Curdlan sulfate&ndash;<em>O</em>-linked quaternized chitosan nanoparticles: potential adjuvants to improve the immunogenicity of exogenous antigens via intranasal vaccination

Abstract

IntroductionThe development of ideal vaccine adjuvants for intranasal vaccination can provide convenience for many vaccinations. As an ideal intranasal vaccine adjuvant, it should have the properties of assisting soluble antigens to pass the mucosal barrier and potentiating both systemic and mucosal immunity via nasal administration.MethodsBy using the advantages of polysaccharides, which can promote both T-helper 1 and 2 responses, curdlan sulfate (CS)–O-(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride (O-HTCC) nanoparticles were prepared by interacting CS with O-HTCC, and the adjuvancy of the nanoparticles was investigated.ResultsThe results showed that the polysaccharide-based nanoparticles induced the proliferation and activation of antigen-presenting cells. High protein-loading efficiency was obtained by testing with the model antigen ovalbumin (Ova), and the Ova adsorbed onto the cationic CS/O-HTCC complexes was taken up easily by the epithelium. To evaluate the capacity of the Ova/CS/O-HTCC nanoparticles for immune enhancement in vivo, we collected and analyzed immunocytes, serum, and mucosal lavage fluid from intranasally vaccinated mice. The results showed that Ova/CS/O-HTCC nanoparticles induced activation and maturation of antigen-presenting cells and provoked the proliferation and differentiation of lymphocytes more significantly compared to the immunization of Ova mixed with aluminum hydroxide gel. Furthermore, CS/O-HTCC evoked a significantly higher level of Ova-specific antibodies.ConclusionTherefore, these results suggest that CS/O-HTCC nanoparticles are ideal vaccine adjuvants for soluble antigens used in intranasal or mucosal vaccination.

Nanoparticle-Based Vaccines Against Respiratory Viruses

“…This observation correlated closely with the reduced lung pathology and the substantial clearance of the virus from the animal lungs. Other polymeric nanoparticles, such as chitosan, a natural polymer composed of randomly distributed β-(1-4)-linked d-glucosamine and N-acetyl-d-glucosamine, and N-(2-hydroxypropyl)methacrylamide/N-isopropylacrylamide (HPMA/NIPAM), were also investigated as intranasal vaccines against respiratory viruses (85)(86)(87)(88)(89)(90)(115)(116)(117)(118)(119)(120)(121). Overall, polymeric nanoparticles have many advantages, including biocompatibility (122), antigen encapsulation and stabilization (123,124), controlled release of antigens and intracellular persistence in APCs (125,126), pathogen-like characteristics, and suitability for intranasal administration (126,127).…”

Lower-Sized Chitosan Nanocapsules for Transcutaneous Antigen Delivery

“…The antigen association in the shell of nanocapsules allows a fast recognition by immunocompetent cells and therefore it is expected that it would trigger an efficient immune response. Other nanoformulations have shown similar or lower OVA loading efficiency in comparison to our CSNCs [ 40 , 41 ].…”

Advancements in prophylactic and therapeutic nanovaccines

“…Studies by Swaminathan et al, have proved enhanced immune responses by lipid nanoparticle (LNP) adjuvant formulations against ovalbumin (OVA) and hepatitis B virus surface antigen (HBsAg) in BALB/c and C57BL/6 mice injected with HBsAg along with LNPs as compared to HBsAg alone [52] . Co-administration of quarternized chitosan nanoparticles as adjuvants along with ovalbumin intranasally in female BALB/c mice induced activation of APCs followed by enhanced lymphocyte proliferation and differentiation as compared to OVA mixed with aluminum hydroxide gel [53] . Asgary et al, also reported that silver nanoparticles showed increased antibodymediated responses against CVS-11 rabies and reduced toxicity as compared to conventionally used adjuvants such as alum [54] .…”