The aim of this proposal is to develop a safe and effective attenuated poxvirus-vectored measles vaccine for use in infants less than one year of age. Two highly attenuated poxvirus vectors, NYVAC and ALVAC, have been developed and characterized to specifically address issues of safety in large scale vaccination programs. These vectors will be used to determine the optimal constellation of measles virus antigens required to induce both humoral and cell-mediated immune responses. lmmunogenicity of candidate vaccines will be assessed by evaluating functional responses in laboratory animals and by determining that co- expression of particular combinations of antigens does not lead to aberrant immune responses. This pre-clinical information will be essential to evaluate potential measles vaccine candidates to be used in Phase 1 human trials. A close structural and serological relationship exists between measles virus and canine distemper virus. In order to establish that the canine distemper virus system can be used as a model to evaluate measles virus vaccine candidates, we will develop NYVAC and ALVAC-based CDV recombinants for a parallel evaluation of immunogenicity in laboratory animals. Safety, immunogenicity, and protective efficacy will then be evaluated in young pups in the absence of maternal antibody. We will use the information derived from these studies to select the NYVAC and ALVAC- based recombinants expressing the optimal combination of canine distemper virus antigens. These recombinants will then provide the tools to address, in an efficacy trial in the target species, the critical question of the effect of maternal antibody on the outcome of vaccination of young pups with a pox-vectored vaccine.
