Standardizable assay detects T cell response to SARS-CoV-2 infection

Researchers in the United Kingdom have developed a high-throughput, standardizable assay that accurately detects the response of T cells to infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). This is the agent that causes coronavirus disease (COVID-19) in 2019.

Andrew Godkin and colleagues at Cardiff University say such tests are essential to understanding the role of T cell responses in long-term immunity to SARS-CoV-2, especially among immunocompromised individuals. I am.

“Although the exact nature of effective immunity has not yet been fully defined, the SARS-CoV-2 specific T cell response is an important feature of the immune response and forms an important correlation of defense against COVID-19. It’s likely to happen, “the team wrote.

The ability to rapidly identify the presence of SARS-CoV-2 specific T cell responses helps determine the adaptive immune status of previously infected or vaccinated individuals and detect unexpected and previous infections. ..

Researchers say the inclusion of such data in herd immunity studies and personalized immunological certificates can have widespread implications for blockade policies.

This information may help improve the assessment of vaccine efficacy in the community and highlight the possibility of needing boosters in the event of weakened immunity.

The preprinted version of the research treatise is medRxiv* While the server, article is being peer reviewed.

“We need to understand effective COVID-19 immunity at the population level.”

Researchers are trying to understand how the adaptive immune response generated after SARS-CoV-2 infection or vaccination is protected from future infections.

“To control future epidemics and identify individuals at risk, we need to understand the exact components of COVID-19 immunity that are effective at the population level,” says Godkin and colleagues.

Recent studies have shown that in almost all cases of SARS-CoV-2 infection, a virus-specific T cell response occurs and persists for at least 6 months.

Traditionally, viral antigen-specific T cell responses have been evaluated using flow cytometry or ELISpot-based readout. However, neither approach is suitable for high-throughput processing and cannot be standardized between laboratories.

In addition, currently available assays that detect SARS-CoV-2-specific cell-mediated immune responses measure only the cytokine interferon-gamma (IFNg) released by. T cellsDespite the fact that other type 1 T-helper (TH1) cellular cytokines may be a better indicator of antiviral response.

To overcome these limitations, existing whole blood-based immunoassays can be adapted to measure virus-specific T cell responses in a high-throughput, standardizable way.

The SARS-CoV-2 specific T cell response identifies previous asymptomatic infections. IFN-g (A) and IL-2 (B) releases in response to the SARS-CoV-2 S- / NP- / M-binding peptide pool were measured in 156 evaluable participants and previously COVID- 19 Subdivided into vaccinated individuals (gray, n = 52), previous COVID-19 positive PCR test results (blue, n = 12-15), or previously positive called “unknown / inexperienced” Persons without COVID-19 testing (orange, n = 88). Statistical analysis shows the results of the Kruskal-Wallis test with Dan correction for multiple comparisons (**** P <0.0001). (C) The SARS-CoV-2 specific IL-2 + T cell response was correlated with the IFN-g + response subdivided by participant status. Anti-SARS-CoV-2 RBD IgG antibody titers correlate with the magnitude of IFN-g + T cell response (D) and IL-2 + T cell response (E) in identified asymptomatic participants It was highlighted. The result of regression analysis is shown. The sensitivity and specificity readings for IFN-g (F) and IL-2 (G) were defined by the receiver operating characteristic curve. The area under the curve (AUC) and associated P value are shown.

Monitoring the immune response of the elderly and immunosuppressed states is especially important

Monitoring the immune response to SARS-CoV-2 in the elderly and immunosuppressed individuals is especially important given the significantly higher mortality rates observed in these groups.

The incidence of cancer is also increasing among the elderly, and reduced adaptive immune response and age-related inflammation contribute to the progression of the disease.

“In fact, the early signs are that cancer patients, especially those receiving aggressive treatment such as chemotherapy, can initiate an antibody-T cell response to the Pfizer-Bio NTech SARS-CoV-2 mRNA vaccine. It suggests that the sex is significantly lower, “said Godkin and the team.

What did the researchers do?

Researchers have adapted and optimized a widely used, high-throughput, whole-blood assay for TH1 types associated with previous SARS-CoV-2 infection and / or vaccination of 156 healthy donors (TH1 types). IFNg / IL-2) Cell-mediated immune response was determined. And 67 patients with solid organ cancer.

Participants were recruited between February and April 2021 and stratified based on previous self-reports of SARS-CoV-2 infection and / or laboratory evidence. Participants who reported no positive reaction in the past were defined as “unknown / inexperienced”.

Blood samples were taken immediately prior to the first dose and 3-6 weeks after the first dose to measure the immune response generated by COVID-19 vaccination.

All immunized individuals received either Pfizer-BioNTech’s BNT162b2 vaccine or AstraZeneca’s ChAdOx1 nCoV-19 vaccine.

What did the study find?

Significant differences in IFNg + and IL-2 + SARS-CoV-2 specific T cell responses among healthy donors have been observed between vaccinated or previously infected individuals and unknown / inexperienced individuals. It was.

Measurement of IL-2 produced in response to SARS-CoV-2-derived T cells antigen Was a predictable diagnostic assay with 96.0% sensitivity and 93.9% specificity.

Measurement of IFNg + SARS-CoV-2 specific T cell response was also useful in identifying asymptomatic infected individuals.

A single dose of vaccine-induced IFNg and / or IL-2 SARS-CoV-2 specific T cell response was given in 28 (96.6%) of 29 healthy donors, but 56 cancer patients. Only 27 of them (48.2%)..

“These data further support the recent demand for cancer patients to prioritize booster immune vaccines and long-term immunological monitoring,” the team wrote.

What did the authors conclude?

Researchers have found that this cost-effective, high-throughput, standardizable test that allows accurate and equivalent assessment of SARS-CoV-2 specific T cell responses is susceptible to extensive herd immunity tests. It states.

“We have demonstrated the high sensitivity and specificity of this assay to identify or rule out previous SARS-CoV-2 infections and / or successful COVID-19 vaccinations,” said Godkin and colleagues.

“From now on, it is essential to use such tests to understand the exact contribution of T cell responses to SARS-CoV-2 infection, especially for long-term immunity among immunocompromised individuals.” They conclude.

*Important Notices

medRxiv Is published as a preliminary scientific report that has not been peer-reviewed and is therefore considered definitive, guides clinical practice / health-related behaviors, and is treated as established information. It’s not a thing.