Anti-vaccine antibodies against measles, rubella, parotitis and hepatitis B in children with inflammatory bowel disease and healthy controls

Abstract

BACKGROUND

Patients with inflammatory bowel diseases (IBD) often miss the scheduled vaccines and have a higher risk of infection susceptibility, including vaccine-prevented diseases.

AIM

To evaluate the vaccine coverage and levels of the post-vaccine antibodies against measles, mumps, rubella, and hepatitis B in children with IBD.

METHODS

Total 98 patients: 46 females (47.2%) and 52 males (52.8%) with IBD (Crohn’s disease-75% and ulcerative colitis-25%) with disease onset age-11.0 (6.0; 14.0) years whom clinical data, vaccination status and levels of the post-vaccination antibodies (IgG) for measles, rubella, mumps, hepatitis B, measured with ELISA were prospectively evaluated. The control group consisted of 88 healthy peers from the biobank data.

RESULTS

Patients with IBD had lower levels of measles, rubella, and hepatitis B, except mumps, compared to controls. Incomplete vaccination/non-protective titer of the antibodies against measles, mumps rubella, and hepatitis B had 33 (33.7%)/52.3%, 21 (21.4%)/50.4%, 26 (25.8)/25.6% and 26 (25.8%)/55.2%, respectively. Patients with incomplete vaccination had a lower age at the diagnosis for all vaccines. The age of the IBD diagnosis ≤ 6 years was the predictor of incomplete vaccination for measles [odds ratio (OR) = 4.6, P = 0.001], mumps (OR = 5.0, P = 0.001), rubella (OR = 5.4, P = 0.0005) and hepatitis B (OR = 5.4, P = 0.0005) and corticosteroid treatment for measles (OR = 2.2, P = 0.074) and mumps (OR = 3.0, P = 0.047) vaccines. Incomplete vaccination was the predictor of non-protective titer of antibodies against rubella (OR = 6.8, 95%CI: 2.3-19.9, P = 0.0002)/mumps (OR = 7.0, 95%CI: 2.4-20.8; P = 0.0002).

CONCLUSION

Patients with IBD had low vaccine coverage and lower levels of anti-vaccine antibodies against measles, rubella, and hepatitis B. Nearly half of the IBD patients require revaccination.

Key Words: Inflammatory bowel diseases; Vaccine; Measles; Mumps; Rubella; Hepatitis B; Antibodies; Anti-vaccine antibodies; Vaccine coverage; Children

Core Tip: Improving vaccination, engaging the trust of parents and physicians in vaccination, and its safety and efficacy in children with immune-mediated diseases could decrease the infection risks. This study showed the vaccine coverage, the predictors of incomplete vaccination, and non-protective levels of post-vaccine antibodies. The younger onset of the disease onset disrupts the following scheduled vaccination. Avoiding corticosteroid treatment, regular assessment of anti-vaccine antibodies, and encouragement of vaccination are the main goals for managing patients with inflammatory bowel diseases.

INTRODUCTION

Immune-compromised children are at a substantially higher risk of vaccine-preventable infections and associated complications compared to their healthy counterparts[1–4]. Within this group, children diagnosed with inflammatory bowel disease (IBD)—encompassing Crohn’s disease (CD) and ulcerative colitis (UC)—require especially vigilant monitoring of infection risk. Nonetheless, vaccination coverage in this population remains inadequate. Notably, many of the severe infections that lead to hospitalization could be prevented through routine immunization.

According to a recent study, the annual incidence of these infections is 2.2% (1 in 45) among patients receiving a combination of anti-tumor necrosis factor (TNF) and non-biological immunosuppressive therapy, and the infection risk increases with age. These infections impose a high burden of morbidity and carry a 3.9% mortality rate at three months[5]. In contrast, vedolizumab has been associated with a lower incidence of serious infections[6].

Guidelines recommend that patients undergo comprehensive screening for hepatitis A, B, and C viruses, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, rubella, and human papillomavirus (HPV) at the time of IBD diagnosis[7–10]. In cases where children have low IgG antibody titers from prior vaccinations, revaccination is advised to achieve protective levels before the start of immunosuppressive therapy. These children may also benefit from additional vaccines, including pneumococcal, influenza, and HPV[7,8].

