Interplay of cytokines and adjuvants in the regulation of mucosal and systemic HIV-specific CTL

We examined the interplay between cytokines and adjuvants to optimize the i nduction of CTL by a mucosal HIV peptide vaccine. We show synergy between I L-12 and GM-CSF when administered together with the HIV peptide PCLUS3-18II IB and cholera toxin (CT) in the induction of CTL activity and protection a gainst mucosal viral transmission, Further, we examine the efficacy of muta nt Escherichia coli labile toxin, LT(R192G), as a less toxic adjuvant than CT. LT(R192G) was as effective as or more effective than CT at inducing a m ucosal CTL response. Moreover, LT(R192G) was as effective without IL-12 as CT was when combined with IL-12, and the response elicited by LT(R192G) wit h the vaccine was not further enhanced by the addition of IL-12. GM-CSF syn ergized,vith LT(R192G) without exogenous IL-12, Therefore, LT(R192G) may in duce a more favorable cytokine response by not inhibiting IL-12 production, In particular, less IL-4 is made after LT(R192G) than CT immunization, and the response is less susceptible to anti-IL-12 inhibition. Thus, the choic e of mucosal adjuvant affects the cytokine environment, and the mucosal res ponse and protection can be enhanced by manipulating the cytokine environme nt with synergistic cytokine combinations incorporated in the vaccine.