Twinrix Adult Mechanism of Action

Pharmacotherapeutic group: Hepatitis vaccines. ATC code: J07BC20.
Pharmacology: Pharmacodynamics: Twinrix Adult is a combined vaccine formulated by pooling bulk preparations of the purified, inactivated hepatitis A (HA) virus and purified hepatitis B surface antigen (HBsAg), separately adsorbed onto aluminium hydroxide and aluminium phosphate. The HA virus is propagated in MRC₅ human diploid cells. HBsAg is produced by culture, in a selective medium, of genetically engineered yeast cells.
Twinrix Adult confers immunity against HAV and HBV infection by inducing specific anti-HAV and anti-HBs antibodies.
Protection against hepatitis A and hepatitis B develops within 2-4 weeks. In the clinical studies, specific humoral antibodies against hepatitis A were observed in approximately 94% of the adults one month after the first dose and in 100% one month after the third dose (i.e. month 7). Specific humoral antibodies against hepatitis B were observed in 70% of the adults after the first dose and approximately 99% after the third dose.
The 0, 7 and 21 day primary schedule plus a fourth dose at month 12 is for use in exceptional circumstances in adults. In a clinical trial where Twinrix Adult was administered according to this schedule, 82% and 85% of vaccinees had seroprotective levels of anti-HBV antibodies at 1 and 5 weeks respectively following the third dose (i.e. at months 1 and 2 after the initial dose).
The seroprotection rate against hepatitis B increased to 95.1% by three months after the first dose.
Seropositivity rates for anti-HAV antibodies were 100%, 99.5% and 100% at months 1, 2 and 3 after the initial dose. One month after the fourth dose, all vaccinees demonstrated seroprotective levels of anti-HBs antibodies and were seropositive for anti-HAV antibodies.
In a clinical study conducted in subjects over 40 years of age, the seropositivity rate for anti-HAV antibodies and seroprotection rate against hepatitis B of Twinrix Adult following a 0, 1, 6 months schedule were compared with the seropositivity and seroprotection rates of monovalent hepatitis A and B vaccines when administered in opposite arms.
The seroprotection rate against hepatitis B after the administration of Twinrix Adult was 92% and 56% at 7 and 48 months respectively, versus 80% and 43% after the GlaxoSmithKline Biologicals monovalent 20 μg hepatitis B vaccine, and 71% and 31% after another licensed monovalent 10 μg hepatitis B vaccine. Anti-HBs antibody concentrations decreased as age and body mass index increased; they were also lower in male than in female subjects.
The seropositivity rate for anti-HAV antibodies after Twinrix Adult was 97% at both 7 and 48 months versus 99% and 93% after the GlaxoSmithKline Biologicals monovalent hepatitis A vaccine and 99% and 97% after another licensed monovalent hepatitis A vaccine.
Subjects received an additional dose of the same vaccine(s) 48 months after the first dose of the primary vaccination course. One month after this dose, 95% of the subjects vaccinated with Twinrix Adult achieved seroprotective levels of anti-HBV antibodies (≥10 mIU/ml).
In two long-term clinical studies conducted in adults aged 17 years to 43 years, respectively 18 and 25 subjects had evaluable tests 20 years after the primary vaccination with Twinrix Adult; the anti-HAV seropositivity rates were 100% and 96% respectively and the anti-HBs seroprotection rates were 94% and 92%, respectively.
Pharmacokinetics: Evaluation of pharmacokinetic properties is not required for vaccines.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on general safety studies.