Professional organizations, including the European Crohn’s and Colitis Organization, the American Gastroenterological Society, the Institute, and the Canadian Association of Gastroenterology, have consistently emphasized the safety and significance of vaccination for IBD patients[8,9]. However, immunization rates remain suboptimal among pediatric and adolescent IBD patients. Key barriers include limited awareness among healthcare providers, insufficient coordination between primary care physicians and specialists, and heightened concerns from patients and parents regarding potential side effects[10,11].

Vaccination has proven to be an effective strategy to reduce both the frequency and severity of infections. It may also indirectly lower the risk of IBD flares and improve overall disease outcomes. Updated international guidelines (2021) underscore the pivotal role of immunization in IBD management, advocating routine vaccination against tetanus, diphtheria, and polio, alongside periodic review of vaccination status. Furthermore, five key vaccines are particularly recommended for all IBD patients: Varicella, HPV, annual inactivated influenza, pneumococcal conjugate vaccine, and hepatitis B for seronegative individuals[12,13].

While live vaccines are contraindicated for patients undergoing immunosuppressive therapy, all other age-appropriate vaccines should be administered[8]. Recent studies indicate that vaccination adherence among children with IBD is markedly lower than in the general population. Moreover, caregivers of children with IBD often harbor greater concerns about vaccine safety and effectiveness than those whose children do not have IBD[14]. Despite immunosuppressive therapy, many children with IBD still lack the recommended immunizations[15].

Immune response to vaccination

Children with IBD generally show adequate immune responses to inactivated vaccines, even when immunosuppressive therapy is administered[16]. However, certain challenges persist. Studies evaluating seroprotection against hepatitis B in pediatric patients with IBD indicate that while most develop protective antibody levels following the standard three-dose schedule, individuals receiving immunosuppressive treatments—such as corticosteroids or anti-TNF agents—demonstrate lower response rates[11,15]. These observations underscore the importance of early vaccination before initiating immunosuppressive therapy and suggest the potential need for additional booster doses to maintain protective immunity.

Immunogenicity for other vaccines, including those against pneumococcal and influenza infections, has also been reported as sufficient for most patients[7,8,16]. Nonetheless, immunosuppressants used in IBD management can influence vaccine efficacy. Patients on aminosalicylates or thiopurines generally retain normal vaccine responses, whereas anti-TNF agents, especially in combination regimens, may reduce immunogenicity[17-19]. In contrast, immunosuppressive therapy does not appear to affect antibody concentrations for measles, mumps, and rubella[20]. Vedolizumab, targeting α4β7 integrin, likewise has not been shown to adversely impact responses to hepatitis B or influenza vaccines[21]. Ustekinumab (an IL-12/IL-23 inhibitor) and tofacitinib (a JAK inhibitor) may also affect vaccine response, although further research is needed in IBD populations[22,23]. These findings highlight the need for routine serological testing to identify gaps in immunity and prompt revaccination where necessary[8,14].

MATERIALS AND METHODS

In the prospective cohort study analysis, we included 98 patients with IBD. The study was conducted in the pediatric department of gastroenterology of Saint-Petersburg State Pediatric Medical University from January 2021 to April 2023.

Eligibility criteria

Study inclusion criteria: Patients with CD and UC who wished to participate in the study.

Non-inclusion criteria: Patients without data about vaccination against measles, rubella, mumps, and hepatitis B.

