Chitosan hydrogel vaccine generates protective CD8 T cell memory against mouse melanoma

Abstract

CD8(+) T cells are important in the control of viral infections and cancers because of their cytolytic activity. A vaccine able to generate these cells could be beneficial in the prevention or treatment of these diseases. Chitosan hydrogel is a promising vaccine formulation that has previously been shown to generate effector CD8(+) T cells in a mouse model. This vaccine promotes sustained release of antigen and adjuvant, which generates a robust effector response. For longer lasting immunity, a memory population of these CD8(+) T cells is required to control further disease. We found that vaccination with chitosan hydrogel or dendritic cells using ovalbumin protein as a model antigen and Quil-A adjuvant provided protection in a subcutaneous melanoma challenge 30 days later. Ovalbumin-specific memory CD8(+) T cells were detectable following vaccination with the chitosan hydrogel but not the dendritic cell vaccine and an in vivo cytotoxicity assay demonstrated specific lysis of target cells in chitosan hydrogel vaccinated mice but not those receiving dendritic cell vaccination. These results demonstrate that vaccination with chitosan hydrogel is equally effective as dendritic cell vaccination in tumour protection but has more readily detectable immune correlates of protection. This may be advantageous in predetermining protection in vaccinated individuals.

Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines

“…The pentablock copolymer hydrogels with their increased stability and sustained release of antigen and immunomodulators stimulated strong, long-lasting T cell and antibody responses. These results are in agreement with the recent investigations on chitosan thermoresponsive hydrogels as sustained vaccine delivery systems; however, those systems had less than optimal formulation characteristics (36,43). Interestingly, the inclusion of PLGA-NP in the hydrogels delayed the induction of both cellular and humoral immune responses, possibly due to the reduced burst release and overall slower release of vaccine components.…”

Evaluation of hydrophobic chitosan-based particulate formulations of porcine reproductive and respiratory syndrome virus vaccine candidate T cell antigens

“…Chitosan was selected as the polymer core of the particulate vaccines due to its inherent immunostimulatory properties (Highton et al, 2015;Zaharoff et al, 2007;Zhu et al, 2007), which is thought to be mediated through engagement of TLR4 and mannose receptors on antigen-presenting cells (Villiers et al, 2009). Rather unexpectedly, the results of the in vitro evaluation of our chitosan particles showed that non-adjuvanted particles failed to induce cytokine responses from porcine DCs and elicited only an IL-8 response from monocytes.…”

Biodegradable polymers for modern vaccine development

“…Chitosan hydrogels are a sustained-release vaccine delivery system, primarily consisting of the naturally occurring polymer chitosan [26]. Chitosan solutions can be altered by the addition of polyol salts to be thermosensitive, such that the hydrogels are only formed at body temperature.…”