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In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Longitudinal profiling of antigen receptor gene repertoire dynamics in kidney transplant recipients after multiple
Antonios Mingos1,2, Nikolaos Pechlivanis1, Georgios Karakatsoulis1
1Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece.
Abstract:
Kidney transplant recipients (KTRs) exhibit impaired immune responses to vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, remaining vulnerable to severe coronavirus disease 2019 (COVID-19) even after multiple vaccine doses. We hypothesized that repeated SARS-CoV-2 vaccinations in KTRs might promote remodeling of the adaptive immune repertoire. In order to address this hypothesis and gain insight into adaptive immune dynamics in this population, we employed next-generation sequencing (NGS) to determine longitudinal alterations in immunoglobulin (IG) and T cell receptor (TR) gene repertoires following multiple mRNA vaccinations and functional experiments to assess lymphocyte signaling capacity. TR gene repertoire analysis revealed increased diversity and reduced clonality after booster immunizations, indicative of substantial repertoire renewal. Although the relative frequency of SARS-CoV-2-specific TR clonotypes remained stable over time, significant shifts in TRBV gene usage reflected dynamic reshaping of the TR clonal architecture. Parallel IG gene repertoire profiling demonstrated increased diversity and limited oligoclonal expansions after booster mRNA vaccination. These changes were accompanied by elevated levels of somatic hypermutation in IG clonotypes similar to published SARS-CoV-2-specific clonotypes, suggestive of more efficient humoral responses following repeated antigenic exposure. Phospho-specific flow cytometry analysis revealed initially diminished B cell receptor signaling, which was restored following multiple immunizations, consistent with reversal of B cell anergy status. Altogether, our findings support the notion that repeated SARS-CoV-2 vaccinations drive the remodeling of cellular and humoral immune landscapes in KTRs. These results underscore the importance of tailored vaccination strategies to optimize immune protection in immunocompromised individuals.
Insights
Repeated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations in kidney transplant recipients (KTRs) remodel adaptive immune repertoires. Booster immunizations enhance immune cell diversity and function, improving responses in this vulnerable group.
Area of Science:
- Immunology
- Transplantation Science
- Vaccinology
Background:
- Kidney transplant recipients (KTRs) have weakened immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, increasing COVID-19 risk.
- The impact of repeated SARS-CoV-2 vaccination on adaptive immunity in KTRs remains unclear.
Purpose of the Study:
- To investigate longitudinal changes in immunoglobulin (IG) and T cell receptor (TR) gene repertoires following multiple SARS-CoV-2 mRNA vaccinations in KTRs.
- To assess functional lymphocyte signaling capacity after repeated vaccination in KTRs.
Main Methods:
- Employed next-generation sequencing (NGS) for IG and TR gene repertoire analysis.
- Utilized functional experiments, including phospho-specific flow cytometry, to evaluate lymphocyte signaling.
- Analyzed longitudinal alterations in immune repertoires after multiple mRNA vaccinations.
Main Results:
- Booster immunizations increased TR gene repertoire diversity and reduced clonality, indicating renewal.
- Significant shifts in TRBV gene usage and stable SARS-CoV-2-specific TR clonotype frequency were observed.
- IG gene profiling showed increased diversity and limited oligoclonal expansions post-boost.
- Elevated somatic hypermutation in IG clonotypes suggested improved humoral responses.
- B cell receptor signaling, initially diminished, was restored after multiple immunizations, reversing anergy.
Conclusions:
- Repeated SARS-CoV-2 vaccinations significantly remodel cellular and humoral immune landscapes in KTRs.
- These findings highlight the potential for tailored vaccination strategies to enhance immune protection in immunocompromised individuals.
- The study supports the benefit of booster immunizations for improving adaptive immune responses in KTRs.
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