Enhanced Immune Responses to Mucosa by Functionalized Chitosan-Based Composite Nanoparticles as a Vaccine Adjuvant for Intranasal Delivery

Abstract

Nasal administration for vaccine delivery is a novel non-invasive vaccine administration approach that can induce local or systemic immune responses and overcome the disadvantages caused by traditional injectable administration. However, mucosal vaccine and adjuvant delivery systems with sustained-release ability and enhanced immune effects at mucosal sites have still been highly demanded. In this work, N-2-hydroxypropyl trimethyl ammonium chloride chitosan/N,O-carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS NPs) with excellent mucosal absorption, high drug loading capacity, and enhanced immune responses were prepared by the ionic cross-linking method. To evaluate the potential capacity of the N-2-HACC/CMCS NPs as a vaccine adjuvant and the molecular mechanism for the induction of enhanced mucosal and systemic immune responses, bovine serum albumin (BSA) was employed as a general model antigen and loaded into the N-2-HACC/CMCS NPs to prepare a BSA-loaded N-2-HACC/CMCS adjuvant vaccine (N-2-HACC/CMCS/BSA NPs). It was well demonstrated that the N-2-HACC/CMCS/BSA NPs with great biostability and mucosal absorption could effectively promote the proliferation of lymphocytes and the secretion of related pro-inflammatory factors, resulting in the stimulation of specific mucosal and systemic immune responses. This study revealed that the chitosan-based nano-delivery system can act as the mucosal vaccine adjuvant and possesses great promise in viral infectious diseases and immunization therapy.

Nanoemulsions and nanocapsules as carriers for the development of intranasal mRNA vaccines

“…As detailed Table 2, different polymers were explored, including protamine (PR), dextran sulphate (DX), chitosan (CS) and PEG-PGA (PP), aiming to modify the surface of the nanocarriers and enhance their uptake by dendritic cells and, hence, their immunogenic properties. These polymers have previously been used as adjuvant and antigen delivery systems, capable of activating different T and B cell responses [28][29][30][31][32]. NE-mRNAs were prepared using two distinct strategies.…”

Polymeric Nanoparticles for Drug Delivery

“…791,792 To evaluate the adjuvant properties and mucosal immune response of chitosan derivative nanoparticles, Zhao and co-workers developed bovine serum albumin (BSA)loaded N-2-hydroxypropyl trimethyl ammonium chloride chitosan/N,O-carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS/BSA NPs). 793 Both in vitro and in vivo studies revealed enhanced BSA antigen uptake in dendritic cells for these chitosan nanoparticles, as opposed to the antigen alone. The nanoparticles exhibited prolonged antigen retention in mucosal tissues even after 8 h post immunization, confirming the antigen-protective quality of the nanoparticle.…”

“…Thus, chitosan is often modified with other functional groups to overcome this solubility problem, thereby enhancing its effectiveness as a mucosal vaccine strategy. Nanoparticles prepared from chitosan derivatives are some of the most promising designs to enhance mucosal immunity. , To evaluate the adjuvant properties and mucosal immune response of chitosan derivative nanoparticles, Zhao and co-workers developed bovine serum albumin (BSA)-loaded N -2-hydroxypropyl trimethyl ammonium chloride chitosan/ N , O -carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS/BSA NPs) . Both in vitro and in vivo studies revealed enhanced BSA antigen uptake in dendritic cells for these chitosan nanoparticles, as opposed to the antigen alone.…”

Chitosan: A Potential Biopolymer in Drug Delivery and Biomedical Applications

“…Using the ionic crosslinking method, Lin et al developed a chitosan nanoparticle system with high antigen loading and mucosal absorption capacity for sustained immunization effect. Using bovine serum albumin as a model antigen, the authors demonstrated that the particles with excellent biostability and mucosal absorption could efficiently stimulate the proliferation of lymphocytes and the release of associated pro-inflammatory substances, therefore stimulating particular mucosal and systemic immune responses when administered nasally [261].…”