Assessments and outcomes

From every patient, the following information was extracted: (1) Demography: Sex, disease onset age, and study inclusion age; (2) Clinical: Type of IBD, disease activity – PCDAI[24] and PUCAI[25] at different time points (IBD onset and study inclusion); (3) Data about vaccination: Type of vaccine, age of the vaccination, the overall number of vaccines against measles, rubella, mumps, and hepatitis B, the vaccine coverage to age according to the National vaccination schedule, information about the patients, who continued vaccination[26]. Information about the scheduled vaccination against MMR and hepatitis B, the JIA course, and treatment was obtained from the patient's charts; (4) The levels of post-vaccination antibodies (IgG) for measles, rubella, mumps, and hepatitis B, measured with ELISA. IgG concentrations were determined from calibration curves constructed using Dynex Technologies Inc. software (United States). The protective level of antibodies was established by the criteria specified in the manufacturer's instructions: For measles IgG 0.18 IU/mL (coefficient of variation, CV, 8%; analytical sensitivity 0.07 30 IU/mL), for antibodies to rubella 10 IU/mL (8%; 2 IU/mL), for hepatitis B (anti-HBs antibodies) 10 mmol/LE/mL (8%; 2 mIU/mL). The minimal protective level of IgG against mumps was established with a positivity coefficient > 1.0. To detect measles, rubella, mumps, and hepatitis B 1 antibodies, we used the commercial kit created by Vector-Best JSC, Russia, and IBL International GMBH (Germany). The measurement of anti-vaccine antibodies was done in the diagnostic laboratory of the Research Clinical Center of Infectious Disease; and (5) The data about anti-vaccine titers in healthy peers (n = 88) was extracted from the biobank of the Research Clinical Center of Infectious Disease, using the same method.

Ethics

The local Ethics Committee of the Saint-Petersburg State Pediatric Medical University approved the trial protocol (protocol number 9/02 from 11/02/2019). All procedures performed in studies involving human participants were by the ethical standards of institutional and/or research committees and with the 1975 Declaration of Helsinki, as revised in 2013. Written consent from the parents and patients older than 14 years has been obtained according to the declaration of Helsinki.

Statistical analysis

The sample size was not calculated initially. Statistical analysis was performed with the software STATISTICA, version 10.0 (StatSoft Inc., United States) and MedCalc (MedCalc Software, Belgium). All continuous variables were checked by the Kolmogorov–Smirnov test, with no normal distribution identified. We used a nonparametric statistics test due to the absence of the normal distribution of the quantitative variables.

Quantitative variables were presented with median and percentiles (25-75) and absolute frequencies and percentages for categorical variables. For comparison, the categorical variables Pearson's χ² test or Fisher's exact test in case of expected frequencies < 5 was used, and a comparison of two quantitative variables was carried out using the Mann-Whitney test. Pearson’s and Spearman's correlation tests were performed to assess the association between the studied parameters. Differences were considered statistically significant if the P value was less than 0.05.

RESULTS

Patients’ demography

The studied population consists of 46 females (47.2%) and 52 males (52.8%) with the age of inclusion 14 (11.0; 16.0) years and onset age 11.0 (6.0; 14.0) years. The main type of IBD was CD (75%), and the remaining patients had UC (25%). The majority of the patients had chronic disease course (90%). Extra-intestinal features were found in 15% of the patients: Uveitis (4.2%), arthritis (2.1%), primary sclerosing cholangitis (7.4%), skin diseases: Erythema nodosum 1.1% and pyoderma gangrenosum 1.1%. At the study inclusion, the CD activity was 2.5 times lower than in onset and 14 times lower in UC patients compared to the disease onset. Systemic corticosteroids were received by 56.1% of the patients, conventional DMARDs received 92.8% at onset and 42.3% at study inclusion with and without biologics. The majority of the patients received biologic treatment (TNF-α inhibitors 91.4%), and 13.2% required to switch the biologic at least one time. The modification of the biological treatment (increasing the dose or shortening the time between the drug administration) required 23.6% of the patients (Table 1).

Table 1 Demographic characteristics of patients with inflammatory bowel diseases, included in the study, n (%)/median (25^th-75^th percentiles).

