Chitosan Nanoparticle Encapsulated Hemagglutinin-Split Influenza Virus Mucosal Vaccine

Abstract

Abstract. Subunit/split influenza vaccines are less reactogenic compared with the whole virus vaccines. However, their immunogenicity is relatively low and thus required proper adjuvant and/or delivery vehicle for immunogenicity enhancement. Influenza vaccines administered intramuscularly induce minimum, if any, mucosal immunity at the respiratory mucosa which is the prime site of the infection. In this study, chitosan (CS) nanoparticles were prepared by ionic cross-linking of the CS with sodium tripolyphosphate (TPP) at the CS/TPP ratio of 1:0.6 using 2 h mixing time. The CS/TPP nanoparticles were used as delivery vehicle of an intranasal influenza vaccine made of hemagglutinin (HA)-split influenza virus product. Innocuousness, immunogenicity, and protective efficacy of the CS/TPP-HA vaccine were tested in influenza mouse model in comparison with the antigen alone vaccine. The CS/TPP-HA nanoparticles had required characteristics including nano-sizes, positive charges, and high antigen encapsulation efficiency. Mice that received two doses of the CS/TPP-HA vaccine intranasally showed no adverse symptoms indicating the vaccine innocuousness. The animals developed higher systemic and mucosal antibody responses than vaccine made of the HA-split influenza virus alone. The CS/TPP-HA vaccine could induce also a cell-mediated immune response shown as high numbers of IFN-γ-secreting cells in spleens while the HA vaccine alone could not. Besides, the CS nanoparticle encapsulated HA-split vaccine reduced markedly the influenza morbidity and also conferred 100% protective rate to the vaccinated mice against lethal influenza virus challenge. Overall results indicated that the CS nanoparticles invented in this study is an effective and safe delivery vehicle/adjuvant for the influenza vaccine.

Synthetic Nanoparticles for Vaccines and Immunotherapy

“…Furthermore, chitosan nanoparticles conferred 100% protection against lethal intranasal influenza challenge. 182 Bal et al undertook a comprehensive study of the humoral effects of immunomodulators when co-encapsulated with antigen in chitosan nanoparticles in intranasal or intradermal vaccination models. As expected, nanoparticulate antigen induced stronger antibody responses regardless of immunization route, but the potency of immunomodulators—CpG, lipopolysaccharide, PAM 3 CSK 4 , muramyldipeptide, and cholera toxin subunit B—was dependent on the immunization route.…”

Designing self-assembled peptide nanovaccine against Streptococcus pneumoniae: An in silico strategy

“…In this regard, the sequences 271-290, and 331-350 were selected as universal T-helper epitopes in our study. The efficacy of nanovaccines were confirmed in different investigations, including influenza nanovaccine [57], chitosan nanoparticle against H1N1 influenza virus [58], and chaitosan-formulated polyepitope vaccine against pulmonary mycobacterial [59]. Another important approach for increasing the immunogenicity of peptide vaccine is the use of self-assembled peptide structures, including alpha helical or beta sheet motifs, which can obtain from natural or de novo structures.…”

Nanoengineering of vaccines using natural polysaccharides

“…After intranasal administration of hemagglutinin-loaded chitosan nanoparticles to mice, both the systemic and mucosal antibody levels (IgG and IgA) were significantly enhanced with respect to the controls (antigen in solution), and a T cell response was also reported. Importantly, after being challenged through the same route with the virus, the animals receiving the nanovaccine presented higher survival rates (Sawaengsak et al, 2014). In another study, chitosan nanoparticles were loaded with Streptococcus equi bacterial proteins and administered intranasally to mice.…”