Post-vaccination immunity against hepatitis B in children with Down syndrome

Relevance. An urgent task of modern medicine is to assess the effectiveness of the immune response to hepatitis B vaccination in children with Down syndrome. Studies show that most children with Down syndrome do not develop sufficient levels of protective antibodies after standard hepatitis B vaccination. Assessing the effectiveness of the immune response will allow for the development of personalized vaccination programs for children with Down syndrome.
Objective: to assess the effectiveness of the immune response to hepatitis B vaccination in children with Down syndrome by studying the concentration of specific antibodies in their blood serum and comparing the results with their vaccination status.
Materials and methods. A cross-sectional cohort study was performed with the participation of 102 children with Down syndrome aged from 1 to 17 years. The concentration of IgG antibody titers to hepatitis B was analyzed, based on age and vaccination status (full, partial vaccination, no vaccination).
Results. 73 (71,6 %) children had completed hepatitis B vaccination among all the subjects. The concentration of hepatitis B antibodies in children with Down syndrome decreases significantly with age, reaching a titer below 10 mIU/ml in most adolescents over 12 years of age. In children with complete vaccination in the 1–5 years group, the geometric mean of antibody titers was 24.5 mIU/ml, in the 6–11 years group, it was 26.7 mIU/ml, while in children aged 12–17 years, the antibody titers were below the protective threshold, with a geometric mean of 2.13 mIU/ml, indicating the need for further revaccination under certain conditions. Correlation analysis revealed a negative relationship between age and antibody levels (r = −0.3205, p = 0.0057). Children with Down syndrome do not have an epidemiological advantage for hepatitis B in “indicator” groups
Conclusion. Among children with Down syndrome aged 12 years and older who have received a full course of hepatitis B vaccination, there is a very high percentage of those who do not have a p rotective antibody titer. It is recommended to develop a personalized approach to revaccination and monitor post-vaccination antibodies to maintain an adequate level of protection.

1. Centers for Disease Control and Prevention (CDC). Ten great public health achievements — United States, 1900–1999. MMWR Morb Mortal Wkly Rep. 1999; 48 (12): 241–243.

2. Alkema L., Chao F., You D., Pedersen J., Sawyer C.C. National, regional, and global sex ratios of infant, child, and under-5 mortality and identification of countries with outlying ratios: a systematic assessment. Lancet Glob Health. 2014; 2 (9): e521– e530. https://doi.org/10.1016/s2214-109x(14)70280-3.

3. Familiar-Macedo D., Dias H.G., Carvalho F.R., et al. Serological investigation of vaccine-induced antibodies for measles, rubella, and yellow fever viruses in children vertically exposed to Zika virus or with down syndrome. Front Pediatr. 2023; 11: 1250059. https://doi.org/10.3389/fped.2023.1250059.

4. Romano’ L., Zanetti A.R. Hepatitis B Vaccination: A Historical Overview with a Focus on the Italian Achievements. Viruses. 2022; 14 (7): 1515. https://doi.org/10.3390/v14071515.

5. Chirkova A.Yu., Novopoltseva E.G., Tarasova A.A., et al. Retrospective epidemiological analysis of the incidence of Down syndrome in the Nizhny Novgorod region. Treatment and Prevention. 2024; 14 (2): 22–29. (In Russ.)

6. Danopoulos S., Deutsch G.H., Dumortier C., Mariani T.J., Al Alam D. Lung disease manifestations in Down syndrome. Am J Physiol Lung Cell Mol Physiol. 2021; 321 (5): L892–L899. https://doi.org/10.1152/ajplung.00434.2020.

7. Ram G., Chinen J. Infections and immunodeficiency in Down syndrome. Clin Exp Immunol. 2011; 164 (1): 9–16. https://doi.org/10.1111/j.1365-2249.2011.04335.x.

8. Cruz N.V., Mahmoud S.A., Chen H., et al. Follow-up study of immune defects in patients with dysmorphic disorders. Ann Allergy Asthma Immunol. 2009; 102 (5): 426–431. https://doi.org/10.1016/s1081-1206(10)60516-9.

9. Joshi A.Y., Abraham R.S., Snyder M.R., Boyce T.G. Immune evaluation and vaccine responses in Down syndrome: evidence of immunodeficiency? Vaccine. 2011; 29 (31): 5040–5046. https://doi.org/10.1016/j.vaccine.2011.04.060.

10. Chirkova A.Yu., Novopoltseva E.G., Tarasova A.A., et al. Approaches to the diagnosis of immunodeficiency conditions in children with Down syndrome. Allergology and Immunology in Paediatrics. 2025; (3): 56–65. (In Russ.) https://doi.org/10.53529/2500-1175-2025-3-56-65.

