RESUMO
BACKGROUND: Hepatitis B virus (HBV) fails to produce appropriate immune responses in some healthy individuals; thus, different strategies have been adopted to promote immune responses. The current study aimed at evaluating the efficacy of HBV vaccine coadministered with tetanus-diphtheria (Td) vaccine compared with HBV vaccine in healthy individuals through measuring hepatitis B surface antibody (HBsAb) levels. MATERIALS AND METHODS: This was a randomized controlled clinical trial, which was implemented in Isfahan, Isfahan Province (Iran) in 2013. One hundred and forty healthy individuals, whose HBsAb titers were less than 10 IU/L were recruited. The subjects were randomly assigned to either in intervention or control trials. The control group received 40 µg of recombinant HBV vaccines intramuscularly injected at 0, 1, and 6 months; however, the intervention group was simultaneously vaccinated by Td with the first dose of HBV vaccine. HBV antibody levels (titer) were measured before the vaccination and 6 months after the last vaccination. RESULTS: Antibody titers of the subjects in the intervention and control groups increased from 5.07 ± 2.9 IU/L to 744.45 ± 353.07 IU/L and from 4.45 ± 3.4 IU/L to 589.94 ± 353 IU/L, respectively (both P < 0.001). Also, the mean difference of antibody titer was significantly different between the two groups (P = 0.011). CONCLUSION: Td vaccination can be applied as a feasible approach to promote efficient and persistent immunity in healthy individuals with insufficient HBsAb titers.
RESUMO
Background: This study aimed to explore the molecular mechanism of the coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) serological pattern via intensive characterization of HBV s gene in both chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients. Method: A total of 73 HBsAg+/HBsAb+ patients (CHB = 36, HCC = 37) and 96 HBsAg+/HBsAb- patients (CHB = 47, HCC = 49) were enrolled from 13 medical centers in China. The sequence features were elaborated based on the combination of next-generation sequencing (NGS) and multidimensional bioinformatics analysis. Results: The 16 high-frequency missense mutations, changes of stop codon mutation, clustering, and random forest models based on quasispecies features demonstrated the significant discrepancy power between HBsAg+/HBsAb+ and HBsAg+/HBsAb- in CHB and HCC, respectively. The immunogenicity for cytotoxic T lymphocyte (CTL) epitope Se and antigenicity for the major hydrophilic region (MHR) were both reduced in HBsAg+/HBsAb+ patients (CTL Se: p < 0.0001; MHR: p = 0.0216). Different mutation patterns were observed between HBsAg+/HBsAb+ patients with CHB and with HCC. Especially, mutations in antigenic epitopes, such as I126S in CHB and I126T in HCC, could impact the conformational structure and alter the antigenicity/immunogenicity of HBsAg. Conclusion: Based on NGS and bioinformatics analysis, this study indicates for the first time that point mutations and quasispecies diversities of HBV s gene could alter the MHR antigenicity and CTL Se immunogenicity and could contribute to the concurrent HBsAg+/HBsAb+ with different features in HCC and CHB. Our findings might renew the understanding of this special serological profile and benefit the clinical management in HBV-related diseases.