S V ADENOVIRUS RECOMBINANTS FOR VACCINE EFFICACY

A MODEL VACCINE SYSTEM WILL BE DEVELOPED USING RECOMBINANT DNA TECHNOLOGY AND CLASSIC VIROLOGY TO CONSTRUCT A NONDEFECTIVE RECOMBINANT ADENOVIRUS THAT EXPRESSES THE SIMIAN IMMUNODEFICIENCY VIRUS (SIV) ENVELOPE PROTEIN. VACCINATION OF RHESUS MACAQUES WITH THE RECOMBINANT SIV-ADENOVIRUS AND SUBSEQUENT CHALLENGE WITH SIV WILL PROVIDE IMPORTANT INFORMATION CONCERNING IMMUNOLOGIC RESPONSES AND THE EXTENT OF PROTECTION THAT CAN BE APPLIED IN THE DEVELOPMENT OF AN ANALOGOUS VACCINE DIRECTED AGAINST HIV. IT IS PLANNED TO CLONE A MACAQUE ISOLATE OF SIV AS A SOURCE OF ENVELOPE GENE CODING SEQUENCES THAT WILL BE INSERTED INTO A PREVACCINE VECTOR AND EXPRESSED UNDER TRANSCRIPTIONALCONTROL OF THE ADENOVIRUS MAJOR LATE PROMOTER. THE SIV ENVELOPE CODING SEQUENCES WILL BE INCORPORATED INTO A HUMAN ADENOVIRUS BY RECOMBINATION IN CULTURED CELLS BETWEEN THE PREVACCINE PLASMID VECTOR AND ADENOVIRUS 2 DNA. THE PRESENCE OF SV40 T ANTIGEN SEQUENCES IN THE PLASMID CONSTRUCT WILL MAKE IT POSSIBLE TO OBTAIN A RECOMBINANT HUMAN ADENOVIRUS THAT REPLICATES EFFICIENTLY IN MONKEY CELLSAND CAN BE USED FOR VACCINE SAFETY AND EFFICACY TRIALS IN RHESUS MACAQUES. THIS APPROACH SHOULD MAKE IT FEASIBLE TO EVALUATE THE USEFULNESS OF VARIOUS CANDIDATE VACCINE FORMATSAND IMMUNIZATION PROTOCOLS.