Altered T-cell response in hemodialysis patients following third COVID-19 vaccine dose

The global impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the coronavirus disease 2019 (COVID-19) pandemic, has been immense, especially for the healthcare sector and economy. To date, the pandemic has claimed more than 6.5 million lives worldwide.

Several COVID-19 vaccines have received emergency use authorization (EUA) from global regulatory bodies like the United States Food and Drug Administration (FDA), with vaccination programs having commenced in most countries.

Study: A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile. Image Credit: pics five / Shutterstock.com

Background

Vaccination against COVID-19 vaccines has significantly reduced the severity of SARS-CoV-2 infection. COVID-19 vaccines based on the messenger ribonucleic acid (mRNA) technology elicit a robust humoral and cellular immune response, especially in their ability to recruit T helper (TH) and B-cells. However, mRNA vaccines induce a weak CD8+ T-cell response.

Initially, two mRNA vaccine doses were recommended; however, this vaccination regimen was revised to three doses to improve their effectiveness against SARS-CoV-2 variants of concern (VOCs). A longer interval between the first two COVID-19 vaccine doses has been shown to enhance humoral responses, as well as increase specific B-cell responses and maturation among low-risk populations. However, an increase in the interval did not have any significant effect impact on T-cell responses.

Patients at a mature stage of kidney disease and subjected to hemodialysis (HD) are susceptible to COVID-19. Previously, research has shown that this group exhibits a suboptimal response to the standard vaccination protocol for hepatitis B virus (HBV), diphtheria, and influenza immunizations.

A delayed immune response affecting B and T lymphocytes, dendritic cells, monocytes, and neutrophils has been observed due to uremia toxins and blood-membrane interactions during dialysis. Importantly, higher or multiple vaccine doses are effective strategies against influenza and HBV in this patient population.

Due to the high risk that HD patients will contract COVID-19 and experience severe disease, this group is considered to be a high priority for SARS-CoV-2 vaccination. Following vaccination against COVID-19, HD patients often exhibit reduced anti-SARS-CoV-2 antibody production as compared to the general population. In addition, an earlier decline, even after three doses of vaccines, has been observed.

About the study

In a recent study published on the bioRxiv* preprint server, scientists define the quantitative and qualitative trajectories of vaccine-induced antibody responses, such as B, CD4+, and CD8+ T-cells, against COVID-19 in HD patients who received three mRNA COVID-19 vaccine doses. These findings were compared to antigen-specific responses in the healthy control group.

Study findings

A third COVID-19 vaccine dose is crucial for HD patients to induce B-cell expansion and maturation equal to that of the control group. Previous high-dimensional functional assays have shown that TH responses in patients undergoing HD are phenotypically and functionally skewed; however, no changes in quantitative levels were observed in the current study. 

The cellular analysis findings are consistent with previous studies that have reported that multiple or higher vaccination dosage can counterbalance their low responses to immunization. When the time between the first two vaccine doses was increased in COVID-19-vaccinated individuals also subjected to HD treatment, a weaker humoral and cellular immune response occurred. Nevertheless, the third vaccine dose enhanced antibody levels in the HD cohort as compared to the control group.

In the HD group, reduced production of receptor binding domain (RBD)+ B-cells was observed after the first two COVID-19 vaccine doses. HD patients vaccinated against COVID-19 with mRNA vaccines exhibited a delay in the maturation of B-cells, along with immature and unswitched immunoglobulin M (IgM)+ and IgD+ RBD+B cells. Similar conditions were observed in kidney transplant recipients and dialysis patients due to chronic inflammation as a result of the presence of uremia toxins, as well as anomalies in innate and T-cell immunity.

Strong antigen-specific CD4+ T-cell responses were observed in HD patients vaccinated against COVID-19. However, a quantitative difference was found between HD and control groups. Receipt of a third dose of the COVID-19 vaccine was characterized by the regularization of the effector function profile as compared to controls.

Conclusions

The current study reports that a twelve-week interval between the first two COVID-19 vaccine doses was not beneficial for HD patients. A weak B-cell response was observed after the second vaccine dose in the HD cohort. Although the optimal vaccination regimen in this group has not been determined, a marginally longer interval was recommended for stronger humoral responses.

Many alterations in adaptive immunity were found to be induced by COVID-19 vaccination in HD patients. Therefore, more research is needed to elucidate the factors associated with this heterogeneity and determine the underlying mechanism responsible for this immune defect. Further research is also needed to understand how prior SARS-CoV-2 infection affects hybrid immunity in HD patients upon vaccination.

*Important notice

bioRxiv 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.