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

Tada R, Hidaka A, Iwase N, Takahashi S, Yamakita Y, Iwata T, Muto S, Sato E, Takayama N, Honjo E, Kiyono H, Kunisawa J, Aramaki Y - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Influence of DOTAP/DC-chol liposome particle size on the mucosal adjuvant effect.BALB/c female mice were immunized intranasally with PBS, and treated with DOTAP/DC-chol liposomes of various particle sizes (0.4 μmol/mouse) alone, OVA (5 μg/mouse) alone, or OVA (5 μg/mouse) plus DOTAP/DC-chol liposomes of various particle sizes (0.4 μmol/mouse) on days 0 and 7. Serum and nasal washes were collected on day 14. The anti-OVA IgG, IgG1, and IgG2a levels in serum and anti-OVA IgA level in nasal washes were detected by ELISA assay. The data are obtained from at least three independent experiments. The box-plot shows the median value with the 25th-75th percentiles and the error bars indicate the 5th-95th percentiles. NS: not significant as assessed by the Kruskal–Wallis with Dunn’s post–hoc test.
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pone.0139785.g004: Influence of DOTAP/DC-chol liposome particle size on the mucosal adjuvant effect.BALB/c female mice were immunized intranasally with PBS, and treated with DOTAP/DC-chol liposomes of various particle sizes (0.4 μmol/mouse) alone, OVA (5 μg/mouse) alone, or OVA (5 μg/mouse) plus DOTAP/DC-chol liposomes of various particle sizes (0.4 μmol/mouse) on days 0 and 7. Serum and nasal washes were collected on day 14. The anti-OVA IgG, IgG1, and IgG2a levels in serum and anti-OVA IgA level in nasal washes were detected by ELISA assay. The data are obtained from at least three independent experiments. The box-plot shows the median value with the 25th-75th percentiles and the error bars indicate the 5th-95th percentiles. NS: not significant as assessed by the Kruskal–Wallis with Dunn’s post–hoc test.

Mentions: Particle size is one of the key factors related to the biological effects of nanoparticles [43–45]. To investigate the influence of DOTAP/DC-chol liposome size on mucosal adjuvant activity, we prepared liposomes of various sizes and evaluated their mucosal adjuvant activity. The results indicated that changes in particle size did not affect DOTAP/DC-chol liposome mucosal adjuvant activity (Fig 4).


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

Tada R, Hidaka A, Iwase N, Takahashi S, Yamakita Y, Iwata T, Muto S, Sato E, Takayama N, Honjo E, Kiyono H, Kunisawa J, Aramaki Y - PLoS ONE (2015)

Influence of DOTAP/DC-chol liposome particle size on the mucosal adjuvant effect.BALB/c female mice were immunized intranasally with PBS, and treated with DOTAP/DC-chol liposomes of various particle sizes (0.4 μmol/mouse) alone, OVA (5 μg/mouse) alone, or OVA (5 μg/mouse) plus DOTAP/DC-chol liposomes of various particle sizes (0.4 μmol/mouse) on days 0 and 7. Serum and nasal washes were collected on day 14. The anti-OVA IgG, IgG1, and IgG2a levels in serum and anti-OVA IgA level in nasal washes were detected by ELISA assay. The data are obtained from at least three independent experiments. The box-plot shows the median value with the 25th-75th percentiles and the error bars indicate the 5th-95th percentiles. NS: not significant as assessed by the Kruskal–Wallis with Dunn’s post–hoc test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4594917&req=5

pone.0139785.g004: Influence of DOTAP/DC-chol liposome particle size on the mucosal adjuvant effect.BALB/c female mice were immunized intranasally with PBS, and treated with DOTAP/DC-chol liposomes of various particle sizes (0.4 μmol/mouse) alone, OVA (5 μg/mouse) alone, or OVA (5 μg/mouse) plus DOTAP/DC-chol liposomes of various particle sizes (0.4 μmol/mouse) on days 0 and 7. Serum and nasal washes were collected on day 14. The anti-OVA IgG, IgG1, and IgG2a levels in serum and anti-OVA IgA level in nasal washes were detected by ELISA assay. The data are obtained from at least three independent experiments. The box-plot shows the median value with the 25th-75th percentiles and the error bars indicate the 5th-95th percentiles. NS: not significant as assessed by the Kruskal–Wallis with Dunn’s post–hoc test.
Mentions: Particle size is one of the key factors related to the biological effects of nanoparticles [43–45]. To investigate the influence of DOTAP/DC-chol liposome size on mucosal adjuvant activity, we prepared liposomes of various sizes and evaluated their mucosal adjuvant activity. The results indicated that changes in particle size did not affect DOTAP/DC-chol liposome mucosal adjuvant activity (Fig 4).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.

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.

No MeSH data available.


Related in: MedlinePlus