NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses

Although poxvirus vectors are widely used in preclinical and clinical trials as candidate vaccines for multiple pathogens, how these vectors affect the host immune response is not clear. In this study, we developed a poxvirus vector based on the attenuated New York vaccinia virus (NYVAC), which is able to target a central host-cell signaling pathway, NFκB. In mice, the modified NYVAC acts on the immune system by increasing specific neutrophil migration via NFκB activation and in turn enhances CD8 T-cell responses to HIV antigens delivered by the viral vector. We show that these inherent properties define a mechanism for poxvirus-induced immune responses and offer novel approaches to vaccine vector design.