Parameter	n = 98
Sex, females	46 (47.2)
Age of the inclusion in the study	14 (11.0-16.0)
Age of the disease onset	11 (6.0-14.0)
Diagnosis
Ulcerative collitis	25 (25.0)
Crohn’s disease	73 (75.0)
IBD course
Acute (< 6 months since the onset)	10 (10)
Chronic persistent (no remission episodes > 6 months duration during the relevant treatment)	29 (30)
Chronic relapsed (remission > 6 months)	60 (60)
Extra-intestinal features	15 (15.3)
IBD activity at the diagnoses
CD, PCDAI, points	37 (25-45)
UC, PUCAI, points	35 (33-45)
IBD activity at the study inclusion
CD, PCDAI, points	15 (0.0-30.0)
UC, PUCAI, points	2.5 (0.0-10.0)
Biologic treatment before the study	76 (77.5)
Infliximab	48 (70.6)
Adalimumab	21(30.8)
Vedolizumab	7 (10.3)
Number of biologics before the study inclusion
one	59 (86.8)
two	6 (8.8)
three	3 (4.4)
Current treatment with TNF-α inhibitors	41 (61.2)
Increased dose or decreased intervals between TNF-α inhibitors	23 (42.6)
Duration of treatment with TNF-α inhibitors, (months)	3.5 (1.2-22.0)
Systemic corticosteroids (> 1 mg/kg) at onset	56 (60.1)
Duration of systemic corticosteroids, months	2.0 (1.0-3.0)
Conventional DMARDS
Azathyaprine	64 (65.3)
Methotrexate	22 (22.5)
6-mercaptopurine	10 (10.2)
Tacrolimus	2 (2.0)
Topical anti-inflammatory drugs	39 (39.8)
Surgical treatment, related to IBD	12 (12.4)
Conventional DMARDs
At onset	91 (92.8)
At study inclusion	51 (42.3)

IBD: Inflammatory bowel disease; CD: Crohn's disease; UC: Ulcerative colitis; PCDAI: Pediatric Crohn's disease activity index; PUCAI: Pediatric ulcerative colitis activity index; TNF-α: Tumor necrosis factor alpha; DMARDs: Disease-modifying anti-rheumatic drugs.

Vaccination coverage and post-vaccine immunity

Incomplete vaccination to the age against measles, mumps rubella, and hepatitis B had 33 (33.7%), 21 (21.4%), 26 (25.8), and 26 (25.8%) compared to healthy peers (100% for all vaccines; P = 0.00001), respectively (Table 2). Only 14.3% of patients continued vaccination after the onset of the IBD.

Table 2 Post-vaccine immunity in inflammatory bowel diseases patients and healthy peers, n (%)/median (25^th-75^th percentiles).

Parameter	IBD (n = 98)	Healthy (n = 88)	P value
Antibodies against measles, IgG, (IU/mL)	0.15 (0.0-0.35)	0.5 (0.0-0.9)	0.00005
Complete vaccination against measles1	65 (66.3)	88 (100)	0.00001
Patients with a protective level of antibodies against measles	41/86 (47.7)	57 (58.2)	0.018
Antibodies against mumps, IgG, (IU/mL)	2.8 (0.9-5.0)	3.4 (1.2-7.2)	0.555
Complete vaccination against mumps1	21 (21.4)	88 (100)	0.00001
Patients with a protective level of antibodies against mumps	64/88 (49.6)	65 (50.4)	0.765
Antibodies against rubella, (IU/mL)	32 (0.0-52.0)	200 (110.7-200)	0.0000001
Complete vaccination against rubella1	25/97 (25.8)	88 (100)	0.00001
Patients with protective levels of antibodies against rubella	64/86 (74.4)	60/67 (89.6)	0.018
Antibodies against hepatitis B, (IU/mL)	0 (0.0-30.0)	120.9 (9.4-373.6)	0.0000001
Complete vaccination against hepatitis B1	72/97 (74.2)	88 (100)	0.00001
Patients with protective levels of antibodies against hepatitis B	39/87 (44.8)	65 (73.9)	0.0001

¹According to the National vaccination schedule to the age.

IBD: Inflammatory bowel disease.

Patients with incomplete vaccination had a lower age at the diagnosis for all vaccines: 7.0 (4.0-12.0) vs 13.0 (9.0; 5.0) years for measles (P = 0.0009); 6.0 (4.0- 12.0) vs. 12.0 (8.0-15.0) years for mumps (P = 0.001), 6.0 (4.0-12.0) vs. 12.0 (8.0-14.5) years for rubella (P = 0.0006), and 6.0 (4.0-12.0) vs 12.0 (8.0-14.5) years for hepatitis B (P = 0.0006). So, the age of the IBD diagnosis ≤ 6 years was the predictor of incomplete vaccination for all vaccines: Measles [60% vs 24.7%, odds ratio (OR) = 4.6, 95%CI: 1.8-12.0, P = 0.001], mumps (44.0% vs 13.7%, OR = 5.0, 95%CI: 1.8-14.0, P = 0.001), rubella (52% vs 16.7%, OR = 5.4, 95%CI: 2.0-14.7, P = 0.0005) and hepatitis B (52% vs 16.7%, OR = 5.4, 95%CI: 2.0-14.7, P = 0.0005).

