An oral vaccine based on stable peptide-chitosan conjugate targeting DEC-205 for cancer immunotherapy

The development of oral vaccines faces significant challenges mainly due to the harsh gastrointestinal environment and low antigen-uptake efficiency. The gut-associated lymphoid tissue (GALT), particularly Peyer's patches (PPs), contains abundant immune cells, among which dendritic cells (DCs) serve as professional antigen-presenting cells (APCs) to initiate specific immune responses. In this study, we engineered an orally stable peptide DEBP-8 with high-affinity toward DEC-205, the endocytic receptor which can effectively mediate antigen uptake by intestinal DCs. This stable peptide was then conjugated to chitosan nanoparticles (CNPs) to design an oral vaccine, OVA@DEBP-8-CNP, encapsulating ovalbumin (OVA) as a model antigen. Harnessing the profiles of chitosan to activate STING pathway, this oral vaccine promotes DC maturation while targeting the endocytic receptor DEC-205 further enhances antigen uptake of the mature DCs. We demonstrated that OVA@DEBP-8-CNP accumulates in intestinal PPs, facilitates antigen cross-presentation to CD8⁺ T cells, and prevents tumor growth in B16-OVA tumor-bearing mice. The tumor-prevention effects of this oral vaccine are greatly impaired in PPs-deficient mice. To provide additional protection for CNP-encapsulated antigens in gastrointestinal tract, we employed microfluidic technology to coat CNPs within alginate microparticles (ALG MP), further improving the stability of the oral vaccine. This platform highlights the simplified design of DC-targeting oral vaccine for prevention of cancer and other diseases.