A global vaccination strategy must take into account production and delivery costs as well as efficacy and safety. A heat-stable,
polyvalent vaccine that requires only one inoculation and induces a high level of humoral and cellular immunity against several diseases is therefore desirable. A new approach is to use live microorganisms such as mycobacteria, enteric bacteria, adenoviruses, herpesviruses and poxviruses as
vaccine vectors. A potential limitation of live
polyvalent vaccines, however, is existing immunity within the target population not only to the vector, but to any of the expressed
antigens. This could restrict replication of the vector, curtail expression of
antigens, and reduce the total immune response to the
vaccine. Recently acquired immunity to vaccinia virus can severely limit the efficacy of a live recombinant
vaccinia-based
vaccine, so a strategy involving closely spaced inoculations with the same vector expressing different
antigens may present difficulties. We have constructed a recombinant vaccinia virus that expresses
surface proteins from two diverse pathogens, influenza A virus haemagglutinin and herpes simplex virus type 1 (HSV-1)
glycoprotein D. Mice that had recently recovered from
infection with either HSV-1 or influenza A virus could still be effectively immunized with the double recombinant.