Treatment with corticosteroids was a predictor of incomplete measles (41.1% vs 23.8%, OR = 2.2, 95%CI: 0.9-5.4, P = 0.074) and mumps (28.6% vs 11.9%, OR = 3.0, 95%CI: 1.0-8.9, P = 0.047) vaccination. The absence of concomitant diseases was associated with the risk of incomplete measles vaccination (56.3% vs 81.5%, OR = 3.4, 95%CI: 1.3-8.8, P = 0.008). The requirement to switch biologic was associated with incomplete vaccination against hepatitis B (60% vs 11.8%, OR = 5.1, 95%CI: 1.2-21.7, P = 0.0460). Incomplete vaccination against rubella was the predictor of non-protective titer of antibodies against rubella (17.3% vs 54.2%; OR = 6.8, 95%CI: 2.3-19.9, P = 0.0002), as well as incomplete vaccination against mumps was associated with non-protective level of the anti-mumps antibodies (40% vs 82.4%; OR = 7.0, 95%CI: 2.4-20.8; P = 0.0002). Incomplete vaccination against measles and hepatitis B was not associated with lower levels of antibodies or risk of having non-protective antibody levels.

No associations between the completeness of the vaccination against all the abovementioned infections and markers of the disease activity (PCDAI and PUCAI) were found.

Patients with IBD had lower levels of measles, rubella, and hepatitis B compared to healthy peers. The difference between anti-mumps antibodies was not significant.

The protective titer of the antibodies against measles was detected in 41/86 (47.7%) of the IBD patients and 57 (58.2%) of the healthy peers (P = 0.018). Patients with non-protective titer had higher PUCAI at the study inclusion 0 (0-0) vs 17.5 (7.5-30) points (P = 0.021), lower frequency of concomitant diseases (61.4% vs 80.5%, P = 0.053).

The protective titer of the antibodies against mumps was 64/88 (49.6%) of the IBD patients and 65 (50.4%) of the healthy peers (P = 0.765). Patients with non-protective antibodies against mumps had a younger age of the diagnosis 8.0 (4.0-13.5) vs 11.0 (7.0-14.5) years (P = 0.077), lower frequency of concomitant diseases (54.2% vs 76.2%, P = 0.045) compared to patients with protective titer of the antibodies.

The protective titer of the antibodies against rubella had 64/86 (74.4%) of the IBD patients and 60/67 (89.7%) healthy peers (P = 0.018). Patients with the non-protective level of antibodies against rubella had a younger age of the diagnosis 7.5 (4.0-13.0) vs 12.0 (0.0-14.5) years (P = 0.019) similar to patients with a non-protective titer of the antibodies against mumps and higher part of the patients experienced three biologics (20.0% vs 0%, P = 0.038).

The protective titer of the antibodies against hepatitis B was 39/87 (44.8%) of the IBD patients and 65 (73.97%) of the healthy peers (P = 0.0001). Patients with the non-protective titer of antibodies against hepatitis B had a longer duration of treatment with biological drugs - 6.5 (2.5-16.0) vs 3.0 (0.0-8.0) months (P = 0.036).

Correlation analysis revealed the negative association between anti-measles IgG titer and several previous biologics (r = -0.34, P = 0.047), PUCAI (r = -0.74, P = 0.023), positive association between anti-rubella IG titer and age of inclusion (r = 0.41, P = 0.013), negative association between titer of antibodies against hepatitis B and age of study inclusion (r = -0.45, P = 0.007) and duration of the treatment with biologics (r = -0.35, P = 0.040).

DISCUSSION

In our study, 21.4%-33.7% of the IBD patients missed the scheduled vaccination. The early onset age of the disease (≤ 6 years) leads to the omitting of the following scheduled vaccination. Disease activity and treatment with corticosteroids associated with non-protective levels of post-vaccine antibodies. The protective titer of post-vaccine antibodies against measles, mumps, and hepatitis B was less than half of the patients with IBD. The better situation regards protective levels of anti-rubella antibodies – nearly ¾ of the IBD patients have protective ones.

