Bahar ÇUHACI ÇAKIR, Aslınur ÖZKAYA PARLAKAY, Aysun KARA UZUN, Zeynep PAKSOY

Booster Dose Vaccine Response among Children Who were Primary Hepatitis B Vaccine Non-Responders and Sensitive Groups Concerning Vaccine Response

Amaç: Çalışmada birincil hepatit B aşı yanıtsız 2-16 yaş aralığındaki 83 çocukta, 0, 1 ve 6. ay aşı şeması uygulanarak elde edilen hatırlatma doz aşı yanıtları değerlendirilmiş ve aşı yanıtında hassas gruplar belirlenmeye çalışılmıştır. Gereç ve Yöntemler: Küçük cerrahi girişimler öncesi yapılan tetkikler sonrasında birincil hepatit B aşı yanıtsızlığı saptanan 2-16 yaş aralığındaki sağlıklı 83 çocuğa, 2. kez 0, 1 ve 6. aylarda 3 doz 10 μg HBsAg içeren Euvax B aşısı deltoid kasa 0.5ml kas içine uygulanmıştır. Çocuklardan birinci aşıdan 1, 6 ve 7. ay sonra olmak üzere, 3 kez kan alınarak antiHBs titresi enzyme-linked immunosorbent assay tekniği ile değerlendirilmiştir. Bulgular: Çocukların yaş ortalaması 9.3±3.6 yıl (2-15.9) bulunmuştur. Birinci aşı sonrası anti-HBs ortalama geometrik konsantrasyonu 537.97±377.51 mIU/mL (0.6-1000), 2. aşı sonrası 309.33± 337.45 mIU/mL (8-1000), 3. aşı sonrası 609.78±347.43 mIU/mL (11.1-1000) bulunmuştur. Birinci aşı sonrası tetkik yapılabilen 81 çocuk arasında T1’de antiHBs-positive serokonversiyon oranı, aşı öncesi anti-HBs titresi 1 mIU/mL’nin altında olan çocuklarda diğer gruba göre istatistiksel anlamlı biçimde daha düşük bulunmuştur (p=0.01, Z -3.29, U 469). Bu 2 grup arasında T6 ve T7’de istatistiksel fark saptanmamıştır. Malnütrisyonlu hastalarda T6 ve T7’de anti-HBs positive serokonversiyon oranı diğer gruba göre istatistiksel anlamlı olarak daha yüksek bulunmuştur (p=0.008, Z -2.56, U 60.5, p=0.03, Z -2.11, U 26.5). Sonuç: İki doz aşıya rağmen T6’daki hızlı düşüşe bakıldığında, anti-HBs serokonversiyon oranı ve anti-HBs ortalama geometrik konsantrasyon değerleri hatırlatma doz sayısından ziyade, hatırlatma yapılmasına, aşı öncesi anti-HBs titresine ve anti-HBs titresi bakma zamanıyla ilgili gözükmektedir. Ancak, aşı öncesi anti-HBs titresi

Booster Dose Vaccine Response among Children Who were Primary Hepatitis B Vaccine Non-Responders and Sensitive Groups Concerning Vaccine Response

Objective: In this study, booster dose vaccine response was evaluated after performing a vaccine schedule at 0,1st and 6th months among 83 children aged between 2 and 16 years who were primary hepatitis B vaccine nonresponders and we tried to determine which groups were sensitive concerning vaccine response.Material and Methods: Euvax B vaccine which included 10 μg HBsAg was administered in 3 doses for the secondtime at 0, 1 and 6 months as 0.5 ml intramuscularly in the deltoid muscle to 83 healthy children aged between 2 and 16years who were primary hepatitis B vaccine non-responders and their vaccine status was determined with tests beforeminor surgery. Blood tests were taken three times from children at 1, 6 and 7 months after the first vaccination and antiHBs titer was evaluated by using enzyme-linked immunosorbent assay technique.Results: The mean age of the children was 9.3±3.6 years (2-15,9 years). The anti-HBs geometric mean concentrationwas found to be 537.97±377.51 mIU/mL (0.6-1000) after the first vaccination, as 309.33± 337.45 mIU/mL (8-1000)after the second vaccination and as 609.78±347.43 mIU/mL (11.1-1000) following the third vaccination. Anti-HBspositive conversion rates in T1 were compared in 81 children who had been checked after the first vaccination and antiHBs positive conversion rates were found to be significantly lower in children whose anti-HBs titer was under 1 mlU/mlbefore vaccination (p=0,01, Z -3.29, U 469). There was no difference concerning T6 and T7 between these two groups.Anti-HBs positive conversion rates in T6 and T7 were found to be significantly higher in children with malnutrition(p=0.008, Z -2.56, U 60.5, p=0.03, Z -2.11, U 26.5).Conclusion: When observing the rapid decrease in T6 in contrast with the two dose vaccination, it is thought that antiHBs seroconversion rates and anti-HBs geometric mean concentration are related with reminding, anti-HBs titer beforevaccination and checking time of anti-HBs rather than the number of reminding doses. In fact, we believe that 3 dosevaccination is better among those children whose anti-HBs titer is under

