Surface protein mutations in chronic hepatitis B patients who received hepatitis B vaccine therapy

Document Type: Original Article


1 Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

2 Digestive Disease Research Center, Shariati Hospital, Tehran, Iran

3 Department of Epidemiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

4 Keyvan Virology Laboratory, Tehran, Iran

5 Imam Khomeini Hospital, Tehran, Iran

6 Baqiyatallah Research Center for Gastroenterology and Liver Disease, Tehran, Iran

7 Robert-Koch-Haus Virchowstr.179.45147, Essen, Germany


Objective (s):The aim of this study was to determine the correlation between vaccine therapy and appearance of mutations in hepatitis B surface antigen (HBsAg)-positive chronic hepatitis B virus (HBV) patients.
Materials and Methods: 16 patients received the HBV vaccine and another 16 individuals from the control group did not. The surface gene was amplified and directly sequenced from samples prior to vaccination and six months after the third dose.
Results:Only one patient lost HBsAg. 48 and 44 amino acid mutations were found before and after vaccine therapy in the vaccine group respectively, 51 of which (55.4%) occurred in immune epitopes: 5 were in B cell, 21 in T helper (Th), and 25 in cytotoxic T-lymphocyte (CTL) epitopes. In the control group, 35 and 41 amino acid substitutions were found before and after therapy, respectively. 32 (42%) of 76 amino acid changes occurred within immune epitopes. There were no differences in age, gender, and duration of chronicity in both patient and control groups in terms of the frequency and the patterns of mutations.
Conclusion: In chronic carriers who already had HBsAg variants selected by the host-immune response, any immune stimulation by the vaccine had no effect on the chronic state of these patients or selected any remarkable escape mutants. Newer strategies should be considered based on third generation or the use of DNA vaccines or new adjuvants.


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