Immune response by nasal delivery of hepatitis B surface antigen and codelivery of a CpG ODN in alginate coated chitosan nanoparticles

Abstract

Alginate coated chitosan nanoparticles were previously developed with the aim of protecting the antigen, adsorbed on the surface of those chitosan nanoparticles, from enzymatic degradation at mucosal surfaces. In this work, this new delivery system was loaded with the recombinant hepatitis B surface antigen (HBsAg) and applied to mice by the intranasal route. Adjuvant effect of the delivery system was studied by measuring anti-HBsAg IgG in serum, anti-HBsAg sIgA in faeces extracts or nasal and vaginal secretions and interferon-gamma production in supernatants of the spleen cells. The mice were primed with 10 microg of the vaccine associated or not with nanoparticles and associated or not with 10 microg CpG oligodeoxynucleotide (ODN) followed by two sequential boosts at three week intervals. The association of HBsAg with the alginate coated chitosan nanoparticles, administered intranasally to the mice, gave rise to the humoral mucosal immune response. Humoral systemic immune response was not induced by the HBsAg loaded nanoparticles alone. The generation of Th1-biased antigen-specific systemic antibodies, however, was observed when HBsAg loaded nanoparticles were applied together with a second adjuvant, the immunopotentiator, CpG ODN. Moreover, all intranasally vaccinated groups showed higher interferon-gamma production when compared to naïve mice.

Intranasal Drug Delivery: How, Why and What for?

“…However, human nasal vaccination is not restricted to the upper airways affections. After nasal immunization secretory immunoglobulin A can also be detected in other mucosal secretions, which may be important against virus transmitted through other mucosal sites, such as human immunodeficiency virus (74) and hepatitis B virus (75). …”

“…In this context, over the last few years, intranasal route has emerged as a promising approach for brain delivery of drugs. The delivery from the nose to the CNS may occur via olfactory neuroepithelium and may involve paracellular, transcellular and/or neuronal transport (4, 75,79). Although the olfactory pathway presents potential to bypass BBB, P-gp appears to be also functional on this area (8, 76, 80-82).…”

Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases

“…Owing to the mucoadhesive property of chitosan, the N-trimethylchloride derivative of chitosan was used to demonstrate enhanced immunogenicity and protective efficiency through increased absorption of proteins at the mucosal surfaces by opening tight junctions [24]. In few studies, chitosan particles have been used in combination with alginate for delivery of HBsAg with CpG adjuvant via the intranasal route, which induced significant antibody responses [63]. Furthermore, chitosan as an adjuvant enhanced protection against Helicobacter pylori through induction of Th2 responses [64].…”

Chitosan-Based Particulate Systems for Non-Invasive Vaccine Delivery

“…Borges et al [84] have developed a nanoparticulate delivery system composed of a chitosan core to which HBsAg was adsorbed and subsequently coated with sodium alginate. A potent adjuvant, CpG ODN 1826, that was shown to induce a Th1-type immune response was also associated with the nanoparticles [74]. A high anti-HBsAg IgG titer (2271 AE 120 mIU/mL), with the majority of antibodies being of Th2 type, was observed with the coated nanoparticles.…”

“…Various TLR ligands including CpG-containing oligonucleotides, which have shown adjuvant activity when administered mucosally, were combined with chitosan. Recombinant hepatitis B surface antigen (HBsAg)-loaded nanoparticles were associated with Class B CpG ODN 1826 (5 0 -TCC ATG ACG TTC CTG ACG TT-3 0 ) [74] . The generation of Th1-biased antigen-specific systemic antibodies was observed only when HBsAgloaded nanoparticles were applied together with Class B CpG ODN.…”