A new study by Johns Hopkins Medicine researchers provides evidence that CD4+ T lymphocytes – immune system cells also known as helper T cells – produced by people who have received either of the two messenger RNA (mRNA) vaccines for COVID-19 caused by the original SARS-CoV-2 strain also will recognize the mutant variants of the coronavirus that are rapidly becoming the dominant types worldwide.
They also found that the same T cells may provide some protection from another member of the coronavirus family that is responsible for one type of the common cold.
The findings were reported April 6, 2021, in the Journal of Clinical Investigation.
CD4+ T cells get their “helper” nickname because they assist another type of immune cell, the B lymphocyte (B cell), in responding to surface proteins – antigens – on cells infected by invaders that include viruses such as SARS-CoV-2.
Activated by the CD4+ T cells, immature B cells become either plasma cells that produce antibodies to mark infected cells for disposal from the body or memory cells that “remember” the antigen’s biochemistry for a faster response to future infections.
In the case of SARS-CoV-2, the antigen is the protein making up the spikes that protrude from the surface of the virus. The mRNA vaccines – known by their manufacturer’s names, Pfizer-BioNTech and Moderna – provide genetic instructions to a vaccinated person’s immune system to recognize the spike protein and start production of antibodies against SARS-CoV-2.
CD4+ T cells also send out chemical messengers that attract another type of T cell – known as the CD8+ T cell (or “killer T cell”) – so that the virus-infected cells can be removed.
To conduct their helper T cell study, the researchers evaluated blood samples from 30 healthy health care workers and laboratory donors who had not previously tested positive for SARS-CoV-2 – both before and after two doses of a COVID-19 mRNA vaccine.
The participants, 12 women and 18 men, ranged in age from 20 to 59.
CD4+ T cells extracted from the blood samples were analyzed for their responses to various components (protein fragments known as peptides) from the original strain SARS-CoV-2 spike protein and three common cold coronaviruses.
The researchers discovered that vaccine recipients – as expected – had broad T cell responses to the original strain SARS-CoV-2 spike peptides.
“We identified 23 distinct T cell-targeted peptides, of which only four appear affected by the mutations that created the variant coronaviruses first seen in the United Kingdom and South Africa,” says study senior author Joel Blankson, M.D., Ph.D., professor of medicine at the Johns Hopkins University School of Medicine.
Blankson says this is important because previous studies showed that antibodies don’t recognize the SARS-CoV-2 variants as well as the CD4+ T cells.
“So the T cells may help prevent the variant viruses from causing severe COVID-19 disease even if antibodies don’t stop them from infecting a person,” he explains.
When the researchers looked at the vaccine-induced T cell response to the spike proteins of three common cold coronaviruses, they saw a three-fold increase for one, HCoV-NL63, but not the other two.
“Further studies are needed to determine why this occurred,” says Blankson. “We suspect that HCoV-NL63 may have more epitopes [peptides that elicit an immune response] in common with SARS-CoV-2 than the other common cold coronaviruses.”
In a recent and related study, Blankson and Johns Hopkins Medicine colleagues looked at blood from convalescent patients who had recovered from a SARS-CoV-2 infection and identified the unique receptors on memory CD4+ T cell that recognize the spike proteins of both the original strain of SARS-CoV-2 and four common cold coronaviruses.
Blankson says that characterizing these T cell receptors may be helpful in guiding development of future vaccines for a variety of coronaviruses.
The recent emergence of new SARS-CoV-2 variants of concern, including the B.1.1.7 variant in the UK, B.1.351 variant in South Africa, P.1 variant in Brazil and B.1.427 variant in California, USA, has important implications for future responses to the pandemic. Whereas the effects of mutations in the viral spike (S) protein on antibody binding and neutralization have been addressed in several reports, the impact of SARS-CoV-2 variant mutations on T cell reactivity remains poorly understood.
In this non-peer-reviewed preprint, Tarke et al. applied an integrated approach to assess T cell responses to SARS-CoV-2 variants from 11 COVID-19 convalescent individuals and 19 recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) vaccines.
Different methodologies were used to detect T cells with a range of functionalities and specific cytokine activity in response to overlapping peptide pools spanning the S protein of the original SARS-CoV-2 sequence and each of the corresponding variants.
Both CD4+ and CD8+ T cells from COVID-19 convalescent donors were found to recognize the ancestral reference strain and the variant proteome-wide sequences with similar efficiency. In mRNA vaccine recipients also, CD4+ and CD8+ T cell responses to the ancestral and variant peptide pools were similar, with the exception of the B.1.351 variant, for which mildly decreased T cell reactivity to S protein peptides was observed.
Analysis of defined T cell epitopes showed that 93% of CD4+ T cell epitopes and 97% of CD8+ T cell epitopes are conserved in the analysed variants. Single point mutations in the T cell epitopes were predicted to have no negative effect on HLA binding capacity, which provides a molecular basis for the marginal impact of the mutations on T cell responses in the study group.
Together, these findings suggest a negligible impact of the SARS-CoV-2 variant mutations on global CD4+ and CD8+ T cell responses in COVID-19 convalescent donors and COVID-19 mRNA vaccine recipients, and have important implications for the design of vaccines inducing broader immunity against variants of concern.
The use of overlapping peptide pools in this study does not exclude the possibility that mutations described in the variants could interfere with antigen processing, thereby affecting T cell activation and function. It remains to be determined whether T cell responses following infection with circulating variants can efficiently cross-recognize the ancestral sequence in approved vaccines.
reference link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044658/
More information: Bezawit A. Woldemeskel et al. SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63, Journal of Clinical Investigation (2021). DOI: 10.1172/JCI149335