The goal of this proposal is to develop safe and effective poxvirus-based human T-cell lymphotropic virus type I (HTLV-I) vaccine candidates. Our laboratory has developed two highly attenuated poxvirus vectors appropriate for administration to humans; NYVAC and ALVAC. These vectors will be used to generate a series of poxvirus recombinants expressing the HTLV-I env, gag-pol and/or pX gene products. The immunogenicity of these recombinants will be evaluated in two animal systems, rabbits and rhesus macaques, while efficacy will be assessed in HTLV-I challenge studies in rabbits. We will also evaluate prime/boost immunization regimens, whereby primary immunization with a poxvirus/HTLV-I recombinant is followed by a boost with purified HTLV-I envelope glycoprotein or defective HTLV-I particles (pseudovirions). These studies will indicate which combination of HTLV-I antigens and which immunization regimen is most immunogenic and efficacious. These studies will also establish a database upon which potential phase I human trials will be based.
