Led Study Indicates SARS-CoV-2 Specific CD8+T Cell Responses Generally Effective Against Variants But More Study Needed

The National Institute of Allergy and Infectious Diseases (NIAID) recently announced promising results from a small but important study involving 30 recovered COVID-19 patients infected with the initial virus. NIAID, part of the National Institutes of Health (NIH), has been concerned that the emergence of SARS-CoV-2 variants, such as those out of South Africa, Brazil or the United Kingdom, could actually evade protective immune responses generated by prior infection or vaccination, potentially making re-infection more likely or vaccination less effective. The consequences of such a reality could be dire, hence NIAID organized a study to investigate this possibility. Led by NIAID’s Andrew Redd, PhD, and scientists from Johns Hopkins University School of Medicine, Johns Hopkins Bloomberg School of Public Health and the Immunomics-focused venture Immunoscope, a study team analyzed blood cell samples from 30 people who had contracted and recovered from COVID-19 prior to the emergence of virus variants, which reportedly emerged in late 2020. NIAID recently reported in a press entry that the team found that one key player in the immune response to SARS-CoV-2, that is the CD8+ T cell—remained active against the virus. 

NIAID recently summarized results of this small but important study titled AD Redd et al. CD8+ T cell responses in COVID-19 convalescent individuals target conserved epitopes from multiple prominent SARS-CoV-2 circulating variants. Open Forum Infectious Diseases DOI: 10.1093/ofid/ofab143 (2021).

The results have what TrialSite would consider important implications. Many have feared that vaccines, for example, will not generally be effective against emerging variants. However, in this study, the NIAID and collaborators verify at least in part a study already completed by La Jolla Institute for Immunology in San Diego, which at the beginning of March uploaded a study to bioRxiv showcasing similar results.

The Key Question

A key study question: can CD8+ T cells in the blood of recovered COVID-19 patients infected with the initial virus continue to recognize three (3) SARS-CoV-2 variants: B.1.1.7, first detected in the UK; B.1.351, originally found in the Republic of South Africa; and B.1.1.248, first tracked in Brazil.

NIAID reports that each of these variants has mutations throughout the virus, and especially in the virus’ spike protein that it utilizes to connect with and enter into the host cells. Mutations in this spike protein region could make it less recognizable to T cells and neutralizing antibodies, which are produced by the immune system’s B cells following infection or vaccination.

The Levels of Immune Response Necessary Still Unknown

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, scientists assume that strong and broad responses from both antibodies and T cells are required to mount an effective immune response. CD8+ T cells limit infection by recognizing parts of the virus protein presented on the surface of infected cells and killing those cells.

CD8+T Cells Recognize Nearly All Mutations in Variants

In their study of recovered COVID-19 patients, 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. While larger studies are needed, the researchers note that their findings suggest that the T cell response in convalescent individuals, and most likely in vaccines, 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.

Funding

Funding for this study came from NIAID grants as well as by a National Heart Lung and Blood Institute Grant (also part of the NIH).

Lead Research/Investigator

Andrew D Redd, PhDDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Other authors can be viewed here

Call to Action: Dr. Anthony S. Fauci, NIAID Director and Chief, Laboratory of Immunoregulation, is available for comment on the study as is Dr. Andrew Redd, staff scientists in the Laboratory of Immunoregulation.

Responses