Hepatol Int. 2018 Aug 7. doi: 10.1007/s12072-018-9890-x. [Epub ahead of print]
Multiple doses of hepatitis B recombinant vaccine for chronic hepatitis B patients with low surface antigen levels: a pilot study.
Lai MW1,2,3, Hsu CW2,3, Lin CL2,4, Chien RN2,4, Lin WR2,3, Chang CS2, Liang KH2,5, Yeh CT6,7.
Author information
1
Division of Pediatric Gastroenterology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan.
2
Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan.
3
Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
4
Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
5
Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan.
6
Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan. [email protected].
7
Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan City, Taiwan. [email protected].
Abstract
BACKGROUND:
Seroclearance of hepatitis B surface antigen (HBsAg) has been rarely achieved in the treatment of chronic hepatitis B (CHB) patients. We administered HBsAg-based recombinant vaccine in patients with low HBsAg concentrations.
METHODS:
Twenty hepatitis B e antigen-negative patients, with HBsAg < 1000 IU/ml, were enrolled. Vaccines were administered every 8 weeks for 48 weeks (seven doses). HBsAg levels and anti-HBs were assayed longitudinally until 48 weeks post-vaccination. HLA genotyping and cDNA microarray were performed to search for response predictors.
RESULTS:
Nineteen patients completed the study. At the end of vaccination, HBsAg declined significantly (Δ = - 0.27 ± 0.49 log IU/ml, p = 0.0005). The annual decline rate was significantly greater than that of an age-, gender-, and baseline HBsAg-matched control group (Δ = - 0.18 ± 0.46 versus + 0.11 ± 0.42 log IU/ml/year; p = 0.0229). Two patients achieved HBsAg seroclearance. Fourteen had significant HBsAg decline (Δ = - 0.64 ± 0.88 log IU/ml). No significant adverse events occurred during the trial. cDNA microarray identified the top up- and down-regulated genes in responders as HLA-DQ and HLA-DMB, respectively. HLA genotyping identified HLA-DQB1*04, HLA-DRB1*04, and HLA-B*40 as predictors for non-response (p = 0.0499, 0.0152, and 0.0314, respectively).
CONCLUSIONS:
In low-level HBsAg CHB patients, serial HBsAg-based vaccinations were safe, resulting in significant HBsAg decline. HLA gene expression and genotypes played a role in vaccine responsiveness (ClinicalTrials.gov Identifier: NCT01817725).
KEYWORDS:
Hepatitis B virus; Human leukocyte antigen; Surface antigen clearance; Therapeutic vaccine; Vaccine
不明白你的意思.
病毒变异可能影响疫苗反应.
"Hepatitis B virus envelope protein contains major
immunogenic epitopes. As a result, mutations in the major
hydrophilic region (MRH, aa 99–169) or ‘‘a’’ determinant
(aa 124–147) are expected to impact the vaccine response."
乙型肝炎病毒包膜蛋白含有主要成分
免疫原性表位。 结果，主要突变
亲水区（MRH，aa 99-169）或'a''决定因素
（aa 124-147）预计将影响疫苗反应.作者: ddy123 时间: 2018-8-10 10:28