Improved prevention of perinatal hepatitis B transmission HBV by employing the Bio-Hep-B PreS1/PreS2/S HBV vaccine in new born babies from HBV positive mothers
Parasitology and Biology of Tropical Infectious Disease Pathogens
Final Report Abstract
The overall topic of trilateral project was to vaccinate babies, born to chronic hepatitis B virus (HBV) infected Arabic mothers, against HBV using the passive HBV vaccine (HBIG), but two different active HBV vaccines in local areas of Israel and Palestine and to further characterize breakthrough of viral mutants. The local PIs Prof. Dr. Rifaat Safadi at Hadassah Medical Center, Jerusalem/Israel and Dr. Maysa Azzeh, Al-Quds University, East Jerusalem-Abu Dies, Palestine managed the project in Israel and Palestine hospitals, respectively. Coordination and molecular virology of the project was covered by Dr. Dieter Glebe and Prof. Dr. Wolfram Gerlich (till his retirement in 2010) from Institute of Medical Virology at Justus-Liebig-University in Giessen/Germany. The efficacy of the conventional 2nd generation hepatitis B vaccine (e.g. Engerix-B) that contains only the S-HBs protein should be compared with a licensed 3rd generation preS1-, preS2-,and S-HBs-containing vaccine (BioHepB; now called Sci-B-Vac in Israel) in the newborn babies of HBsAg-positive mothers. This implies determination of the failure rate of vaccination in this particular setting by following the vaccinated children for at least one year to analyse HBV breakthrough rate and determination and characterization of HBV mutants in infected newborns. Although both partner sites recruited over 218 pregnant HBsAg-positive Arabic women to be included in the study, some mothers did not show up with their babies after one year for different reasons. The Israeli partner finally tested 60 newborns from the Engerix-B group and 28 of 60 from the Sci-B-Vac group at the age of one year. While up to 10% of children in the Engerix-B group were tested HBsAg-positive (possible vaccinebreakthrough), all 28 Sci-B-Vac tested children so far were negative in HBsAg test. Further serologic and molecular tests are underway to provide prove of these results. Further 30 Sci-B-Vac vaccinated children will be currently screened to get significant study groups. The Palestine partner found no proven viral breakthrough (HBsAg positivity) in the 36 of 51 newborns tested from the Engerix-B group and the 27 from 51 tested of the Sci-B-Vac group at the age of one year so far. However, similar to the Israeli partner, over 36 children will be tested within the next 6 months by the Palestinian side. In addition, the Palestinian partner was able to successfully establish a molecular virology lab for hepatitis B and analysed prevalence of HBV (sub)-genotypes of HBV carriers in Palestine. The German partner optimized the in vitro HBV infection system for testing neutralisation of HepB vaccine induced antisera (anti-HBs). The system was successfully expanded to both HBV and hepatitis delta virus (HDV) that used HBV surface proteins to infect susceptible hepatocytes. Besides primary hepatocytes, HBV and HDV-susceptible hepatoma cell lines were created that stably express the recently characterized high-affinity HBV-receptor “Sodium-dependent taurocholate cotransporting polypeptide (NTCP)”. Neutralisation of HBV and HDV pseudotyped with surface proteins of HBV genotype D (prevalent in Israel and Palestine) was evaluated in cell culture and showed complete neutralisation at 70 IU/L anti-HBs (German Engerix-B vaccinees), comparable with clinical observations. Since no HBV-containing human sera from vaccine-induced breakthrough were available from Israeli or Palestine partners so far, infectious HDV pseudoparticles harbouring several known HBV vaccine immune-escape mutants within the antigenic loop of HBV surface proteins (e.g. G145R) were generated by site-directed mutagenesis for further neutralisation studies. Although the program has formally ended, all partners agreed to continue and finalize open tasks of this successful Trilateral cooperation.
