Woelfel Simon, Junker Daniel, Bergamin Irina, Meyer-Herbon Pamela, Stillhard Roman, Graf Nicole, Leinenkugel Georg, Dütschler Joel, König Marius, Kammerlander Livia, Häuptle Rahel, Zwyssig Sarah, Krieger Claudia, Truniger Samuel, Koller Seraina, Metzger-Peter Katline, Frei Nicola, Albrich Werner C, Friedrich Matthias, Bernsmeier Christine, Niess Jan Hendrik, Korte Wolfgang, Bürgi Justus J, Dulovic Alex, Schneiderhan-Marra Nicole, Semela David, Brand Stephan
Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland.
Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Faculty of Medicine, Ludwig Maximilian University (LMU), 80336 Munich, Germany.
Vaccines (Basel). 2024 Oct 31;12(11):1241. doi: 10.3390/vaccines12111241.
Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied.
We present the first evaluation of XBB.1.5 COVID-19 vaccine immunogenicity against the SARS-CoV-2 JN.1 variant in patients with CLD. Serum anti-receptor binding domain (RBD) IgG, neutralization, and saliva anti-RBD IgG and IgA against wild-type SARS-CoV-2 (WT) and the XBB.1.5, EG.5.1, BA.2.86, and JN.1 variants were quantified before and 2-4 weeks following a fourth dose of XBB.1.5 mRNA vaccines.
Vaccination boosted anti-RBD IgG and neutralization against all tested variants including JN.1 (each < 0.001). Following immunization, neutralization was lower against JN.1 compared to WT, XBB.1.5, and EG.5.1 ( < 0.001, < 0.001, and < 0.01, respectively). Vaccination reduced neutralization failure rates against BA.2.86 and JN.1 (each < 0.05). The evasion of vaccine-induced antibodies by the tested variants was low, indicated by the positive correlation between anti-RBD IgG and neutralization. At mucosal sites, vaccination boosted anti-RBD IgG (each < 0.01) but failed to induce infection-blocking IgA (each > 0.05).
XBB.1.5 vaccines protect CLD patients against recent SARS-CoV-2 variants, but developing vaccines with optimized mucosal immunogenicity is required to prevent SARS-CoV-2 transmission and recurrent seasonal COVID-19 outbreaks.
慢性肝病（CLD）患者的疫苗免疫原性受损，且感染重症 COVID-19 的风险更高。虽然推荐为易感个体接种针对变异株的 COVID-19 mRNA 疫苗，但尚未对其在 CLD 患者中的疗效进行研究。
我们首次评估了 XBB.1.5 COVID-19 疫苗对 CLD 患者中 SARS-CoV-2 JN.1 变异株的免疫原性。在接种第四剂 XBB.1.5 mRNA 疫苗前及接种后 2 - 4 周，对血清抗受体结合域（RBD）IgG、中和抗体，以及唾液抗 RBD IgG 和 IgA 针对野生型 SARS-CoV-2（WT）、XBB.1.5、EG.5.1、BA.2.86 和 JN.1 变异株进行定量检测。
接种疫苗可增强针对包括 JN.1 在内的所有测试变异株的抗 RBD IgG 和中和抗体（均 P < 0.001）。免疫后，与 WT、XBB.1.5 和 EG.5.1 相比，针对 JN.1 的中和抗体较低（分别为 P < 0.001、P < 0.001 和 P < 0.01）。接种疫苗降低了针对 BA.2.86 和 JN.1 的中和失败率（均 P < 0.05）。抗 RBD IgG 与中和抗体之间的正相关表明，测试变异株对疫苗诱导抗体的逃逸率较低。在黏膜部位，接种疫苗可增强抗 RBD IgG（均 P < 0.01），但未能诱导出感染阻断性 IgA（均 P > 0.05）。
XBB.1.5 疫苗可保护 CLD 患者抵御近期的 SARS-CoV-2 变异株，但需要研发具有优化黏膜免疫原性的疫苗，以预防 SARS-CoV-2 传播和季节性 COVID-19 复发疫情。
