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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

Induction of OVA-specific serum IgG and nasal tissue IgA responses in BALB/c mice immunized intranasally with OVA and cationic liposomes.BALB/c female mice were immunized intranasally with PBS, OVA (5 μg/mouse) alone, or OVA (5 μg/mouse) plus various cationic liposomes (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 as described in the “Materials and Methods” section. The data were 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. Significance was assessed using the Kruskal–Wallis with Dunn’s post–hoc test: *p < 0.05, **p < 0.01, NS: not significant.
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pone.0139785.g001: Induction of OVA-specific serum IgG and nasal tissue IgA responses in BALB/c mice immunized intranasally with OVA and cationic liposomes.BALB/c female mice were immunized intranasally with PBS, OVA (5 μg/mouse) alone, or OVA (5 μg/mouse) plus various cationic liposomes (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 as described in the “Materials and Methods” section. The data were 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. Significance was assessed using the Kruskal–Wallis with Dunn’s post–hoc test: *p < 0.05, **p < 0.01, NS: not significant.

Mentions: We examined whether intranasal administration of the cationic liposomes acts as a mucosal adjuvant in BALB/c female mice. Mice were immunized intranasally twice weekly with OVA alone or combined with the cationic liposomes (DOTAP/DC-chol or DOTAP/chol liposomes). Intranasal vaccination with OVA and the cationic liposomes induced expression of OVA-specific IgA in nasal tissue and IgG in serum. Intranasal immunization with PBS or OVA alone did not induce OVA-specific immunoglobulin expression in nasal tissue or serum in this experiment (Fig 1).


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)

Induction of OVA-specific serum IgG and nasal tissue IgA responses in BALB/c mice immunized intranasally with OVA and cationic liposomes.BALB/c female mice were immunized intranasally with PBS, OVA (5 μg/mouse) alone, or OVA (5 μg/mouse) plus various cationic liposomes (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 as described in the “Materials and Methods” section. The data were 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. Significance was assessed using the Kruskal–Wallis with Dunn’s post–hoc test: *p < 0.05, **p < 0.01, NS: not significant.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139785.g001: Induction of OVA-specific serum IgG and nasal tissue IgA responses in BALB/c mice immunized intranasally with OVA and cationic liposomes.BALB/c female mice were immunized intranasally with PBS, OVA (5 μg/mouse) alone, or OVA (5 μg/mouse) plus various cationic liposomes (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 as described in the “Materials and Methods” section. The data were 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. Significance was assessed using the Kruskal–Wallis with Dunn’s post–hoc test: *p < 0.05, **p < 0.01, NS: not significant.
Mentions: We examined whether intranasal administration of the cationic liposomes acts as a mucosal adjuvant in BALB/c female mice. Mice were immunized intranasally twice weekly with OVA alone or combined with the cationic liposomes (DOTAP/DC-chol or DOTAP/chol liposomes). Intranasal vaccination with OVA and the cationic liposomes induced expression of OVA-specific IgA in nasal tissue and IgG in serum. Intranasal immunization with PBS or OVA alone did not induce OVA-specific immunoglobulin expression in nasal tissue or serum in this experiment (Fig 1).

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