The HVS in collaboration with SmithKline Beecham, Rixensart, Belgium, has developed several candidate live attenuated HAV vaccines. In addition, the HVS has developed a candidate recombinant hepatitis E vaccine that is highly promising and that is currently in clinical trials. The HVS is studying the technology of DNA vaccines with a model system based upon hepatitis B virus (HBV) vaccine, a vaccine with which the HVS has had extensive experience. We are currently testing the efficacy of an immunostimulant (CpG) as an adjuvant for DNA vaccines, as well as for protein vaccines. In addition, the utility of DNA vaccines for the control of hepatitis C virus (HCV) is being explored. These studies were extended to non-human primates (rhesus monkeys and chimpanzees). A DNA vaccine proved to be highly immunogenic in mice and rhesus monkeys and moderately immunogenic in chimpanzees, but the chimpanzees were not fully protected when they were challenged with live HCV.Passive immunoprophylaxis has also been an important public health tool. For example, normal immunoglobulin has been important in the prevention of hepatitis A. However, monoclonal preparations could be more potent, tailored to specific neutralization epitopes and highly consistent in potency. We have prepared combinatorial libraries from the bone marrow of chimpanzees that had been experimentally infected in sequence with each of the five human hepatitis viruses. Chimpanzee globulins are virtually identical to human immunoglobulins, making them attractive choices for immunoprophylactic and immunotherapeutic agents.
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