CLEVER study for SARS-CoV-2 Ver 1.0
Research type
Research Study
Full title
CLinical EValuation of a simplE immunity Readout (CLEVER) study for SARS-CoV-2
IRAS ID
305040
Contact name
Maria A Oliver
Contact email
Sponsor organisation
INDOOR BIOTECHNOLOGIES LTD
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Research Summary
With the role out of the SARS-CoV-2 vaccination programme here in the UK well underway, questions around the efficacy and the longevity of these vaccines are beginning to be asked. The aim of vaccinations is to produce a robust, long lived immune response, thus preventing re-infection in the wider population. The production of antibodies is one way the body can fight viral infections. Additionally, long-term protection also comes from T-cells, which play a critical role in controlling and eradicating the virus. However, little is known about the longevity of the T-cell response generated from vaccinations. Therefore, our goal is to develop a novel T-cell test that will contribute to addressing some fundamental research questions such as if immunity will begin to wane after a defined time, and will differences in magnitude or longevity of these response be observed in vulnerable cohorts or those deemed to be more 'at risk' from infection within the wider population?
Historically, measuring T-cell immune responses to viruses has proved a more difficult task than measuring virus-specific antibodies as they are laborious and require complex technical know-how. Here, we propose using a novel system that is designed to overcome the technical hurdles and time constraints associated with traditional method y using a whole blood method.
We will stimulate T cells in the blood samples and measure the subsequent production of cytokines - proteins that form a crucial part of the immune system that aids with eradicating the virus. By involving at-risk groups, including people with HIV, immunocompromised people, and people with a low vaccine response, the project team aim to assess if T-cell immunity wanes faster in these groups of individuals than in the wider population.Summary of Results
1) Accurate assessment of T cell responses is critical for understanding the magnitude and longevity of immunity across patient cohorts, and against emerging variants. By establishing a simple, accurate and rapid whole blood test, natural and vaccine-induced SARS-CoV-2 immunity was determined. Cytokine release in whole blood stimulated with peptides specific for SARS-CoV-2 was measured in donors with previous PCR-confirmed infection, suspected infection or with no exposure history; and in donors pre- and post-vaccination. Longitudinal assessment of T cell responses following initial vaccination and booster vaccination was also conducted. Cytokines IL-2 and IFN-γ were highly elevated in PCR-confirmed donors compared to history negative controls, with median levels ~33-fold and ~48-fold higher, respectively. Statistical analysis showed IL-2 as the superior of the two biomarkers. Following vaccination, all donors demonstrated a positive IL-2 response. Median IL-2 levels increased ~32-fold from pre-vaccination to post-vaccination in uninfected individuals. Longitudinal assessment revealed T cell responses were stable up to 6 months post-vaccination. No significant differences in cytokine production were observed between stimulations with Wuhan, Delta or Omicron peptides.
2) The immunocompromised population is a heterogenous group of individuals who may respond differently to vaccinations depending on factors such as vaccine type, underlying disease, and concurrent drug administration. Thus, some may be better protected from COVID-19 disease by SARS-CoV-2 vaccinations than others. Our aim was to measure vaccine-induced immunity in several immunocompromised cohorts and to compare these to immunocompetent controls. In donors with no history of SARS-CoV-2 infection (78% of donors), cytokines IFN-γ and IL-2 were greatly reduced in renal transplant recipients compared to immunocompetent controls. A significant reduction in cytokine production was also seen in the anti-TNFα treated cohort. No significant difference in cytokine production was observed between the HIV positive cohort and immunocompetent controls. The level of SARS-CoV-2 spike specific IgG was significantly reduced in the renal transplant cohort compared to immunocompetent controls, with a median value of 134µg/ml in the transplant group versus 502µg/ml for the controls. No significant difference in IgG levels were observed for the other immunocompromised groups. Cytokine production and spike specific IgG levels in donors with previous COVID-19 (22% of donors) were comparable between all groups.
3) Immune responses in the immunocompetent group were measured 6-9 months post-initial blood donation. Those that had been infected with SARS-CoV-2 in between blood donations (almost 100% likelihood of being infected with Omicron due to prevalence of that variant at the time of infection) showed mostly stable T cell immune responses along with increased circulating antibody levels. No evidence of any correlation between initial immune response and subsequent infection was found. In those individuals who remined COVID free, both their T cell response and antibody levels showed some signs of waning, although a measurable response was detected in nearly all individuals.
4) Results from the capillary blood draw methods vs venous blood draw revealed that some cytokines are affected more than others. The background level of the cytokines shows more disparity than the SARS-CoV-2 stimulated samples. The TAP II method appears to be a more gentle, more reliable method of capillary blood draw as compared to the lancet method, which can lead to unspecific upregulation of certain T cell related cytokines. The TAP II method yields results more similar to the venous blood draw than the lancet does.REC name
Wales REC 6
REC reference
21/WA/0369
Date of REC Opinion
19 Nov 2021
REC opinion
Favourable Opinion