Chitin Micro-Particles (CMP): A Useful Adjuvant for Inducing Viral Specific Immunity when Delivered Intranasally with an HIV-DNA Vaccine

WE HAVE BEEN DEVELOPING an HIV-DNA vaccine based on an HIV-1 env and rev expression plasmid (20). Intranasal (i.n.) administration of this vaccine with an appropriate adjuvant induces high levels of antibody (Ab) production, especially secretory IgA (sIgA) Ab and HIV-specific cytotoxic T lymphocyte (CTL) activity in mice (7,23,31). HIV-specific sIgA Ab is an important aspect of vaccine design as it is effective at blocking HIV penetration of the mucosal membranes, which are the primary site for infection of several viruses including HIV. Our group and others have reported that mucosal IgA inhibits HIV-1 replication (3,8). A second component of a successful vaccine is the induction of strong CTL activity for the efficient elimination of virus-infected cells (6,30). An ideal HIV vaccine should be capable of inducing both strong mucosal and systemic CTL activity. Strong et al. reported that the intranasal application of chitin micro-particles (CMP) derived from shrimp or crab shells in mouse models of allergy markedly reduced allergic symptoms resulting from an up-regulation of IL-12, IFN-g and TNF-a (26). Shibata et al. indicated that chitin has a unique Th1 adjuvant effect on the development of immunity against a mycobacterial antigen (25). Other natural Th1 potentiators, such as heat-killed Brucella abortus or CpG immunostimulatory DNA sequences have proved very effective as vaccine adjuvants (10,13,32). The current study was designed to examine whether CMP has an adjuvant effect and whether this might be useful for nasal vaccination with HIV-DNA vaccine.