title: Higher numbers of memory B-cells and Th2-cytokine skewing in high responders to hepatitis B vaccination.
abstract: In the present study, differences in hepatitis B surface antigen (HBsAg)-specific memory B-cell responses between low and high responders to hepatitis B vaccine (HepB), based on levels of antibodies against HBsAg (anti-HBs), were determined. In addition, HBsAg specific T-cell responses between high (anti-HBs level >20,000 IU/L) and low (anti-HBs level <1500 IU/L) responders were compared. Numbers of HBsAg-specific B-cells, plasma immunoglobulin G (Ig) levels, and T-cell cytokine concentrations were measured in low and high responders directly before and one month after the second booster vaccination. In advance, an Enzyme-linked Immunosorbent Spot (ELISpot) Assay was optimized for the determination of HBsAg-specific B-cell responses. The number of HBsAg-specific B-cells was significantly higher (p<0.01) in the high responder group compared to the low responder group after a booster vaccination with HepB. In addition, the plasma IgG levels and numbers of HBsAg-specific B-cells were significantly correlated (RS=0.66, p<0.01). The HBsAg-specific Th1 cell response showed the same values in the low and high responder group and did not change by the booster vaccination with HepB. However, a significant correlation (RS=0.6975, p=0.007) between the IL-13 levels and the plasma IgG levels post-booster was found. Subsequently, the IL-13 level in the high-responder group post-booster was significantly higher compared to the low-responder group. Since activation of the B-cell response after vaccination is induced by Th2 cells and IL-13 is produced by these cells, we conclude that the difference in HBsAg-specific Th2 cells is involved in determining the differences in anti-HBs level and memory B-cell numbers between low and high responders.
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, Bilthoven 3720 BA, The Netherlands; Department of Toxicogenomics, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht 6229 ER, The Netherlands. Electronic address: adoedee@gmail.com.
authors.forename: A M C M
authors.initials: AM
authors.lastname: Doedée
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, Bilthoven 3720 BA, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Kannegieter
authors.affiliation: Centre for Infectious Disease Control Netherlands, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720 BA, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Öztürk
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, Bilthoven 3720 BA, The Netherlands; Department of Toxicogenomics, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht 6229 ER, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: van Loveren
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, Bilthoven 3720 BA, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Janssen
authors.affiliation: Centre for Infectious Disease Control Netherlands, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720 BA, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Buisman
mesh_terms: D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D006509:Hepatitis B / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D018793:Interleukin-13 / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: D016207:Cytokines; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D018793:Interleukin-13
keywords: Anti-HBs levels; HBsAg-specific memory B-cells; HBsAg-specific memory T-cells; Hepatitis B vaccination; IL-13; Low and high responders