Intramuscular delivery of a plasmid-encoded molecular adjuvant elicits immune responses at mucosal sites in a macaque model (39.51)

Abstract

As the primary site of HIV-1 replication is the mucosa, a desirable feature of a HIV-1 vaccine would be the generation of immune responses at mucosal sites. We created an optimized CCL27 DNA construct as well as optimized SIV gag, pol, and env plasmids for immunizing rhesus macaques. Macaques (n=5/group) were immunized with SIV plasmids +/- CCL27. Both immunization groups had significant IFN-g responses against the encoded SIV antigens (~12,000 SFU/106 PBMCs). CD8+ T cell proliferation as measured by CFSE staining was similar between the groups at ~22%. While systemic immune responses were robust, co-delivery of CCL27 did not adjuvant peripheral responses similar to what was observed in mice. Interestingly, macaques that received CCL27 had greater antigen specific IgA at mucosal sites including bronchial lavage and fecal samples. In addition, CD4+ T cells secreting effector cytokines were enhanced in the CCL27 group at mucosal, but not peripheral sites when compared to the antigenic group alone. The CCL27 group also had more polyfunctional CD8+ T cells in the bronchial lavage than the DNA group post-challenge. These data show that a novel chemokine adjuvant may be capable of targeting immune responses to mucosal sites. This strategy may also be applicable to other diseases than HIV-1 where mucosal immune responses are desirable.