THE LONG-TERM IMMUNOGENICITY OF RECOMBINANT HEPATITIS B VIRUS (HBV) VACCINE: CONTRIBUTION OF UNIVERSAL HBV VACCINATION IN ITALY

Sunday, 29th of March 2015

"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."

THE LONG-TERM IMMUNOGENICITY OF RECOMBINANT HEPATITIS B VIRUS (HBV) VACCINE: CONTRIBUTION OF UNIVERSAL HBV VACCINATION IN ITALY

Nicola Coppola¹^*†, Anna Rita Corvino², Stefania De Pascalis¹, Giuseppe Signoriello³, Eliana Di Fiore², Albert Nienhaus⁴, Evangelista Sagnelli¹ and Monica Lamberti²^†

* Corresponding author: Nicola Coppola nicola.coppola@unina2.it
† Equal contributors

Author Affiliations

¹ Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Via L. Armanni 5, Naples 80133, Italy

² Department of Experimental Medicine, Section of Hygiene, Occupational Medicine and Forensic Medicine, Second University of Naples, Naples, Italy

³ Department of Mental Health and Public Medicine, Section of Statistic, Second University of Naples, Naples, Italy

⁴ 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

For all author emails, please log on.

BMC Infectious Diseases 2015, 15:149 doi:10.1186/s12879-015-0874-3

Nicola Coppola and Monica Lamberti contributed equally to this work.

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2334/15/149

Received:	21 October 2014
Accepted:	10 March 2015
Published:	25 March 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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 <10 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.

Keywords:

HBV infection; HBV vaccination; Anti-HBs titer; Healthcare students

Background

Infection with hepatitis B virus (HBV) is a leading cause of acute and chronic liver disease worldwide [1]. The World Health Organization (WHO) estimates that, globally, about 2 billion people have been infected with HBV, more than 350 million are chronically infected, and nearly one million per year die from its acute or chronic sequelae, such as fulminant hepatitis, liver cirrhosis, and hepatocellular carcinoma [2]. The prevalence of HBV-related hepatitis varies across countries: in industrialized West European countries and North America, the prevalence of HBV surface antigen (HBsAg) positivity in the general population is less than 2% (low endemicity); in most countries of the Mediterranean, East Europe, and Asia it ranges between 2–8% (intermediate endemicity); whereas it is over 8% in some developing countries in Far-East Asia and Sub-Saharan Africa (high endemicity) [3],[4].

In Italy, the epidemiology of HBV infection has changed substantially over the last 50 years: there has been a remarkable, progressive reduction in the incidence of acute hepatitis B (from 10/100,000 inhabitants in 1984 to 0.85/100,000 in 2012) and in the percentage of HBV-related cases among patients with chronic hepatitis (from 60% in 1975 to nearly 8% in 2010) [5],[6]; moreover, the prevalence of chronic carriers of HBsAg in the general population has decreased from nearly 3% in the 1980s to 1% or less in 2010 [5]. The reasons for this may be due to a number of relevant events occurring in Italy over the last three decades, including improved socio-economic conditions; a consistent reduction in the number of large families, in which HBV is often transmitted among siblings [7]; the national educational campaigns against HIV infection; mandatory screening for women during pregnancy and/or at the time of delivery; and a mass vaccination campaign against HBV [8],[9].

Universal HBV vaccination of newborn babies was introduced in Italy in 1991 and was extended to 12-year-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 schedule involves HBV vaccination doses at months 0, 1, and 6, starting from the third month of life for infants. In Italy, HBV vaccination is also recommended for people at risk of acquiring HBV infection [10]-[12].

A debated issue is how long a protective antibody response may persist after vaccination. A study performed in Italy in 2003 showed that after primary vaccination of infants and adolescents, the antibody response persisted at levels considered protective (>10 IU/L) for at least 10 years in most subjects [13]. However, data on the persistence of the efficacy of vaccination for longer periods are scant and fragmentary [14]-[18].

The present study was therefore carried out to evaluate the long-term immunogenicity and effectiveness of HBV vaccination and to identify independent predictive factors of long-term immunogenicity. To this end, students attending the medical and healthcare schools of the Second University of Naples, Italy, were enrolled in this study.