Oral immunization with acidified sucralfate@N-2-HACC/CMCS NPs elicits protective immune response in guinea pigs

Abstract

Oral administration of vaccine is required to preserve the vaccine against degradation, enhance antigen absorption in the gastrointestinal tract, and trigger adaptive immune responses. Nanomaterials are an ideal delivery vector for the creation of oral vaccines, and we have previously shown that N-2-hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC)/N,O-carboxymethyl chitosan (CMCS) based vaccine via oral administration led to protection against Newcastle disease virus. Hence, based on the immune adjuvant activity of N-2-HACC/CMCS nanoparticles and the advantage in resisting harsh gastric conditions of sucralfate acidified (SA), we constructed an oral vaccine delivery system based on SA and N-2-HACC/CMCS nanoparticles (SA@N-2-HACC/CMCS NPs), and the NPs were formulated to incorporate BSA. The SA@N-2-HACC/CMCS NPs had a particle size of 227 ± 7.0 nm and a zeta potential of 8.43 ± 2.62 mV. The NPs displayed slow and sustained release and high stability in simulated gastric juice and intestinal fluid. RAW 264.7 could better uptake the SA@N-2-HACC/CMCS/BSA NPs. The vaccine via oral administration markedly enhanced the residence time of BSA in the intestine for more than 12 h and elicited the production of IgG and sIgA. The SA@N-2-HACC/CMCS NPs developed here for oral administration is an excellent technique for delivering antigens and provides a path of mucosal vaccine research.