Safety and Immunogenicity of a High-Potency Inactivated Hepatitis A Vaccine.

Background: In recent years, several hepatitis A vaccines have been developed. We wished to evaluate the safety, reactogenicity, and immunogenicity of an inactivated hepatitis A vaccine, containing 1440 EI.U., and to monitor the kinetics of the antibodies monthly for the first year after administration of a single dose of vaccine. Methods: We conducted an open clinical trial, started in March 1992 and completed in July 1993, at two general hospitals and one pediatric hospital in Antwerp, Belgium, with 194 healthy adult healthcare volunteers. Each volunteer received a single dose hepatitis A vaccine, given intramuscularly at month 0 and a booster at month 12. We undertook serologic follow-up of antihepatitis A virus (antiHAV) antibodies and liver enzymes at day 15 and at months 1, 6, 9, 12, and 13. For a random subgroup of participants, blood samples were taken monthly. In addition, all participants noted local and general symptoms following administration of the vaccine. Results: This single dose vaccine was well-tolerated; 2 weeks after the vaccination, 80% of the participants had seroconverted (antiHAV antibodies >=20 mIU/mL); after 1 month, seroconversion reached 99% (geometric mean titer (GMT): 383 mIU/mL). One year after the single dose of vaccine, 94% still had antiHAV antibodies above 20 mIU/mL (GMT: 176 mIU/mL). One month after the booster dose, seroconversion was 100%, and GMT increased from 176 mIU/mL at month 12 to 4775 mIU/mL at month 13. Conclusions: The single dose hepatitis A vaccine is safe and highly immunogenic; it gives a rapid antibody production and a rapid increase of GMT. The persistence of protective antibodies until month 12 allows a booster at month 12. This schedule will easily fit into existing travel or occupational health vaccination schedules and will improve vaccination compliance.

Horizontal transmission of hepatitis B virus.

In 1991-92, a cross-sectional survey in Flanders (Belgium) for hepatitis B virus (HBV) markers among 277 relatives of institutionalised mentally handicapped persons to evaluate the prevalence of hepatitis B and the risk of infection showed that relatives of an HBV positive resident were 7.6 times more likely to be infected than relatives of an HBV seronegative mentally handicapped person. HBV infection among the family members could be attributed in 83% to exposure to an HBV positive resident. This study demonstrated the importance of horizontal transmission among relatives of institutionalised mentally handicapped people, even if family contact is reduced to weekend and holiday activities. We recommend that HBV vaccination policy should be expanded to include relatives of institutionalised mentally retarded people.

Inactivated hepatitis A vaccine: reactogenicity, immunogenicity, and long-term antibody persistence.

This trial evaluated the reactogenicity, kinetics of antibody induction, and long-term immunogenicity of a 720 enzyme-linked immunosorbent assay units (EL.U.) antigen dose of an inactivated hepatitis A vaccine (Havrix, SmithKline Beecham Biologicals, Rixensart, Belgium). One hundred six healthy adult volunteers were enrolled to receive vaccine intramuscularly according to a 0, 1, and 6-month schedule. The vaccine was well tolerated. The most frequently reported local symptom was soreness, observed following 37.1% of all doses. Headache was the most frequently reported general symptom observed following 12.9% of documented vaccine doses. The administration of one vaccine dose induced seropositivity (anti-hepatitis A virus [HAV] > or = 20 mIU/ml) in 91% of all vaccinees 1 month later. The second vaccine dose resulted in seropositivity of the remaining vaccinees at month 2. All subjects remained seropositive for HAV antibodies at month 6, at which time the booster vaccine dose was given. At month 7, all vaccinees had anti-HAV titres > 200 mIU/ml. Serological results obtained at months 12, 18, 24, and 36 showed that antibodies against HAV induced by the vaccine booster dose persist for at least 30 months following its administration. All 49 subjects followed up until month 36 had antibody titres > or = 20 mIU/ml. The geometric mean titre (GMT) decreased by 60% from month 7 to month 12; between month 12 and 36, the GMT decreased by approximately 14% per period of 12 months. According to the vaccine-induced antibody kinetics and the magnitude of antibody level decrease over time, the predicted duration of antibody persistence is estimated to be at least 20 years.

Heat stability of a recombinant DNA hepatitis B vaccine.

The heat stability of a recombinant DNA hepatitis B vaccine was studied in healthy adult volunteers. When compared with vaccine stored at 4 degrees C, heating of the vaccine for 1 week at 45 degrees C or for 1 month at 37 degrees C did not alter the reactogenicity or the ability of the vaccine to elicit antibody titres considered to be protective. These results have significance in situations where the cold chain is broken, as can happen in countries where proper storage and transport facilities are not always available.