Hepatitis A antibody titres after infection and immunization: implications for passive and active immunization

Titres of antibodies against hepatitis A virus (HAV) were determined in patients, in donors, and in volunteers after active, passive, and combined immunization. Highest titres were found in recently infected persons: in 109 IgM anti-HAV positive persons, the geometric mean titre (GMT) was 15,400 mIU/ml. The GMT in 265 anti-HAV positive blood donors was 10,700 mIU/ml. The anti-HAV seroprevalence in 19,746 donors increases with age: at the age of 40 years, 50% have antibodies. Titres after active, passive, and combined immunization were studied in three groups: 51 persons received inactivated HAV vaccine at months 0, 1, and 6. The GMT after the booster was 3,400 mIU/ml at month 7. All persons produced more than 100 mIU/ml anti-HAV. Forty-nine persons received both 5 ml immunoglobulin and three vaccinations, yielding a GMT of 1,300 mIU/ml at month 7. One person in this group produced less than 100 mIU/ml anti-HAV. Forty-nine persons received 5 ml immunoglobulin intramuscularly. At day 5 the GMT was 96 mIU/ml. The estimated minimum protective level (10 mIU/ml) was reached in 3 months. Hepatitis A vaccination may supersede the use of immunoglobulin as prophylaxis for travellers to endemic areas. Passive immunization remains necessary for protection during outbreaks. The dosage regimen for passive immunization is based on old studies using preparations with unknown anti-HAV content. Concern regarding the antibody levels in immunoglobulin preparations is justified; the prevalence of HAV antibodies in developed countries continues to fall. Our results indicate that dosage regimens should be reconsidered. Dosage should be deduced logically from the anti-HAV antibody content of the immunoglobulin preparation.