[Long-term immunogenicity and effectiveness of live attenuated hepatitis A vaccine (H2-strain)-a study on the result of 15 years' follow up].

OBJECTIVE: To evaluate the long-term immunogenicity and effectiveness of live attenuated hepatitis A (HA) vaccine (H2 strain) after one dose injection, through a 15 years' follow up observation. METHODS: A total of 220 children with negative anti-HAV antibody (aged 1-3 y) were involved and followed up in Jiaojiang district, Taizhou city, Zhejiang province. Indicators would include seroconversion and geometric mean titer (GMT) levels after inoculation the vaccine with single dose at 2 m, 12 m, 6 years, 10 years and 15 years. Epidemiological observation was carried out within the 15 years to evaluate the relationship between vaccine coverage, the incidence of HA and the overall effectiveness. In the studied population, serum was tested by ELISA (calibrated by WHO international reference) and ABBOTT Axsym HAVAB mEIA. RESULTS: Seroconversion rates were found to be 98.6% and 81.3% after 2 months and 15 years of inoculation and slowly decreased. GMT level was 128 mIU/ml after 15 years, significantly higher than the required protective level of 20 mIU/ml, recommended by WHO experts. Effectiveness through the 15-year follow up program showed a significant correlation between vaccine coverage and incidence of HA in 1-15 years aged group (Kendall-Rank test, τ =-0.931, P<0.01). There was no HA case seen among the observed accumulated 236 413 person-year vaccines, compared to 4 HA cases discovered in the 27 206 person-year of the non-vaccinees. The overall protective rate reached 100%. Through a mass vaccination program on children, the whole population established an immune-defence to enable the incidence of HA decreased by 96.7%. CONCLUSION: The long-term immunogenicity and effectiveness of live attenuated hepatitis A vaccine (H2 strain) after one dose injection could last as long as 15 years.

Molecular evolution of hepatitis A virus in a human diploid cell line.

AIM: To investigate the hotspots, direction, and the time course of evolution of hepatitis A virus in the process of consecutive cell culture passage in human KMB17 diploid cells. METHODS: Wild type hepatitis A virus H2w was serially propagated in KMB17 cells until passage 30, and the full-length genomes of H2w and its six chosen progenies were determined by directly sequencing RT-PCR products amplified from viral genomic RNA. Alignment comparison of sequences from H2w with its six progenies and phylogenetic analysis of the whole VP1 region from H2w, progenies of H2w, and other cell culture adapted hepatitis A virus were then carried out to obtain data on the molecular evolution of hepatitis A virus in the process of consecutive passage in KMB17 cells. RESULTS: Most of the mutations occurred by passage 5 and several hotspots related to adaptation of the virus during cell growth were observed. After that stage, few additional mutations occurred through the remaining duration of passage in KMB17 cells except for mutation in the virulence determinants, which occurred in the vicinity of passage 15. The phylogenetic analysis of the whole VP1 region suggested that the progenies of H2w evolved closely to other cell culture adapted hepatitis A virus, i.e. MBB, L-A-1, other than its progenitor H2w. CONCLUSION: Hepatitis A virus served as a useful model for studying molecular evolution of viruses in a given environment. The information obtained in this study may provide assistance in cultivating the next generation of a seed virus for live hepatitis A vaccine production.

Persistent efficacy of live attenuated hepatitis A vaccine (H2-strain) after a mass vaccination program.

BACKGROUND: Live attenuated hepatitis A vaccine (H2 strain) is widely applied in prevention of hepatitis A epidemic in China and other countries now. It is essential to observe and confirm the vaccine immune efficacy, population antibody level and its persistent efficacy after mass immunization. METHODS: A total of 220 children with negative anti-HAV antibody (aged 1 - 3 years) were taken for follow-up assay to observe seroconversion and geometric mean titre (GMT) level 2 months, 12 months, 6 years, and 10 years after inoculation. Another survey sampled from subjects of different age groups (3, 6, 9, 15, 18, 25 and 35 years) to compare anti-HA antibody positive rate before and after inoculation performed 10 years previously. Epidemiological observations were taken for 10 years to evaluate the relationship between vaccine coverage and hepatitis A morbidity. Serum antibody to HAV was detected by enzyme linked immunoassay (ELISA, calibrated by WHO international reference) and ABBOTT Axsym HAVAB microparticle enzyme immunoassay. RESULTS: Seroconversion in follow-up assay 2 months and 10 years after inoculation was 98.6% and 80.2% respectively. For children, the vaccination anti-HA antibody positive rates were significantly different before and after 10 years, 7.69% cf 70.45% (aged 3 years) and 52.58% cf 71.78% (aged 18 years). When vaccine coverage rose from 57% to 74%, there were no any HA epidemics. When vaccine coverage reached 85%, there were no any HA cases. With vaccine coverage between 85% and 91%, there were no any HA cases in cohorts from the age of 1 year to 15 years during the 10 years. CONCLUSIONS: Live attenuated hepatitis A vaccine has an obvious long-term effectiveness in prevention and control of HA epidemics through mass vaccination.