11. Huggard D., Doherty D.G., Molloy E.J. Immune Dysregulation in Children With Down Syndrome. Front Pediatr. 2020; 8: 73. https://doi.org/10.3389/fped.2020.00073.

12. Eijsvoogel N.B., Hollegien M.I., Bok V.L.A, et al. Declining antibody levels after hepatitis B vaccination in Down syndrome: A need for booster vaccination? J Med Virol. 2017; 89: 1682–1685. https://doi.org/10.1002/jmv.24813.

13. Okoli G.N., Grossman Moon A., Harper D.M. Hepatitis B vaccination initiation and vaccination series completion: An in-depth systematic evidence review, with meta-analysis of associations with individual socioeconomic and health-related factors. Vaccine. 2025; 55 (19): 127051. https://doi.org/10.1016/j.vaccine.2025.127051.

14. Fireizen S.M., Finkelstein A., Benisti L., Tenenbaum A. Vaccination decision-making in children with intellectual and developmental disabilities — it’s a matter of trust. Vaccine. 2026; 77: 128382. https://doi.org/10.1016/j.vaccine.2026.128382.

15. Kaplina S.P., Kharit S.M., Skripchenko N.V. Osobennosti immunologicheskogo statusa detey s sindromom Dauna. Epidemiologiya i vaktsinoprofilaktika. 2012; (3): 61–70. (In Russ.)

16. Dinleyici M., Carman K.B., Kilic O., Laciner Gurlevik S., Yarar C., Dinleyici E.C. The immunization status of children with chronic neurological disease and serological assessment of vaccine-preventable diseases. Hum Vaccin Immunother. 2018; 14 (8): 1970–1976. https://doi.org/10.1080/21645515.2018.1460986.

17. Pandolfi E., Carloni E., Marino M.G., Ciofi degli Atti M.L., Gesualdo F., Romano M., Giannattasio A., Guarino A., Carloni R., Borgia P., et al. Immunization coverage and timeliness of vaccination in Italian children with chronic diseases. Vaccine. 2012; 30 (34): 5172–5178. https://doi.org/10.1016/j.vaccine.2011.02.099.

18. Kaplina S.P., Kharit S.M., Skripchenko N.V. Vaccination in Russia in modern conditions. Rossiyskiy vestnik perinatologii i pediatrii. 2018; 63 (1): 5–13. (In Russ.) https://doi.org/10.21508/1027-4065-2018-63-1-5-13.

19. Valentini D., Marcellini V., Bianchi S., et al. Generation of switched memory B cells in response to vaccination in Down syndrome children and their siblings. Vaccine. 2015; 33 (48): 6689–6696. https://doi.org/10.1016/j.vaccine.2015.10.083.

20. Streng B.M.M., Hensen L.C.M., Delemarre E.M., et al. Antibody concentration and function following SARS-CoV-2 vaccination decrease with age in adults and children with Down syndrome. Vaccine. 2026; 73: 128079. https://doi.org/10.1016/j.vaccine.2025.128079.

21. Abbott R.K., Crotty S. Factors in B cell competition and immunodominance. Immunol Rev. 2020; 296 (1): 120–131. https://doi.org/10.1111/imr.12861.

22. Huggard D., Doherty D.G., Molloy E.J. Immune Dysregulation in Children with Down Syndrome. Front Pediatr. 2020; 8: 73. https://doi.org/10.3389/fped.2020.00073.

23. Bartholomeus E., De Neuter N., Meysman P., et al. Transcriptome profiling in blood before and after hepatitis B vaccination shows significant differences in gene expression between responders and non-responders. Vaccine. 2018; 36 (42): 6282–6289. https://doi.org/10.1016/j.vaccine.2018.09.001

24. Páez Chávez J., Gökçe A., Götz T., Gürbüz B. An SIRS-model considering waning efficacy and periodic re-vaccination. Chaos Solitons Fractals. 2025; 196. https://doi.org/10.1016/j.chaos.2025.116439.

25. Patel C., Wang X., Giles M., et al. The role of serological testing for vaccination with a focus on immunocompromised patients: a synthesis of current evidence. Vaccine. 2025; 63: 127659. https://doi.org/10.1016/j.vaccine.2025.127659.

26. Prevention of Viral Hepatitis B: Sanitary and Epidemiological Rules. Moscow: Federal Center for Hygiene and Epidemiology of Rospotrebnadzor; 2008. (In Russ.)

27.