Live attenuated hepatitis A vaccine
Live attenuated hepatitis A virus vaccines (H2 and L-A-1 strains) have been developed, manufactured and licensed in China. Since 2007, hepatitis A vaccines (both inactivated and live) have been integrated into the national immunization programme. Managers of regional immunization programmes may opt to use any of the vaccines. More than 10 million doses of H2 and L-A-1 vaccine are used annually in China. The only other country where the live vaccine is registered is India, where the H2-strain vaccine was licensed in 2005 and is used only on the private market.
An overview of the development and manufacture of hepatitis A vaccines in China was presented to the Committee. The live attenuated H2-strain and L-A-1-strain vaccines were developed from strains isolated from 2 children with hepatitis; they were attenuated with multiple (>25) cell-culture passages. Vaccine lots are made in locally developed human diploid embryonic lung fibroblast cells (termed 2BS). A special additive (comprising trehalose, sodium glutamate, arginine and dextran) is used to stabilize virus titre on lyophilization.
A representative from the Chinese Centre for Disease Control and Prevention presented a brief account of the epidemiology of hepatitis A in China. There is a temporal relationship between the widespread use of hepatitis A vaccines and a decrease in disease incidence. The overall experience of hepatitis A control in China is good, although the parts played by vaccines and socioeconomic or other factors has not been assessed.
Limited data about reactions to H2-strain vaccine during clinical trials and through passive surveillance for both vaccines did not identify any significant safety issues. However, it will be essential to conduct rigorous high-quality postmarketing surveillance in selected communities to measure and monitor safety and adverse reactions. Studies of children vaccinated with live vaccines have shown shedding of the vaccine virus and secondary infection among contacts, so postmarketing surveillance may provide a context in which to conduct specific studies to examine the outcome of secondary infection and virus circulation if it occurs.
In view of the volume of use of live hepatitis A vaccines in China and their potential usefulness outside China, carefully collected and validated data on safety and efficacy will be valuable. Data of particular interest will be molecular markers of attenuation, the genetic stability of attenuation markers after human passage, the safety of orally ingested vaccine virus, and clinical safety and efficacy as demonstrated in well-conducted and sufficiently large clinical trials. The role of the National Regulatory Authority will be of critical importance in providing oversight on the safety of vaccines used in China.