Clinical trials of an inactivated hepatitis A vaccine have encompassed 104 studies completed by December 1993 in 27 countries. Studies involved 50,677 subjects and administration of > 120,000 vaccine doses. Results show that the vaccine is safe, clinically well-tolerated, and highly immunogenic in all age groups. A seroconversion rate of 100% is achieved 1 month after primary vaccination. Vaccine-induced antibody titers persist after a primary vaccination course for > or = 1 year with a single dose of 1440 ELISA units (EL.U.) in adults and after two doses of 360 EL.U. in children. A booster dose 6-12 months after the first vaccine dose induces very high antibody titers, which according to a mathematical model, are expected to protect against hepatitis A for > 20 years. The vaccine is equally immunogenic when administered simultaneously with other traveler vaccines, therefore enabling flexible and convenient vaccination against hepatitis A.

Clinical trials have shown that AS03-adjuvanted H5N1 and A(H1N1)pdm09 vaccines are highly immunogenic, although with an increased reactogenicity profile relative to non-adjuvanted vaccines in terms of the incidence of common injection site and systemic adverse events (AEs). We evaluated pooled safety data from 22,521 adults who had received an AS03-adjuvanted H5N1 or A(H1N1)pdm09 influenza or control vaccine with the purpose to identify medically-attended AEs (MAEs), including subsets of serious AEs (SAEs), potentially immune-mediated diseases (pIMDs), and AEs of special interest (AESI), and to explore a potential association of these AEs with the administration of an AS03-adjuvanted influenza vaccine. For participants who had received an AS03-adjuvanted vaccine, the relative risks (RRs) for experiencing a MAE or a SAE compared to control group (participants who had received a non-adjuvanted vaccine or saline placebo) were 1.0 (95% confidence interval [CI]: 0.9; 1.1) and 1.1 (95% CI: 0.9; 1.4), respectively. The overall RRs for experiencing an AESI or a pIMD (AS03-adjuvanted vaccine/control) were 1.2 (95% CI: 0.9; 1.6) and 1.7 (95% CI: 0.8; 3.8), respectively. Thirty-8 participants in the AS03-adjuvanted vaccine group had a pIMD reported after vaccine administration, yielding an incidence rate (IR) of 351.9 (95% CI: 249.1; 483.1) per 100,000 person-years. The estimated IRs in the AS03-adjuvanted vaccine group were greater than the literature reported rates for: facial paresis/VIIth nerve paralysis, celiac disease, thrombocytopenia and ulcerative colitis. These results do not support an association between AS03-adjuvanted H5N1 and A(H1N1)pdm09 vaccines and the AEs collected in the trials included in the analysis.