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

Rui Tada,Jun Kunisawa,Yukihiko Aramaki,Tomoko Iwata,Hiroshi Kiyono,Noriko Takayama,Akira Hidaka,Naoko Iwase,Shoko Muto,Emi Sato,Saeko Takahashi,Emi Honjo,Yuki Yamakita,Prosper N Boyaka

doi:10.1371/journal.pone.0139785

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.

Highlights

Infectious diseases are still one of the most important risk factors for human disease and the second leading cause of death [1, 2]
We examined the stability of cationic liposomes composed of DOTAP and dendritic cells (DCs)-cholesterol (DOTAP/DC-chol liposomes) as well as DOTAP and cholesterol (DOTAP/chol liposomes)
The results demonstrated that the DOTAP/DC-chol liposome was exceptionally stable compared to the DOTAP/chol liposome, as seen in S1 Fig

Summary

Introduction

Infectious diseases are still one of the most important risk factors for human disease and the second leading cause of death [1, 2]. Mucosal vaccines are a promising strategy for preventing infectious diseases since mucosal surfaces are a major route of entry for most pathogens and mucosal adjuvants are known to induce potent systemic and mucosal antigen-specific immune responses [4,5,6]. Recent vaccine research has focused on the production of antibodies at mucosal sites to prevent pathogen entry into the host [7,8,9] Such approaches have proven impractical for clinical use due to safety and efficacy concerns. The majority of approved vaccines worldwide are administered by subcutaneous or intramuscular injection and induce systemic immune responses but not mucosal immune responses To solve this problem, the development of mucosal vaccines is essential. The development of safe and effective mucosal adjuvants is key to preventing infectious diseases by enabling the use of mucosal vaccines in the clinic

Methods

Results

Discussion

Conclusion