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1. Immunization Coverage. Availablefrom:http://www.who.int/mediacentre/factsheets/fs378/en/. Accessed date: 1 Haziran, 2016
2. Zhuang GH,Yan H, Wang XL. Risk factors of and mechanism for non-responsiveness to hepatitis B vaccination. Zhonghua Gan Zang Bing Za Zhi 2006;14:157-60.
3. Averhoff F, Mahoney F, Coleman P, Schatz G, Hurwitz E, Margolis H. Immunogenicity of hepatitis B Vaccines. Implications for persons at occupational risk of hepatitis B virus infection. Am J Prev Med 1998;15:1–8.
4. http://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html (8.5.2017)
5. Toy M, Önder FO, Wörmann T, Bozdayi AM, Schalm SW, Borsboom GJ, et al. Age- and region-specific hepatitis B prevalence in Turkey estimated using generalized linear mixed models: A systematic review. BMC Infectious Diseases 2011;11:337.
6. Bonanni P, Pesavento G, Boccalini S, Bechini A. Perspectives of public health: Present and foreseen impact of vaccination on the epidemiology of hepatitis B. J Hepatol 2003;39:224-9.
7. Ozmert EN. Dünya’da ve Türkiye’de aşılama takvimindeki gelişmeler. Çocuk Sağlığı ve Hastalıkları Dergisi 2008;51:168-75.
8. Jafarzadeh A, Zarei S, Shokri F. Low dose revaccination induces robust protective anti-HBs antibody response in the majority of healthy non-responder neonates. Vaccine 2008;26:269-76.
9. Behre U, Bleckmann G, Crasta PD, Leyssen M, Messier M, Jacquet JM. Long-term anti-HBs antibody persistence and immune memory in children and adolescents who received routine childhood hepatitis B vaccination. Hum Vaccin Immunother 2012;8:813-8.
10. Gilca V, De Serres G, Boulianne N, Murphy D, De Wals P, Ouakki M. Antibody persistence and the effect of a booster dose given 5, 10 or 15years after vaccinating preadolescents with a recombinant hepatitis B vaccine. Vaccine 2013;31:448-51.
11. Fitz Simons D, François G, Hall A, McMahon B, Meheus A, Zanetti A. Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants. Vaccine 2005;23:4158-66.
12. West DJ, Calandra GB. Vaccine induced immunologic memory for hepatitis B surface antigen: Implications for policy on booster vaccination. Vaccine 1996;14:1019-27.
13. Lu CY, Chiang BL, Chi WK, Chang MH, Ni YH, Hsu HM, et al. Waning immunity to plasma-derived hepatitis B vaccine and the need for boosters 15 years after neonatal vaccination. Hepatology 2004;40:1415-20.
14. McMahon BJ, Bruden DL, Petersen KM, Bulkow LR, Parkinson AJ, Nainan O, et al. Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow-up. Ann Intern Med 2005;142:333-41.
15. Hadler SC, Francis DP, Maynard JE, Thompson SE, Judson FN, Echenberg DF, et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. N Engl J Med 1986; 315:209-14.
16. Pan HX, Zeng Y, Song XF, Zhang YJ, Xu K, Liang ZL, et al. Immune response to hepatitis B vaccine with high antigen content in nonresponders after standard primary vaccination in Chinese adults. Vaccine 2014;17:3706-12.
17. Schonberger K, Riedel C, Ruckinger S, Mansmann U, Jilg W, Kries RV. Determinants of Long-term protection after hepatitis B vaccination in infancy: A meta-analysis. Pediatr Infect Dis J 2013;32:307-13.