Recent investigations provide valuable insights into the immunological profiles of patients with IBD. In the work by Ford et al[10], serological evidence of immunity to several pathogens was examined, revealing that only 38.3% (23/60) of individuals were immune to Hepatitis B, 66.7% (36/54) to measles, 51.9% (28/54) to rubella, and 41.9% (26/62) to varicella zoster virus (VZV). Notably, 47.8% (33/69) of participants had already received additional vaccinations before their specialized clinic review, whereas 92.8% (64/69) were vaccinated in the subsequent 12 months[27].

These findings mirror previously published data concerning the evaluation of immunization status in IBD[8,28], with American clinicians reporting that only 63% of gastroenterologists assess vaccination records at the time of an IBD diagnosis. This assessment tends to focus chiefly on influenza (78%), hepatitis B (84%), and varicella (82%), while under 55.5% review the status of other vaccines[28].

Despite evidence of prior vaccinations, relatively low serologically confirmed immunity to hepatitis B virus (HBV), measles-mumps-rubella (MMR), VZV is frequently observed in these patients[29-31]. Such diminished response may stem from immunosuppressive therapy, the underlying disease pathophysiology, or inadequate timing of post-vaccination serologic assessment.

Both insufficient immune activation immediately following immunization and waning antibody titers over time could explain these lower-than-expected levels of immune markers[28-30]. Additionally, a meta-analysis of 13 studies with 1688 participants demonstrated that only around three in five IBD patients (61%, 95%CI: 53–69) developed a measurable immune response to the HBV vaccine[29]. Factors correlating positively with vaccine response included younger age and vaccination during disease remission[29]. Although fewer data are available concerning responses to VZV and MMR, a reduced immunogenic response has also been documented for influenza and pneumococcal vaccines in IBD cohorts[9,29,30].

Findings from another study underscore additional barriers to optimal immunization in this population. The majority of children followed for IBD were Caucasian males, with CD (68%) requiring immunosuppression. Families in the IBD group expressed significantly higher concern about vaccine safety (40% vs 16%, P = 0.03) and effectiveness (34% vs 12%, P < 0.01) compared with families of children without IBD. Alarmingly, 36% worried that vaccinations might exacerbate IBD symptoms (vs 10% in the non-IBD group, P < 0.01). Furthermore, many of these children were missing key vaccines—most notably influenza and HPV—and among those on biologic therapy, 96% had not received the recommended PPSV23 booster.

Collectively, these studies highlight the multifaceted obstacles to achieving optimal vaccine uptake and immunogenicity in children with IBD. Additional large-scale, longitudinal investigations are warranted to determine the best timing and strategies for vaccination, particularly under varying disease activity states and treatment regimens. Equally important are targeted educational initiatives aimed at healthcare providers, patients, and caregivers, which can help dispel misconceptions about vaccine safety and efficacy, ultimately improving immunization coverage and health outcomes in this vulnerable population.

Patients with IBD who receive immunosuppressive therapy, especially in combination regimens, face an elevated risk of opportunistic infections. Factors such as malnutrition, obesity, coexisting illnesses, active disease states, and older age further amplify this vulnerability[8]. Accordingly, these findings emphasize the crucial importance of prompt and comprehensive immunization strategies to reduce infection rates and improve overall patient outcomes[12,14].

In pediatric IBD populations, suboptimal vaccination rates are frequently attributed to insufficient coordination between primary care providers and specialists, compounded by parents’ safety concerns. To address these shortcomings, there is a need for evidence-based counseling directed at families and educational initiatives for healthcare professionals, aiming to increase vaccine uptake in this high-risk group. Previous online surveys of parents with children affected by rheumatic and gastrointestinal diseases have highlighted multiple barriers to vaccination, including limited access to accurate, detailed information and insufficient opportunities to discuss immunization with providers—both of which contribute to vaccine hesitancy[15].

