VALUTAZIONE DELL'EFFICACIA E DELL'IMMUNOGENICITÀ A LUNGO TERMINE DELLA VACCINAZIONE ANTI-EPATITE B IN ITALIA: ATTUALITÀ E PROSPETTIVE FUTURE.
Tesi di Dottorato
Data di Pubblicazione:
2017
Citazione:
VALUTAZIONE DELL'EFFICACIA E DELL'IMMUNOGENICITÀ A LUNGO TERMINE DELLA VACCINAZIONE ANTI-EPATITE B IN ITALIA: ATTUALITÀ E PROSPETTIVE FUTURE / C. Galli ; tutor: L. Romanò ; coordinatore del Dottorato: C. La Vecchia. DIPARTIMENTO DI SCIENZE BIOMEDICHE PER LA SALUTE, 2017 Mar 29. 29. ciclo, Anno Accademico 2016. [10.13130/c-galli_phd2017-03-29].
Abstract:
INTRODUCTION
Hepatitis B virus (HBV) is a partially double stranded DNA virus of the Hepadnaviridae family which includes related viruses responsible for liver injuries in animals. On the basis of genetic variability, human HBV strains are currently divided into 8 major (A-H) and 2 minor (I-J) genotypes with a different geographical distribution.
HBV is mainly carried in blood but also in other body fluids such as saliva, semen and vaginal secretions. It is usually transmitted by vertical route in developing and highly endemic countries and by horizontal route, especially by unsafe sexual contacts and intravenous drug use, in developed countries with low or intermediate endemicity.
Nowadays, hepatitis B is a potentially life-threatening liver infection because safe and effective vaccines are available since ‘80s. However, such infection is still a serious public health problem worldwide. It is a leading cause of acute and chronic liver disease. Currently about 240 million people are estimated to be chronically infected with HBV and more than 686,000 individuals die each year due to HBV-related liver complications, including cirrhosis and liver cancer. Vaccination is the most effective and economically favourable measure to control and prevent hepatitis B on global scale.
The viral genome (HBV-DNA) consists of 4 partially overlapping Open Reading Frames (ORFs): in particular ORF pre-C/C encodes for the core protein (HBc) and ORF pre-S/S encodes for the enveloped proteins, among which the most represented is the viral surface antigen (HBsAg). Specific antibodies against hepatitis B core protein (anti-HBc) generally indicate a natural exposure to HBV. Instead, HBsAg is the main component of the currently hepatitis B vaccines since it contains the viral antigenic determinant common to all HBV strains, called a determinant, which induces the host immune system to produce specific neutralizing anti-HBs antibodies able to recognized the viral protein HBsAg in its originally conformation, thus conferring protection. HBV strains with mutations within the a determinant can cause breakthrough infections also in immunized subjects.
In Italy, hepatitis B vaccination started in 1983 targeted to individuals at increased risk of infection and then became mandatory in 1991 for all infants and, until the end of 2003, also for 12-year-olds. The first hepatitis B vaccines were plasma-derived, soon replaced by monovalent vaccines manufactured by recombinant DNA technology. These vaccines were proven to be highly immunogenic and able to confer seroprotection (anti-HBs concentration ≥10 IU/l after primary immunisation with a 3-dose vaccination series) in over 90-95% of healthy children and adults. However their long-term protection is still a debated issue.
Moreover, from the XXIX century combined vaccines started to be used for infant immunisation. In 2000, two hexavalent vaccines (Hexavac, Sanofi Pasteur MSD and Infanrix Hexa, GlaxoSmithKline) were licensed in Europe for primary immunisation of children against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and Haemophilus influenzae B. In 2005, the marketing authorization of Hexavac vaccine was suspended by the European Medicines Agency (EMA) because of concerns about the long-term immunogenicity of its hepatitis B component. A surveillance programme has been undertaken to verify the long-term protection against HBV conferred by such hexavalent vaccine.
Up till now, the Italian hepatitis B vaccination strategy was a success: in fact it has drastically reduced the incidence of acute infections and the rate of serological HBV markers. However, this policy needs to be constantly monitored to verify its impact in keeping the infection under control. This PhD thesis resumes t
Tipologia IRIS:
Tesi di dottorato
Elenco autori:
C. Galli
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