title: The long-term immunogenicity of recombinant hepatitis B virus (HBV) vaccine: contribution of universal HBV vaccination in Italy.
abstract: BACKGROUND
  Universal hepatitis B virus (HBV) vaccination of newborn babies was introduced in Italy in 1991 and was extended to 12-years-old children for the first 12 years of application so as to cover in a dozen years the Italian population aged 0-24 years. The aim of this study was to identify factors associated with long-term immunogenicity against HBV 17 years after primary vaccination in students attending medical schools in Naples, Italy.
  
  
  METHODS
  1,704 students attending the school of medicine, schools of the healthcare professions, or postgraduate medical schools of the Second University of Naples, Italy, from September 2012 to December 2013 were enrolled in this study. Of these, 588 had been vaccinated against HBV in infancy and 1,116 when 12 years old. Multivariate logistic regression analysis was used to identify factors associated with the level of long-term immunogenicity.
  
  
  RESULTS
  All vaccinated subjects were HBsAg/anti-HBc negative: 270 (15.8%) had an anti-HBs titer between 1 and 9 IU/L, 987 (57.9%) between 10 and 400 IU/L, and 447 (26.3%) over 400 IU/L. When compared with the latter two subgroups, those with anti-HBs titers lower than 10 IU/L were younger (24±5.2 years vs. 26±4.9 years, p<0.000), more frequently students attending a healthcare school (59% vs. 47%, p<0.001), and more frequently had been vaccinated in infancy (50% vs. 31.5%, p<0.0001). Multivariate logistic regression identified age at vaccination as the only factor independently associated with an anti-HBs titer<0 IU/L (OR: 2.43; C.I. 95%: 1.57-3.76, p=0.001).
  
  
  CONCLUSIONS
  Universal HBV vaccination in Italy has been more effective in generating a prolonged protective response in subjects vaccinated at adolescence than in infancy. Students with a low anti-HBs titer should be considered for a booster dose because most will be exposed to the risk of acquiring HBV for decades.
authors.affiliation: Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Via L. Armanni 5, Naples, 80133, Italy. nicola.coppola@unina2.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Coppola
authors.affiliation: Department of Experimental Medicine, Section of Hygiene, Occupational Medicine and Forensic Medicine, Second University of Naples, Naples, Italy. annarita.corvino@hotmail.it.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Corvino
authors.affiliation: Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Via L. Armanni 5, Naples, 80133, Italy. stefaniadepascalis77@tiscali.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: De Pascalis
authors.affiliation: Department of Mental Health and Public Medicine, Section of Statistic, Second University of Naples, Naples, Italy. giuseppe.signoriello@unina2.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Signoriello
authors.affiliation: Department of Experimental Medicine, Section of Hygiene, Occupational Medicine and Forensic Medicine, Second University of Naples, Naples, Italy. eliana.difiore@libero.it.
authors.forename: Eliana
authors.initials: E
authors.lastname: Di Fiore
authors.affiliation: Institute for Health Service Research in Dermatology and Nursing (IVDP), Center of Excellence for Epidemiology and Health Service Research for Healthcare Professionals (CVcare), University Medical Center Hamburg-Eppendorf, Hamburg, Germany. a.nienhaus@uke.de.
authors.forename: Albert
authors.initials: A
authors.lastname: Nienhaus
authors.affiliation: Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Via L. Armanni 5, Naples, 80133, Italy. evangelista.sagnelli@unina2.it.
authors.forename: Evangelista
authors.initials: E
authors.lastname: Sagnelli
authors.affiliation: Department of Experimental Medicine, Section of Hygiene, Occupational Medicine and Forensic Medicine, Second University of Naples, Naples, Italy. monica.lamberti@unina2.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Lamberti
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000097:blood*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D007558:Italy; D016015:Logistic Models; D008297:Male; D012189:Retrospective Studies; D014614:Vaccines, Synthetic
chemical_list: D015415:Biomarkers; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D014614:Vaccines, Synthetic