Integrating vaccination guidance into routine specialist consultations may help alleviate these communication gaps. Nonetheless, a multifaceted approach is required to overcome ongoing barriers, encompassing stronger inter-professional collaboration, meaningful engagement of families in decision-making, and consistent messaging about the safety and efficacy of immunizations for children with IBD[27].

If a child is found to be non-immune after starting immunosuppressive therapy, it may be necessary to delay vaccination until the immunosuppression can be tapered or discontinued under medical supervision. This reality underscores the significance of proactive vaccination planning for pediatric patients anticipating such treatments[8,14,29-31].

From a gastroenterologist's perspective, diligent attention to recommended vaccine schedules for IBD patients and proactive coordination with the child immunization regimen remain paramount. Ideally, any overdue or booster doses should be identified and administered either at the point of initial IBD diagnosis or during key transitions of care[8].

According to our data, the number of patients with non-protective titers of anti-vaccine antibodies is two times higher than the number of patients with omitted vaccination. Nearly half of the patients in our cohort are required to be vaccinated or revaccinated. Disease activity and early onset age lead to incomplete vaccination, but incomplete vaccination is only one factor that decreases the antibodies' survival. Vaccination in children with IBD is a crucial component of preventive medicine, reducing the risk of infectious complications. Modern studies confirm the safety and efficacy of inactivated vaccines for IBD patients, though an individualized approach is essential, particularly for those undergoing immunosuppressive therapy. Further research is needed to optimize guidelines and improve awareness among healthcare professionals and parents.

In Russia, vaccination coverage among patients with immune-mediated diseases remains insufficient. While relatively high vaccination rates are observed in children with immune-mediated conditions due to the early onset of these diseases—most vaccines in the national schedule are administered in the first year of life—this trend sharply declines after diagnosis, with only 1 in 10 patients continuing their vaccination course. Additionally, it is not yet routine practice to assess antibody levels against vaccine-preventable diseases before initiating immunosuppressive therapy, a critical step that is often overlooked. Parents are not adequately informed about the importance of this evaluation, leading to missed opportunities for timely immunization[32,33]. Regular educational initiatives for healthcare professionals are essential to improve their understanding of vaccination in immunocompromised patients and to develop strategies for optimizing immunization practices. These efforts should also address the communication gap with parents, emphasizing the safety and necessity of vaccines in children with immune-mediated diseases. Tailored educational programs for both medical specialists and families can foster greater trust in vaccines and help improve vaccination rates in this vulnerable population.

The main limitations of this study are related to the small sample size, missing data, high heterogeneity of the studied population, different treatment approaches and time since disease onset, and study inclusion. The small sample size and diverse range of the treatment make it impossible to identify the exact role of the specific treatment on the anti-vaccine antibody level. Single-center design and study, which was carried out in one country with our local vaccines and national-specific vaccination schedule, decrease the applicability and may lack statistical power, and the results may not be generalizable to broader populations. Lack of adjustment for potential confounding variables due to the small sample size and absence of the data about the time since the last vaccination to assessment of the antibodies, no data about the socioeconomic status, and nutritional status decrease could skew the results and interpretations. The cross-sectional nature of the antibody assessment and the absence of the dynamic control of the antibodies do not allow us to find the factors influencing the antibodies' maintenance and do not allow us to find the individual time for the revaccination and diminish the clinical significance of the study results. All these limitations could influence the study results and may introduce biases. A more comprehensive analysis that accounts for these confounders would provide more robust and reliable findings.

CONCLUSION

Patients with IBD had low vaccine coverage and lower levels of anti-vaccine antibodies against measles, rubella, and hepatitis B. According to the serological data, nearly half of IBD patients require revaccination. Incomplete vaccination and non-protective levels of post-vaccination antibodies for measles, rubella, mumps, and hepatitis B were associated with early onset of IBD (≤ 6 years). High disease activity and corticosteroid treatment disrupt the protective levels of post-vaccine antibodies. The routine measurement of the main anti-vaccine antibodies should be implemented in the daily practice of pediatric gastroenterologists as well as evidence-based revaccination engagement. The following studies defying the predictors of incomplete vaccination and non-protective levels of anti-vaccine antibodies are needed as well as efforts to improve personalized vaccination in children with IBD.