title: Repeated vaccinations do not improve specific immune defenses against Hepatitis B in non-responder health care workers.
abstract: Hepatitis B is a major infectious occupational hazard for health care workers and can be prevented with a safe and effective vaccine. The serum titer of anti-HBsAg antibodies is the most commonly used correlate of protection and post-vaccination anti-HBsAg concentrations of ≥ 10 mIU/ml are considered protective. Subjects with post-vaccination anti-HBsAg titers of <10 mIU/ml 1-6 months post-vaccination, who tested negative for HBsAg and anti-HBc, are defined as non-responders. The question of whether non-responders should be repeatedly vaccinated is still open. The aim of the study was to (i) evaluate the distribution of lymphocyte subpopulations and the percentage of HBsAg-specific memory B cells in responders and non-responders (ii) assess whether non-responders can be induced to produce antibodies after administration of a booster dose of vaccine (iii) determine whether booster vaccination increases the number of specific memory B cells in non-responders. Combining flow-cytometry, ELISPOT and serology we tested the integrity and function of the immune system in 24 health care workers, confirmed to be non-responders after at least three vaccine injections. We compared the results with those obtained in 21 responders working in the same institution. We found that the great majority of the non-responders had a functional immune system and a preserved ability to respond to other conventional antigens. Our most important findings are that the frequency of HBsAg-specific memory B cells is comparable in non-responders and controls and that booster immunization does not lead either to antibody production or memory B cell increase in non-responders.
authors.affiliation: Health Technology Assessment & Safety Research Unit and Occupational Medicine Service, Department of Laboratories, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Zaffina
authors.affiliation: Immunology Unit, Immunology and Pharmacotherapy Research Area, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marcellini
authors.affiliation: Health Technology Assessment & Safety Research Unit and Occupational Medicine Service, Department of Laboratories, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy.
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Santoro
authors.affiliation: Immunology Unit, Immunology and Pharmacotherapy Research Area, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Scarsella
authors.affiliation: Health Technology Assessment & Safety Research Unit and Occupational Medicine Service, Department of Laboratories, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Camisa
authors.affiliation: Health Technology Assessment & Safety Research Unit and Occupational Medicine Service, Department of Laboratories, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Vinci
authors.affiliation: Paediatric Emergency Department, Department of Laboratories, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Musolino
authors.affiliation: Department of Pediatrics, Department of Laboratories, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Nicolosi
authors.affiliation: Immunology Unit, Immunology and Pharmacotherapy Research Area, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy. Electronic address: manuelaanjosm.rosado@gmail.com.
authors.forename: M Manuela
authors.initials: MM
authors.lastname: Rosado
authors.affiliation: Immunology Unit, Immunology and Pharmacotherapy Research Area, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy; Diagnostic Immunology Unit, Department of Laboratories, Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy. Electronic address: rita.carsetti@opbg.net.
authors.forename: Rita
authors.initials: R
authors.lastname: Carsetti
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D006282:Health Personnel; D006509:Hepatitis B / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D012698:Serologic Tests; D055815:Young Adult
chemical_list: D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines
keywords: Anti-HBsAg specific antibodies; Hepatitis B vaccine; Memory B cells; Non-responders