Intranasal Immunization with DOTAP Cationic Liposomes Combined with DC-Cholesterol Induces Potent Antigen-Specific Mucosal and Systemic Immune Responses in Mice

Abstract

Despite the progress made by modern medicine, infectious diseases remain one of the most important threats to human health. Vaccination against pathogens is one of the primary methods used to prevent and treat infectious diseases that cause illness and death. Vaccines administered by the mucosal route are potentially a promising strategy to combat infectious diseases since mucosal surfaces are a major route of entry for most pathogens. However, this route of vaccination is not widely used in the clinic due to the lack of a safe and effective mucosal adjuvant. Therefore, the development of safe and effective mucosal adjuvants is key to preventing infectious diseases by enabling the use of mucosal vaccines in the clinic. In this study, we show that intranasal administration of a cationic liposome composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] (DC-chol) (DOTAP/DC-chol liposome) has a potent mucosal adjuvant effect in mice. Intranasal vaccination with ovalbumin (OVA) in combination with DOTAP/DC-chol liposomes induced the production of OVA-specific IgA in nasal tissues and increased serum IgG1 levels, suggesting that the cationic DOTAP/DC-chol liposome leads to the induction of a Th2 immune response. Additionally, nasal-associated lymphoid tissue and splenocytes from mice treated with OVA plus DOTAP/DC-chol liposome showed high levels of IL–4 expression. DOTAP/DC-chol liposomes also enhanced OVA uptake by CD11c+ dendritic cells in nasal-associated lymphoid tissue. These data demonstrate that DOTAP/DC-chol liposomes elicit immune responses via an antigen-specific Th2 reaction. These results suggest that cationic liposomes merit further development as a mucosal adjuvant for vaccination against infectious diseases.

Mixed cationic liposomes for brain delivery of drugs by the intranasal route: The acetylcholinesterase reactivator 2-PAM as encapsulated drug model

“…Cationic liposomes deserve attention and further development since the ability of nanoparticles to penetrate the nasal mucus is obviously dependent not only on the size, but also, primarily, on the surface charge of particles [24]. In addition, the positive charge of liposomes plays an important role in the in vitro processes of interaction with cells epithelium [25] and as a mucosal adjuvant [8,26]. We applied the cationic liposome intranasal drug delivery approach in the treatment of organophosphorus poisoning.…”

Liposome-entrapped GABA modulates the expression of nNOS in NG108-15 cells

“…Utilizing this mode of carrier mechanism, various studies have used administration of intranasal liposomes in many diseases, such as Alzheimer (Corace et al, 2014; Zheng et al, 2015), Parkinson (Migliore et al, 2014) and tuberculosis (Leemans et al, 2001). Also, intranasal liposomes have also been used in the preparation of vaccines against bacterial and fungal infectious diseases such as pneumonia, influenza, and tuberculosis (Khatri et al, 2008; Romero and Morilla, 2011; Tada et al, 2015; Tiwari et al, 2011). …”

Mechanisms of Enhanced Antigen Delivery to Murine Dendritic Cells by the Cationic Liposomes

“…Liposomes were prepared as described earlier [19]. Briefly, 10 μmol of total lipids (DOTAP:DC-chol at 1:1 mol ratios) were evaporated to dryness in a glass tube and desiccated for at least 1 h in vacuo.…”

“…The detailed molecular mechanism(s) behind the adjuvant effects of the cationic liposomes are not completely elucidated. We have previously reported that cationic liposome promotes antigen uptake into the DCs located at nasal-associated lymphoid tissues (NALTs) in vivo [19] [20]. Although, how the cationic liposome increases antigen uptake by DCs remains unclear till date.…”