Non-replicating recombinant vaccinia virus encoding murine B-7 molecules elicits effective costimulation of naive CD4+ splenocytes in vitro

Abstract

Using a series of new insertion/expression vectors, we constructed a set of recombinant vaccinia viruses (recVV) encoding the murine T cell costimulatory molecules mB7-1 or mB7-2, or both together in the same construct. On infection with replication incompetent and non-cytopathic recVV, several tumour cell lines expressed the respective molecules and bound to CTLA-4. The highest binding capacity was found when both mB7 molecules were co-expressed. Mouse B16.F10 melanoma cells expressing mB7-1 or mB7-2 provided effective costimulation for proliferation of resting CD4+ T cells in the presence of concanavalin A and plate-bound anti-T cell receptor antibodies, respectively. If mB7-1 and mB7-2 were delivered together on the same cell, the proliferative response of CD4+ T cells increased further. The costimulatory effect could be blocked with CTLA-4, the soluble ligand for B7 molecules. The possibility of engineering tumour cells using recVV holds implications for the future design of vaccination strategies.