An exploratory study of T-cell and antibody responses after COVID-19 mRNA vaccination

Recent COVID-19 investigations have found that up to half of immunocompromised individuals struggle to produce antibodies after receiving their severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations.

This is significant as it can show inefficacies in vaccinations for the most vulnerable population to this disease. The lack of solid evidence has given rise to an exploratory study that investigates whether T-cells that respond to the spike protein are present in serial samples before and after the administration of each dose of messenger-RNA (mRNA) vaccinations in healthy immunocompetent patients compared to immunocompromised patients.

Only 15% of immunocompromised transplant patients receiving chronic immunosuppression produce an antibody response after the first dose of their mRNA SARS-CoV-2 vaccination. This inconsistency in antibody development in immunocompromised individuals after SARS-CoV-2 vaccinations signifies the importance of cellular immunity assessments for this population type.

Although the percentage of antibody response does increase to 54% after the second dose for immunocompromised patients, this level is still far lower than their healthy immunocompetent counterparts.

An exploratory study by researchers based in the United States and primarily within the University of Pittsburgh investigated the response of T-cells to the spike (S) antigenic sequence as well as the less conserved S1 and conserved S2 components before and after mRNA vaccinations were administered. Twenty immunocompetent samples and 7 samples from vaccinated immunocompromised patients were observed. The research is posted online on the medRxiv* preprint server prior to peer review.

A few measuring points for the researchers included measuring the immunoglobulin, IgG antibodies to the receptor-binding domain of S1 as well as the anti-S IgG antibodies; this was undertaken with the aim of characterizing the T-cell and IgG response to the spike antigenic sequences before and after the vaccine doses.

Immunocompromised responses to COVID-19 vaccines

Compared with healthy people, chronically immunosuppressed transplant patients have a lower immune response to COVID-19 infections. Due to being more vulnerable, they are more susceptible to experiencing severe infections of the coronavirus. This can include having decreased spike-antigen-reactive T-cells as well as decreased IgG antibodies to the receptor-binding domain of the spike protein.

The spike S antigenic sequence consists of the S1 and S2 components. The less conserved N-terminal S1 component contains the receptor-binding domain (RBD), while the other component is known as the conserved C-terminal S2 sequence.

When cellular immunity assessments are undertaken, such as in T-cell assays, the CD154 marker can be used to assess viral antigen-specific T-cells, as this marker is co-expressed with interferon-gamma upon an S antigen stimulation from the COVID-19 infection.

These same researchers have also found an increase in myeloid suppressor cell numbers after COVID-19 infections, which might impair T-cell responses to S antigens and suppress T-cell responses.

Exploratory Study Findings

When observing the effects on the healthy subjects, the S1 reactive CD8 T-cells were the only T-cell subset that increased significantly after the second dose of the vaccine in healthy immunocompetent individuals when compared to the pre-vaccination levels.

Additionally, there was an increase in anti-RBD and anti-spike IgG antibodies after each dose was administered. The findings suggest that the second vaccination dose is important for effective antibody responses.

The results of the vaccinated immunocompromised subjects illustrated inconsistencies with the antibody and overall T-cell response to the COVID-19 infection. Anti-RBD and anti-spike IgG antibodies were found in 3 of 7 and 4 of 7 patient samples, respectively, which signifies the number of samples that did not show the presence of these antibodies. However, the patient samples which did not produce these antibodies did have higher numbers of S-reactive CD4 or CD8 T-cells, which may be due to having previous exposure to the infection.

While this exploratory study has shown the importance of cellular immunity assessments with the analysis of the T-cell and antibody responses to the COVID-19 infection for immunocompromised patients, it is not representative of the population due to the small sample size and differing underlying conditions included.

Due to the fact that the study did not observe pre-vaccination levels in the immunocompromised samples, no conclusions can be drawn on the basis of actual evidence but can be theorized.

However, the study does provide insight into the inconsistencies in the immune response after vaccinations for those who are immunosuppressed as well as a comparison to healthy and immunocompetent samples, which can help give rise to similar studies in order to meet the health need for this vulnerable group more effectively.

Important Notice

A pre-print version of the exploratory study is available on the medRxiv server, while the article undergoes peer review. medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Marzia Khan

Written by

Marzia Khan

Marzia Khan is a lover of scientific research and innovation. She immerses herself in literature and novel therapeutics which she does through her position on the Royal Free Ethical Review Board. Marzia has a MSc in Nanotechnology and Regenerative Medicine as well as a BSc in Biomedical Sciences. She is currently working in the NHS and is engaging in a scientific innovation program.


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