The Development of Surface-Modified Liposomes as an Intranasal Delivery System for Group A Streptococcus Vaccines

Intranasal vaccine administration can overcome the disadvantages of injectable vaccines and present greater efficiency for mass immunization. However, the development of intranasal vaccines is challenged by poor mucosal immunogenicity of antigens and the limited availability of mucosal adjuvants. Here, we examined a number of self-adjuvanting liposomal systems for intranasal delivery of lipopeptide vaccine against group A Streptococcus (GAS). Among them, two liposome formulations bearing lipidated cell-penetrating peptide KALA and a new lipidated chitosan derivative (oleoyl-quaternized chitosan, OTMC) stimulated high systemic antibody titers in outbred mice. The antibodies were fully functional and were able to kill GAS bacteria. Importantly, OTMC was far more effective at stimulating antibody production than the classical immune-stimulating trimethyl chitosan formulation. In a simple physical mixture, OTMC also enhanced the immune responses of the tested vaccine, without the need for a liposome delivery system. The adjuvanting capacity of OTMC was further confirmed by its ability to stimulate cytokine production by dendritic cells. Thus, we discovered a new immune stimulant with promising properties for mucosal vaccine development.

Automated summary

Intranasal vaccine administration has advantages in mass immunization. A new liposomal system using lipidated chitosan derivative (OTMC) showed promising results in stimulating high systemic antibody titers against group A Streptococcus (GAS) in mice. OTMC was more effective than the traditional trimethyl chitosan formulation and could enhance the immune responses of the vaccine without the need for a liposome delivery system. Importantly, OTMC also stimulated cytokine production by dendritic cells, indicating its potential for mucosal vaccine development.