Introduction
The widespread use of COVID-19 mRNA vaccines marked a turning point during the 2020 coronavirus pandemic and saved millions of lives ever since.1 Until today, vaccines continue to protect from severe illness and long-term ailments associated with COVID-19 and, therefore, are crucial in controlling the burden of SARS-CoV-2 on healthcare systems and personal life quality.2,3 Anti-TNF-treated patients with inflammatory bowel disease (IBD) are at increased risk for SARS-CoV-2 infection due to impaired vaccine immunogenicity.4-6 To maintain high levels of immunoprotection, adapted COVID-19 vaccines are recommended for patients with IBD. However, many IBD patients rely on pre-existing immunity elicited by original vaccines or prior infections. We assessed if such immunity sufficiently combats highly immune-evasive SARS-CoV-2 variants causing the current summer 2024 COVID-19 wave.
Aims & Methods
Utilizing two longitudinal cohorts, we evaluated immunity against the SARS-CoV-2 variant 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). Neutralization and anti-receptor binding domain (RBD) IgG levels against wild-type SARS-CoV-2 and JN.1 were assessed using multiplex immunoassays. The primary outcome was wild-type and JN.1 neutralization following three doses of original mRNA vaccines, stratified by immunosuppressive therapy. Secondary outcomes were wild-type and JN.1 neutralization following third-dose breakthrough infection or a fourth dose of XBB.1.5-adapted mRNA vaccines.
Results
Following original vaccines, JN.1 neutralization was lower than wild-type neutralization in all study groups (healthy, anti-TNF, non-anti-TNF; each p < 0.001), and most individuals lacked JN.1 neutralization (healthy: 97.9%; anti-TNF: 98.3%; non-anti-TNF: 92.3%). Confounder-adjusted multivariable modeling strongly associated anti-TNF therapy with low levels of anti-JN.1-RBD IgG (fold-change 0.48 [95% CI 0.39-0.59]; Table 1). JN.1 neutralization was similar in patients with versus without breakthrough infection (anti-TNF, non-anti-TNF; each p > 0.05), and neutralization failure was 100% despite breakthrough infection. XBB.1.5-adapted vaccines enhanced JN.1 neutralization (p < 0.001) and reduced neutralization failure rates in IBD patients (94.4% pre-vaccination vs 44.4% post-vaccination; p = 0.003).
Table 1. Multivariable model with logarithmized levels of anti-RBD IgG against the JN.1 variant after three original vaccine doses as outcome in patients with IBD and healthy controls. Exponentiated fold-changes and bootstrapped 95% CIs were exponentiated to show fold-changes of antibody concentration. Data are based on serum samples collected two to 16 weeks after vaccination.
Variable
| n/N
| Fold-change
| 95% confidence interval
|
Anti-TNF therapy
| 58/143
| 0.48
| 0.39-0.59
|
Non-anti-TNF therapy
| 38/143
| 0.95
| 0.76-1.21
|
Previous SARS-CoV-2 infection
| 17/143
| 0.87
| 0.65-1.20
|
Time between third-dose vaccination and sampling (per month)
| 143/143
| 0.78
| 0.67-0.89
|
Age (per decade)
| 143/143
| 0.97
| 0.90-1.04
|
Active smoking
| 26/143
| 0.80
| 0.63-0.97
|
Time between second- and third-dose vaccination (per month)
| 143/143
| 1.00
| 0.93-1.08
|
Vaccination with mRNA-1273 (vs BNT162b2)
| 27/143
| 1.18
| 0.87-1.49
|
Conclusion
Only variant-adapted vaccines protect against emerging SARS-CoV-2 variants. IBD patients and healthy individuals without recent vaccination lack protection against JN.1 and its subvariant KP.3.1.1, which contributes to current COVID-19 surges. Vaccination campaigns must be intensified to guarantee sufficient immunoprotection in patients with IBD and healthy individuals.
References
1. Watson OJ, et al. Global impact of the first year of COVID-19 vaccination: a mathematical modelling study. The Lancet Infectious Diseases 22, 1293–1302 (2022).
2. Lin DY, et al. Durability of XBB.1.5 Vaccines against omicron subvariants. N Engl J Med (2024) doi:10.1056/NEJMc2402779.
3. Lundberg-Morris L, et al. Covid-19 vaccine effectiveness against post-covid-19 condition among 589722 individuals in Sweden: population based cohort study. BMJ (2023) doi:10.1136/bmj-2023-076990.
4. Liu Z, et al. Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study. The Lancet Gastroenterology & Hepatology 8, 145–156 (2023).
5. Woelfel S, et al. Systemic and T cell‐associated responses to SARS‐CoV‐2 immunisation in gut inflammation (STAR SIGN study): effects of biologics on vaccination efficacy of the third dose of mRNA vaccines against SARS‐CoV‐2. Aliment Pharmacol Ther 57, 103–116 (2023).
6. Woelfel S, et al. STAR SIGN study: Evaluation of COVID-19 vaccine efficacy against the SARS-CoV-2 variants BQ.1.1 and XBB.1.5 in patients with inflammatory bowel disease. Alimentary Pharmacology & Therapeutics 58, 678–691 (2023).
Disclosure
SB received speaker’s honoraria from Abbvie, Falk Foundation, Ferring, Janssen, Lilly, MSD, Takeda, UCB, and Vifor and participated in advisory boards of Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Pfizer, Pierre Fabre, Roche, Takeda, and UCB. SB has received an educational grant from Takeda. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. WCA received funding from Swiss National Science Foundation (33IC30_201300), Cantonal Hospital St. Gallen, OM Pharma, FUNGINOS, Gilead, received payment for lectures and presentations by Pfizer, GSK, MSD, Gilead, paid to his institution, received payment for travel to meetings from Pfizer, GSK, Gilead, paid to his institution, and participated in the advisory boards of MSD, Sanofi, Pfizer, GSK, OM Pharma, Moderna, Aurovir Pharma, and Janssen. ST participated in the advisory boards of Takeda, Janssen, BMS, and Medinova. BM has received speaking or traveling fees and/or served on an advisory board with BMS, Abbvie, Takeda, Falk, iQONE, Amgen, MSD, Jansen, Gilead, and has received unrestricted research grants from MSD, BMS and Nestle.
