Najibi, Shih, and Mooney vaccinated OVA+ tumor-bearing and control mice with blank cryogel or cryogel-based vaccine(s) comprising OVA protein and GM-CSF with or without CpG. DC activation and migration to the cryogel OVA+ vaccine and draining inguinal (d)LN were not impacted by the presence of tumor, nor adjacency of the s.c. vaccination site to the dLN. The T cell phenotypes and the potency, character, and kinetics/longevity of the OVA-specific CD8+ T cell and antibody responses generated in the blood, LNs, and/or spleen, and the prophylactic efficacy in an OVA+ melanoma model were shown to be independent of vaccination proximity to the dLN.
Contributed by Paula Hochman
ABSTRACT: 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.
Author Info: (1) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering at Harvard Unive
Author Info: (1) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. (2) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. (3) John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA. Electronic address: mooneyd@seas.harvard.edu.
