Cryogel vaccines effectively induce immune responses independent of proximity to the draining lymph nodes

The delivery location of traditional vaccines can impact immune responses and resulting efficacy. Cryogel-based cancer vaccines, which are typically injected near the inguinal lymph nodes (iLNs), recruit and activate dendritic cells (DC) in situ, induce DC homing to the iLNs, and have generated potent anti-tumor immunity against several murine cancer models. However, whether cryogel vaccination distance to a draining LN affects the kinetics of DC homing and downstream antigen-specific immunity is unknown, given the heightened importance of the scaffold vaccine site. We hypothesized that vaccination near the iLNs would lead to more rapid DC trafficking to the iLNs, thereby inducing faster and stronger immune responses. Here, mice were injected with cryogel vaccines against ovalbumin either adjacent or distal to the iLNs, and the resultant DC trafficking kinetics, T cell phenotypes, antigen-specific T cell and humoral responses, and prophylactic efficacy in an ovalbumin-expressing tumor model were assessed. Cryogel vaccines induced potent, long-lasting antigen-specific immune responses independent of distance to the iLNs, with no significant differences in DC trafficking kinetics, ovalbumin-specific T cell and antibody responses, or prophylactic efficacy. Moreover, DC trafficking and activation state were not impacted when cryogels were injected near a tumor. These results demonstrate a flexibility in vaccination location for scaffold-based vaccines, independent of draining LN distance.