18. Goncalves L, Albarran B, Salmen S, Borges L, Fields H, Montes H, et al. The nonresponse to hepatitis B vaccination is associated with impaired lymphocyte activation. Virology 2004;326:20-8.
19. Tajiri K, Shimizu Y. Problems and future perspectives of hepatitis B virus vaccination. World J Gastroenterol 2015;21:7074–83.
20. Asturias EJ, Mayorga C, Caffaro C, Ramirez P, Ram M, Verstraeten T, et al. Differences in the immune response to hepatitis B and Haemophilus influenzae type b vaccines in Guatemalan infants by ethnic group and nutritional status. Vaccine 2009;2:3650-4.
21. Poorolajal J, Mahmoodi M, Majdzadeh R, Nasseri-Moghaddam S, Haghdoost A, Fotouhi A. Long-term protection provided by hepatitis B vaccine and need for booster dose: A meta-analysis. Vaccine 2010;28:623-31.
22. Hudu SA, Malik YA, Niazlin MT, Harmal NS, Adnan A, Alshrari AS. Antibody and immune memory persistence post infant hepatitis B vaccination. Patient Prefer Adherence 2013;7:981-6.
23. Chen YS, Chu CH, Wang JH, Lin JS, Chang YC. Predictors of booster response to Hepatitis B vaccine at 15 years of age: A crosssectional school-based study. Pediatr Neonatol 2015;15:174-6.
24. Salama II, Sami SM, Salama SI, Foud WA, Abdel Hamid AT, Said ZN. Persistence of protection to hepatitis B vaccine and response to booster dose among children and adolescents in DakahleyaEgypt. Egypt J Immunol 2014;21:13-26.
25. Çekmez F, Canpolat FE, Erdinç K, Çetinkaya M, Akın O, Pamuk U, et al. Response to hepatitis B vaccine differs by birthweight among neonates. Vaccine 2011;29:3096-7
26. Fan W, Chen XF, Shen C, Guo ZR, Dong C. Hepatitis B vaccine response in obesity: A meta-analysis. Vaccine 2016;34:4835-41.
27. Cuille MAR, Seck A, Njouom R, Chartier L, Sow HD, Mamadou KAS, et al. Low immune response to hepatitis B vaccine among children in Dakar, Senegal. PLoS One 2012;7:1-4.
28. Lin CS, Xie SB, Liu J, Zhao ZX, Chong YT, Gao ZL. Effect of revaccination using different schemes among adults with low or undetectable anti-HBs titers afterhepatitis B virus vaccination. Clin Vaccine Immunol 2010;17:1548-51.
29. Velu V, Nandakumar S, Shanmugam S, Jadhav SS, Kulkarni PS, Thyagarajan SP. Comparison of three different recombinant hepatitis B vaccines: GeneVac-B, Engerix B and Shanvac B in high risk infants born to HBsAg positive mothers in India. World J Gastroenterol 2007;13:3084-9.
30. Zhang Y, Jiang W, Fan Y, Wen J, Hao W, Qian M. Engineering enhancement of the immune response to HBV DNA vaccine in mice by the use of LIGHT gene adjuvant. J Virol Methods 2008;153:142-8.
31. Rapicetta M, D’Ugo E, Argentini C, Catone S, Canitano A, Giuseppetti R, et al. New perspectives for hepatitis B vaccines and immunization. Vaccine 2009;27:3271-5.
32. Chen Y, Lv H, Gu H, Cui F, Wang F, Yao J, et al. The effects of different dosage levels of hepatitis B vaccine as booster on antiHBs-negative children 5-15 y after primary immunization; China, 2009-2010. Hum Vaccin Immunother 2014;10:498-504.
33. Qawasmi M, Samuh M, Glebe D, Gerlich WH, Azzeh M. Agedependent decrease of anti-HBs titers and effect of booster doses using 2 different vaccines in Palestinian children vaccinated in early childhood. Hum Vaccin Immunother 2015;11:1717-24.