Although some remarkable advances have been made in the detection, prevention of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) and treatment of coronavirus disease (COVID-19), the emergence of the recent Omicron variant has highlighted how much there is yet to learn regarding the immune responses of the virus.
The correlation between SARS-CoV-2 vaccine protectiveness and analysis of adaptive immune response to SARS-CoV-2 infection is still unclear. Moreover, vaccination has primarily focused on antibodies (Abs), and not much attention has been paid to T cells, which provide significant protection against severe diseases.
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Due to limited studies on the role of T cells in SARS-CoV-2 research, policies regarding long-term protection from the virus after Abs decline and against emerging variants are difficult to determine. Although the quantitative measurement of Abs is more convenient, scientists are assessing T cells in vaccine trials and other research.
Inclusion of both Abs and T cells in the assessment of adaptive immune responses during the beginning of the pandemic could also help to counter misinformation that leads to vaccine hesitancy as well as provide swift messaging. This gap was quite prominent in the initial results of the BNT162b2 vaccine trial in a population whose age ranges from 2 to 5 years which made it insufficient for it to receive emergency use authorization for this population.
Examination of T cell responses can also help in the evaluation of protective immunity, clinical diagnosis, and vaccine assessment. In addition, analysis of the broader adaptive immune responses can help evaluate why some patients are asymptomatic while others are severely ill.
Now, a group of prominent scientists and physicians are urging the FDA to include in its guidance to vaccine developers a recommendation for T-cell assessment in COVID-19 vaccine clinical trials to more comprehensively measure immune response. They write that it is critical to measure T-cell responses in addition to antibodies to evaluate vaccine efficacy better and make informed decisions regarding ongoing protection against current and future variants.
Improvement of information for the vulnerable population
Seven million immunocompromised people in the US struggle to protect themselves from infection. Information on T cell response can help to tailor vaccination schedules or use prophylactic and other measures for these populations. To combat COVID-19, all tools must be used, including T cell assessment, due to its disproportionate impact on some populations. Determination of the role of T cells in protective immunity will benefit the entire population, especially those most vulnerable to infection.
Strengthening of public health response and confidence
Protection can have two dimensions, protecting people from getting infected and preventing severe illness from infection. Both the Omicron and Delta variants have sown evasion of antibody responses. However, the emergence of the Omicron variant led to the analysis of T cell importance to balance the loss of Ab-mediated protection. Several studies have reported the preservation of vaccine-induced T-cell response against this variant that leads to continued vaccine efficacy.
Assessment of only the humoral aspect of the adaptive immune response cannot provide enough information on immunity. T cell responses have been reported to be more durable as compared to serum neutralizing Ab titers. Additionally, many studies have also suggested that Abs alone might not be sufficient to protect against severe disease.
Therefore, it can be concluded that the continuation of the pandemic has emphasized T cell response for protecting against variants that are capable of escaping neutralizing Ab response. Data on the broad immune response beyond Abs must be collected, especially for the vulnerable populations, to determine public health strategies and policies. Further research on the full range of adaptive responses is required to curb the current pandemic as well as future pandemics and epidemics. Reducing misinformation regarding COVID-19 that leads to vaccine hesitancy is also vital for providing adequate protection from the disease.
Consistent with this perspective, 70 investigators signed a letter to the FDA on April 21, 2022, encouraging the inclusion of T cell responses in addition to antibody titers for the evaluation of SARS-CoV-2 vaccines in humans.