XBB.1.5适应性新冠mRNA疫苗而非既往奥密克戎变种感染可增强炎症性肠病患者对SARS-CoV-2 JN.1变种的中和作用。

XBB.1.5-Adapted COVID-19 mRNA Vaccines but Not Infections With Previous Omicron Variants Boost Neutralisation Against the SARS-CoV-2 JN.1 Variant in Patients With Inflammatory Bowel Disease.

作者信息

Woelfel Simon, Dütschler Joel, Junker Daniel, König Marius, Graf Nicole, Krieger Claudia, Truniger Samuel, Oikonomou Vasileios, Leinenkugel Georg, Koller Seraina, Metzger-Peter Katline, Wyss Jacqueline, Krupka Niklas, Frei Nicola, Albrich Werner C, Friedrich Matthias, Niess Jan Hendrik, Schneiderhan-Marra Nicole, Dulovic Alex, Misselwitz Benjamin, Korte Wolfgang, Bürgi Justus J, Brand Stephan

机构信息

Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.

Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Faculty of Medicine, Ludwig Maximilian University of Munich, Munich, Germany.

出版信息

Aliment Pharmacol Ther. 2025 Jan;61(2):299-312. doi: 10.1111/apt.18349. Epub 2024 Oct 29.

DOI:10.1111/apt.18349

PMID:39468971

Abstract

BACKGROUND

Variant-adapted COVID-19 vaccines are recommended for patients with inflammatory bowel disease (IBD). However, many patients rely on pre-existing immunity by original vaccines or prior infections.

AIM

To assess whether such immunity sufficiently combats the highly immune-evasive SARS-CoV-2 JN.1 variant.

METHODS

Utilising two longitudinal cohorts, we evaluated immunity against JN.1 induced by original vaccines (IBD: n = 98; healthy: n = 48), omicron breakthrough infection (IBD: n = 55; healthy: n = 57) or XBB.1.5-adapted vaccines (IBD: n = 18). Neutralisation and anti-receptor-binding domain (RBD) IgG levels against wild-type SARS-CoV-2 and JN.1 were assessed using multiplex immunoassays. Study outcomes were wild-type and JN.1 neutralisation following three doses of original mRNA vaccines, stratified by immunosuppressive therapy (primary outcome), and JN.1 neutralisation following third-dose breakthrough infection or a fourth dose of XBB.1.5-adapted mRNA vaccines (secondary outcomes).

RESULTS

Following original vaccines, JN.1 neutralisation was lower than wild-type neutralisation in all study groups (healthy, anti-TNF and non-anti-TNF; each p < 0.001); most individuals lacked JN.1 neutralisation (healthy: 97.9%; anti-TNF: 98.3% and non-anti-TNF: 92.3%). Confounder-adjusted multivariable modelling strongly associated anti-TNF therapy with low levels of anti-JN.1-RBD IgG (fold-change 0.48 [95% CI 0.39-0.59]). JN.1 neutralisation was similar in patients with or without breakthrough infection (anti-TNF, non-anti-TNF; each p > 0.05); neutralisation failure was 100% despite breakthrough infection. XBB.1.5-adapted vaccines enhanced JN.1 neutralisation (p < 0.001) and reduced neutralisation failure rates in patients with IBD (94.4% pre-vaccination vs. 44.4% post-vaccination; p = 0.003).

CONCLUSIONS

Only variant-adapted vaccines protect against emerging SARS-CoV-2 variants. Patients with IBD and healthy individuals without recent vaccination may lack protection against the JN.1 subvariant KP.3 which causes current COVID-19 surges.

摘要

背景

对于炎症性肠病（IBD）患者，推荐接种变异株适配的新型冠状病毒肺炎（COVID-19）疫苗。然而，许多患者依赖于原始疫苗或既往感染产生的预先存在的免疫力。

目的

评估这种免疫力是否足以对抗具有高度免疫逃逸能力的严重急性呼吸综合征冠状病毒2（SARS-CoV-2） JN.1变异株。

方法

我们利用两个纵向队列，评估了原始疫苗（IBD组：n = 98；健康组：n = 48）、奥密克戎突破性感染（IBD组：n = 55；健康组：n = 57）或XBB.1.5适配疫苗（IBD组：n = 18）诱导的针对JN.1的免疫力。使用多重免疫测定法评估针对野生型SARS-CoV-2和JN.1的中和作用及抗受体结合域（RBD）IgG水平。研究结果包括三剂原始mRNA疫苗接种后野生型和JN.1的中和作用（按免疫抑制治疗分层，为主要结局），以及第三剂突破性感染或第四剂XBB.1.5适配mRNA疫苗接种后JN.1的中和作用（为次要结局）。

结果

接种原始疫苗后，所有研究组（健康组、抗TNF组和非抗TNF组）中JN.1的中和作用均低于野生型中和作用（各p < 0.001）；大多数个体缺乏对JN.1的中和作用（健康组：97.9%；抗TNF组：98.3%；非抗TNF组：92.3%）。经混杂因素调整的多变量模型显示，抗TNF治疗与低水平的抗JN.1-RBD IgG密切相关（变化倍数为0.48 [95%置信区间0.39 - 0.59]）。有或无突破性感染的患者中JN.1的中和作用相似（抗TNF组、非抗TNF组；各p > 0.05）；尽管有突破性感染，中和失败率仍为100%。XBB.1.5适配疫苗增强了JN.1的中和作用（p < 0.001），并降低了IBD患者的中和失败率（接种疫苗前为94.4%，接种疫苗后为44.4%；p = 0.003）。