SELECTIVE INDUCTION OF IMMUNE-RESPONSES BY CYTOKINES COEXPRESSED IN RECOMBINANT FOWLPOX VIRUS

Avipoxviruses have recently been studied as potential vectors for the delivery of heterologous vaccine antigen. Because these viruses aborti vely infect mammalian cells yet still effectively present encoded fore ign genes to the host immune system, they offer a safer but effective alternative to other live virus vectors. We have examined the effect o f coexpressing the cytokine interleukin-6 or gamma interferon on immun e responses to a recombinant fowlpox virus expressing influenza virus hemagglutinin. The encoded cytokine was expressed for prolonged period s in infected cell culture with little cytopathic effect due to the ab ortive nature of the infection. In mice, vector-expressed cytokine dra matically altered immune responses induced by the coexpressed hemagglu tinin antigen. Expression of interleukin-6 augmented both primary syst emic and mucosal antibody responses and primed for enhanced recall res ponses. In contrast, expression of gamma interferon markedly inhibited antibody responses without affecting the generation of cell-mediated immunity. The safety of these constructs was demonstrated in mice with severe combined immunodeficiency, and no side effects due to cytokine expression were observed. In summary, fowlpox virus vectors encoding cytokines represent a safe and effective vaccine strategy which may be used to selectively manipulate the immune response.