The use of combination vaccinia vaccines and dual-gene vaccinia vaccines to enhance antigen-specific T-cell immunity via T-cell costimulation

Several recombinant vaccinia viruses are currently being evaluated to induc e antigen-specific immunity to a variety of infectious disease agents and t umor associated antigens. T-cell costimulation is extremely important in en hancing T-cell responses, and recombinant vaccines have now been shown to b e effective vectors to express a range of these molecules. Both combination vaccines (an admixture of a recombinant vaccinia virus expressing a specif ic target antigen and a recombinant vaccinia virus expressing a costimulato ry molecule) and dual-gene vaccines expressing both transgenes on the same vector have been shown capable of effectively enhancing antigen-specific re sponses via T-cell costimulation. In this report, we compare for the first time the use of both types of approaches to enhance antigen-specific T-cell responses, and we demonstrate the importance of route of vaccine administr ation and vaccine dose in attaining optimal T-cell responses. These studies should have direct bearing on the design of vaccine clinical trials for in fectious agents and/or tumor associated antigens, in which T-cell costimula tory molecules will be employed to enhance antigen-specific T-cell response s via the use of either combination or dual-gene vaccinia vaccines. (C) 199 9 Elsevier Science Ltd. All rights reserved.