Modulation of immunity against herpes simplex virus infection via mucosal genetic transfer of plasmid DNA encoding chemokines

In this study, we examined the effects of murine chemokine DNA as genetic a djuvants given mucosally, on the systemic and distal mucosal immune respons es to plasmid DNA encoding gB of herpes simplex virus (HSV) by using the mo use model. The CC chemokines macrophage inflammatory protein 1 beta (MIP-1 beta) and monocyte chemotactic protein 1 (MCP-1) biased the immunity to the Th2-type pattern as judged by the ratio of immuno globulin isotypes and in terleukin-4 cytokine levels produced by CD4(+) T cells. The CXC chemokine M IP-2 and the CC chemokine MIP-1 alpha, however, mounted immune responses of the Th1-type pattern, and such a response rendered recipients more resista nt to HSV vaginal infection. In addition, MIP-1 alpha appeared to act via t he upregulation of antigen-presenting cell (APC) function and the expressio n of costimulatory molecules (B7-1 and B7-2),whereas MIP-2 enhanced Th1-typ e CD4(+) T-cell-mediated adaptive immunity by increasing gamma interferon s ecretion from activated NK cells. Our results emphasize the value of using the mucosal route to administer DNA modulators such as chemokines that func tion as adjuvants by regulating the activity of innate immunity. Our findin gs provide new insight into the value of CXC and CC chemokines, which act o n different innate cellular components as the linkage signals between innat e and adaptive immunity in mucosal DNA vaccination.