Protective Effect of Vaccine Doses and Antibody Titers Against SARS-CoV-2 Infection in Kidney Transplant Recipients.

Patients undergoing kidney transplantation have a poor response to vaccination and a higher risk of disease progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of vaccine doses and antibody titer tests against the mutant variant in these patients remains unclear. We retrospectively analyzed the risk of SARS-CoV-2 infection in a single medical center according to vaccine doses and immune responses before the outbreak. Among 622 kidney transplant patients, there were 77 patients without vaccination, 26 with one dose, 74 with two doses, 357 with three, and 88 with four doses. The vaccination status and infection rate proportion were similar to the general population. Patients undergoing more than three vaccinations had a lower risk of infection (odds ratio = 0.6527, 95% CI = 0.4324-0.9937) and hospitalization (odds ratio = 0.3161, 95% CI = 0.1311-0.7464). Antibody and cellular responses were measured in 181 patients after vaccination. Anti-spike protein antibody titer of more than 1,689.3 BAU/mL is protective against SARS-CoV-2 infection (odds ratio = 0.4136, 95% CI = 0.1800-0.9043). A cellular response by interferon-γ release assay was not correlated with the disease (odds ratio = 1.001, 95% CI = 0.9995-1.002). In conclusion, despite mutant strain, more than three doses of the first-generation vaccine and high antibody titers provided better protection against the omicron variant for a kidney transplant recipient.

Humeral and cellular immune responses to SARS-CoV-2 vaccination in patients on peritoneal dialysis.

BACKGROUND: Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD). METHOD: We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody ≥0.8 U/mL and interferon-γ ≥ 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison. RESULT: PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients. CONCLUSION: Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination.

Immunogenicity and safety of two-dose SARS-CoV-2 vaccination via different platforms in kidney transplantation recipients.

After kidney transplantation, patients exhibit a poor response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, the efficacy and adverse effects of vaccines based on different platforms in these patients remain unclear. We prospectively analyzed both anti-spike protein antibody and cellular responses 1 month after the first and second doses of SARS-CoV-2 vaccines in 171 kidney transplant patients. Four vaccines, including one viral vector (ChAdOx1 nCov-19, n = 30), two mRNA (mRNA1273, n = 81 and BNT162b2, n = 38), and one protein subunit (MVC-COV1901, n = 22) vaccines were administered. Among the four vaccines, mRNA1273 elicited the strongest humoral response and induced the highest interferon-γ levels in patients with a positive cellular response against the spike protein. Antiproliferative agents were negatively associated with both the antibody and cellular responses. A transient elevation in creatinine levels was noted in approximately half of the patients after the first dose of mRNA1273 or ChadOx1, and only one of them presented with borderline cellular rejection without definite causality to vaccination. In conclusion, mRNA1273 had better immunogenicity than the other vaccines. Further, renal function needs to be carefully monitored after vaccination, and vaccination strategies should be tailored according to the transplant status and vaccine characteristics.

The bZip Transcription Factor VdMRTF1 is a Negative Regulator of Melanin Biosynthesis and Virulence in Verticillium dahliae.

The ascomycete fungus Verticillium dahliae infects over 400 plant species and causes serious losses of economically important crops, such as cotton and tomato, and also of woody plants, such as smoke tree, maple, and olive. Melanized long-term survival structures known as microsclerotia play crucial roles in the disease cycle of V. dahliae, enabling this soilborne fungus to survive for years in the soil in the absence of a host. Previously, we identified VdMRTF1 (microsclerotia-related transcription factor) encoding a bZip transcription factor which is downregulated during microsclerotial development in V. dahliae. In the present study, we showed that VdMRTF1 negatively controls melanin production and virulence by genetic, biological, and transcriptomic analyses. The mutant strain lacking VdMRTF1 (ΔVdMRTF1) exhibited increased melanin biosynthesis and the defect also promoted microsclerotial development and sensitivity to Ca2+. In comparison with the wild-type strain, the ΔVdMRTF1 strain showed a significant enhancement in virulence and displayed an increased capacity to eliminate reactive oxygen species in planta. Furthermore, analyses of transcriptomic profiles between the ΔVdMRTF1 and wild-type strains indicated that VdMRTF1 regulates the differential expression of genes associated with melanin biosynthesis, tyrosine metabolism, hydrogen peroxide catabolic processes, and oxidoreductase activity in V. dahliae. Taken together, these data show that VdMRTF1 is a negative transcriptional regulator of melanin biosynthesis, microsclerotia formation, and virulence in V. dahliae. IMPORTANCE Verticillium wilt is difficult to manage because the pathogen colonizes the plant xylem tissue and produces melanized microsclerotia which survive for more than 10 years in soil without a host. The molecular mechanisms underlying microsclerotia formation are of great importance to control the disease. Here, we provide evidence that a bZip transcription factor, VdMRTF1, plays important roles in melanin biosynthesis, microsclerotial development, resistance to elevated Ca2+ levels, and fungal virulence of V. dahliae. The findings extend and deepen our understanding of the complexities of melanin biosynthesis, microsclerotia formation, and virulence that are regulated by bZip transcription factors in V. dahliae.