Novel hepatitis B vaccines.

Currently available hepatitis B vaccines are immunogenic, efficacious and safe. There is no doubt that their consistent use makes the elimination of hepatitis B in most countries possible. Nevertheless, there are still aspects of these vaccines which could be improved: three doses are needed for a full course of vaccination (which is sometimes difficult to achieve because of poor compliance or difficult logistic situations in some regions), there is a comparably high rate of non-responders to the vaccine (about 5% in adults) and, finally, it is not impossible that there are strains of HBV showing mutations of HBsAg which could escape the immunity induced by present vaccines. Work is underway to overcome these problems. Combined vaccines such as those providing protection against diphtheria, pertussis, tetanus, Haemophilus influenzae type b hepatitis B and poliomyelitis are an important step in simplifying hepatitis B vaccination of infants. Combined vaccines are already in use under clinical evaluation. In an effort to reduce the number of injections, two dose schedules with vaccines of higher dosages are being examined and single-dose vaccines encapsulated in degradable micro-particles of biopolymers (called slow-release vaccines) have been successfully tested in animals. Intense research is being conducted to enhance the immunogenicity of present vaccines. One possibility under investigation is the development of recombinant vaccines containing the complete preS1 and preS2 regions of HBsAg or immunogenic epitopes of these regions in addition to the small surface protein; several of such vaccines have already been tested in clinical trials. Future developments include expression of HBsAg determinants in bacteria, e.g., Salmonella, for oral vaccination or DNA vaccines against hepatitis B.