Changes in T-cell responses in hemodialysis patients after the third dose of COVID-19 vaccine

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

Several COVID-19 vaccines have obtained Emergency Use Authorizations (EUAs) from global regulatory bodies such as the U.S. Food and Drug Administration (FDA), and most countries have initiated vaccination programs.

study: Administration of a third SARS-CoV-2 mRNA vaccine to persons undergoing hemodialysis overcomes the B cell defect but induces a skewed CD4+ T cell profile. Image Credit: Photo 5/Shutterstock.com

Background

Vaccination against the COVID-19 vaccine significantly reduced the severity of SARS-CoV-2 infection. COVID-19 vaccines based on messenger ribonucleic acid (mRNA) technology induce potent humoral and cellular immune responses, particularly in their ability to recruit T helpers (TH) and B cells. However, mRNA vaccines induce weak CD8+. T cells response.

Initially, two doses of mRNA vaccine were recommended. However, this vaccination regimen was revised to 3 doses to improve efficacy against SARS-CoV-2 variants (VOCs) of concern. Longer intervals between doses of the first two COVID-19 vaccines have been shown to enhance the humoral response and promote the maturation of specific her B-cell responses and low-risk populations. However, increasing the interval did not significantly affect T cell responses.

Patients in the mature stage of kidney disease and undergoing hemodialysis (HD) are more susceptible to COVID-19. Previous studies have shown that this group has a suboptimal response to standard vaccination protocols for her hepatitis B virus (HBV), diphtheria, and influenza vaccinations.

Due to uremic toxins and blood membrane interactions during dialysis, delayed immune responses have been observed affecting B and T lymphocytes, dendritic cells, monocytes, and neutrophils. Importantly, higher or multiple vaccinations are effective strategies against influenza and HBV in this patient population.

This group is considered a high priority for SARS-CoV-2 vaccination, as HD patients are at high risk of severe illness from COVID-19. After vaccination against COVID-19, HD patients often show reduced anti-SARS-CoV-2 antibody production compared to the general population. Moreover, an early decline is observed even after her 3 doses of the vaccine.

About research

In a recent study published in bioRxiv* Using a preprint server, scientists can quantitatively and qualitatively assess vaccine-induced antibody responses, including B, CD4+, and CD8+ T cells, to COVID-19 in HD patients who received three doses of the COVID-19 mRNA vaccine. defines a trajectory. These findings are antigen– Specific response in healthy controls.

Survey results

The third dose of COVID-19 vaccine is critical for HD patients to induce B cell expansion and maturation comparable to controls. Previous hyperdimensional functional assays have shown that her TH responses in patients undergoing HD are phenotypically and functionally skewed. However, no quantitative level changes were observed in the current study.

The cellular analysis results are consistent with previous studies that reported that multiple or more vaccinations offset poor responses to vaccination. Prolonging the interval between her first two vaccinations in a COVID-19-vaccinated, HD-treated individual attenuated humoral and cellular immune responses. Nevertheless, the third vaccine dose enhanced antibody levels in the HD cohort compared with the control group.

A decrease in the production of receptor-binding domain (RBD)+ B cells was observed in the HD group after the first two doses of COVID-19 vaccine. HD patients vaccinated with mRNA vaccines against COVID-19 showed delayed maturation of B cells, as did immature, unswitched immunoglobulin M (IgM)+ and IgD+ RBD+ B cells. Similar conditions have been observed in kidney transplant recipients and dialysis patients, with chronic inflammation as a result of the presence of uremic toxins, and abnormalities in innate and T-cell immunity.

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

Conclusion

The current study reports that a 12-week interval between the first two COVID-19 vaccinations was not beneficial for HD patients. A weak B-cell response was observed after the second dose of vaccine in the HD cohort. The optimal vaccination regimen in this group has not been determined, but slightly longer intervals were recommended due to stronger humoral responses.

Many changes in adaptive immunity have been found to be induced by COVID-19 vaccination in HD patients. Therefore, further studies are needed to elucidate the factors associated with this heterogeneity and identify the underlying mechanisms responsible for this immune defect. Further research is also needed to understand how previous SARS-CoV-2 infection affects hybrid immunity in HD patients upon vaccination.

*Important Notices

Bio Rxiv We publish a non-peer-reviewed, preliminary scientific report and should not be viewed as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.