5  Antiviral nanomaterials and delivery systems of polysaccharides
Nanobiotechnology provides a variety of solutions for the prevention, diagnosis, and treatment of infectious diseases such as viruses. Nanoparticles can be designed as an efficient delivery system to increase the activity of low toxicity vaccines against the host [125]. The application of nanoparticles in vaccine formulations can not only improve the immunogenicity and stability of antigen, but also achieve targeted delivery and sustained release [126]. Nanomaterials may have intrinsic immunomodulatory functions, acting as adjuvants or immune potentiators [127]. The chitosan/alginate nanoparticle encapsulated bee venom (BV) with slow-releasing properties and mucosal adhesiveness has been developed, which can effectively induce non-specific immune stimulation, particularly those related to Th1 responses and viral clearance activities against PRRSV infection [128]. The effectiveness of a novel nanoparticle vaccine is supported by stimulating effective neutralizing antibody and antigen-specific T cell responses in mice immunized with a MERS-CoV nanoparticle vaccine candidate. Using a MERS-CoV-permissive transgenic mouse model, it is shown that the mice immunized with this nanoparticle-based MERS-CoV vaccine can protect against a lethal challenge of MERS-CoV without triggering undesirable eosinophilic immunopathology. The biocompatible hollow nanoparticle may accelerate the development of effective and safe vaccines against emerging coronavirus pathogens [129]. Bovine coronavirus (BCV) N protein-loaded chitosan nanoparticles (CNP) can significantly increase both IgA and IgG levels after the second immunization comparable to the control group. The IgM content in serum increased after the second immunization in the BCV N protein-loaded CNP group. These findings indicate that CNP can be used as a novel adjuvant in veterinary vaccine field [130].
In addition, the gold nanoparticles (AuNPs)-based nanomaterials also have good application prospects in anti-novel coronavirus. An electrochemical immunosensor based on an array of AuNPs-modified carbon electrodes was used for the determination of MERS-CoV (Fig. 8 ) [131]. Highly sulfonated gold nanoparticles and heparin coated AuNPs with no cytotoxicity displayed broad-spectrum virucidal properties against HSV, HPV, RSV, dengue and lentivirus in vitro [132]. S protein plays a key role in the pathogenesis of coronavirus, and it is considered a primary target for vaccine preparation [8,133]. Virus like particles (sVLPs) were prepared by protein corona formation with IBV S protein as a model antigen and incubated with 100 nm AuNPs in a solution containing an optimized concentration of viral proteins [133]. As compared to inoculation with free proteins, vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-associated symptoms in an avian model of coronavirus infection [133]. The study demonstrates a simple and reliable method in bridging viral antigens with synthetic nanoparticles for improved vaccine application [133].
Fig. 8 COV immunosensor array chip (a). The immunosensor fabrication steps (b), the detection process of the competitive immunosensor for the virus (c) [131].
Additionally, polysaccharides or their derivatives, such as carrageenan oligosaccharide and fucoidan derived from marine algae with biodegradability, abundance, and non-toxicity, can be used as biocompatible reductants for green synthesis AuNPs [134,135]. Based on our previous works, we hypothesize that the S or N protein from coronavirus can be designed to be loaded onto polysaccharides capped AuNPs by protein corona formation for coronavirus nanoparticles vaccine application (Fig. 9 ).
Fig. 9 The proposed schematics illustrating the S or N protein from coronavirus loaded onto polysaccharides capped AuNPs.