Abstract
Peptide subunit vaccines hold great potential compared to traditional vaccines. However, peptides alone are poorly immunogenic. Therefore, it is of great importance that a vaccine delivery platform and/or adjuvant that enhances the immunogenicity of peptide antigens is developed. Here, we report the development of two different systems for the delivery of lipopeptide subunit vaccine (LCP-1) against group A streptococcus: polymer-coated liposomes and polyelectrolyte complexes (PECs). First, LCP-1-loaded and alginate/trimethyl chitosan (TMC)-coated liposomes (Lip-1) and LCP-1/alginate/TMC PECs (PEC-1) were examined for their ability to trigger required immune responses in outbred Swiss mice; PEC-1 induced stronger humoral immune responses than Lip-1. To further assess the adjuvanting effect of anionic polymers in PECs, a series of PECs (PEC-1 to PEC-5) were prepared by mixing LCP-1 with different anionic polymers, namely alginate, chondroitin sulfate, dextran, hyaluronic acid, and heparin, then coated with TMC. All produced PECs had similar particle sizes (around 200 nm) and surface charges (around + 30 mV). Notably, PEC-5, which contained heparin, induced higher antigen-specific systemic IgG and mucosal IgA titers than all other PECs. PEC systems, especially when containing heparin and TMC, could function as a promising platform for peptide-based subunit vaccine delivery for intranasal administration.
Highlights
Vaccination is perceived as one of the most effective approaches for the prevention and containment of infectious diseases
Chitosan, sodium alginate, dextran sodium, chondroitin sulfate, heparin sodium, cholera toxin B subunit (CTB), horseradish peroxidase (HRP)-conjugated goat anti-mouse IgG and IgA, high performance liquid chromatography (HPLC) solvent, and all other reagents were purchased from Sigma-Aldrich (Sydney, Australia)
When positively charged liposomes were coated with 30 μg of negatively charged alginate, both the particle size and polydispersity index (PDI) increased while the surface charge reverted to −21.0 mV
Summary
Vaccination is perceived as one of the most effective approaches for the prevention and containment of infectious diseases. Vaccines are developed to trigger immunity against specific pathogens once administered into the body. Traditional vaccines are normally produced from attenuated or inactivated forms of whole pathogenic microorganisms. The use of whole pathogens is associated with potential drawbacks, such as the risk of infection, auto-immune and strong allergic responses, low yield of production, and low storage stability [1]. In order to avoid these disadvantages, subunit vaccines, such as peptide vaccines, have emerged [2,3]. Peptide-based subunit vaccines contain the most essential fragments of a pathogen needed to stimulate desired immune responses. Without the assistance of an adjuvant, peptides cannot stimulate long-lasting immune responses [4]
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