Immune response to different types of hepatitis B vaccine booster doses 2-32 years after the primary immunization schedule and its influencing factors
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
Authors: Zhao, Yu-Liang; Pan, Lu-Lu; Hao, Zhi-Yong; Jin, Fei; Zhang, Yan-Hong; Li, Min-Jie; Zhang, Xin-Jiang; Han, Bi-Hua; Zhou, Hai-Song; Ma, Tian-Li; Wang, Feng; Ma, Jing-Chen; Shen, Li-Peng; Li, Qi
Abstract
Objective: To assess the immune effect of different types of hepatitis B vaccine (HepB) booster doses 2-32 years after primary immunization, explore the influencing factors, and offer guidance regarding the necessity and timing of boosters. Methods: In total, 1163 participants who were born from 1986 to 2015, received the HepB full-course primary vaccination, were hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) negative, and had hepatitis B surface antibody (anti-HBs) <10 mIU/mL were enrolled. Individuals were randomly divided into two groups and received a booster dose of HepB. Venous blood samples were collected 30 days later and tested for anti-HBs. Results: In total, 595 and 568 individuals received a single dose of HepB (CHO) and HepB (SC), respectively. Venous blood samples were obtained from 1079 vaccinees (CHO: 554, SC: 525). The seroconversion rates were 93.68% (519/554) and 86.67% (455/525) (p < 0.05), with geometric mean concentrations (GMCs) of 426.58 mIU/ml and 223.8 mIU/ml, respectively. This result indicated that BMI, smoking status, vaccine types of booster and prebooster anti-HBs concentration significantly influenced anti-HBs levels. Only BMI, prebooster anti-HBs concentrations and booster types were different between the anti-HBs positive and negative groups. Conclusions: Participants boostered with HepB (CHO) had a relatively higher seroconversion rate than those boostered with HepB (SC). The high seroconversion rates in the two groups suggested that the subjects remained protected despite low circulating antibodies, so there is currently no urgent need for booster immunization. Factors including BMI > 25 and prebooster anti-HBs concentration <2.5 mIU/mL, which contributed to lower responses to a booster dose, might indicate a greater risk of breakthrough infection. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
Effects of Hepatitis B Surface Antigen on Virus-Specific and Global T Cells in Patients With Chronic Hepatitis B Virus infection
GASTROENTEROLOGY
Authors: Le Bert, Nina; Gill, Upkar S.; Hong, Michelle; Kunasegaran, Kamini; Tan, Damien Z. M.; Ahmad, Raidah; Cheng, Yang; Dutertre, Charles-A.; Heinecke, Andreas; Rivino, Laura; Tan, Anthony; Hansi, Navjyot K.; Zhang, Min; Xi, Sujuan; Chong, Yutian; Pflanz, Stefan; Newell, Evan W.; Kennedy, Patrick T. F.; Bertoletti, Antonio
Abstract
BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is characterized by the presence of defective viral envelope proteins (hepatitis B surface antigen [HBsAg]) and the duration of infection- most patients acquire the infection at birth or during the first years of life. We investigated the effects of these factors on patients' lymphocyte and HBV-specific T-cell populations. METHODS: We collected blood samples and clinical data from 243 patients with HBV infection (3-75 years old) in the United Kingdom and China. We measured levels of HBV DNA, HBsAg, hepatitis B e antigen, and alanine aminotransferase; analyzed HBV genotypes; and isolated peripheral blood mononuclear cells (PBMCs). In PBMCs from 48 patients with varying levels of serum HBsAg, we measured 40 markers on nature killer and T cells by mass cytometry. PBMCs from 189 patients with chronic infection and 38 patients with resolved infections were incubated with HBV peptide libraries, and HBV-specific T cells were identified by interferon gamma enzyme-linked immune absorbent spot (ELISpot) assays or flow cytometry. We used multivariate linear regression and performed variable selection using the Akaike information criterion to identify covariates associated with HBV-specific responses of T cells. RESULTS: Although T- and natural killer cell phenotypes and functions did not change with level of serum HBsAg, numbers of HBs-specific T cells correlated with serum levels of HBsAg (r = 0.3367; P < .00001). After we performed the variable selection, the multivariate linear regression model identified patient age as the only factor significantly associated with numbers of HBs-specific T cells (P = .000115). In patients younger than 30 years, HBs-specific T cells constituted 28.26% of the total HBV-specific T cells; this value decreased to 7.14% in patients older than 30 years. CONCLUSIONS: In an analysis of immune cells from patients with chronic HBV infection, we found that the duration of HBsAg exposure, rather than the quantity of HBsAg, was associated with the level of anti-HBV immune response. Although the presence of HBs-specific T cells might not be required for the clearance of HBV infection in all patients, strategies to restore anti-HBV immune responses should be considered in patients younger than 30 years.