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Problems solved by technology
Injectable vaccines have the problem of inducing an immune response (IgG antibody production) in the blood (systemic) without inducing an immune response (IgA antibody production) in the mucous membranes, although it can prevent the pathogens caused by infection. proliferates, but has difficulty defending itself from infection by pathogens due to the mucosal route
Thus, from the example of the vaccine using lipopolysaccharide (LPS) derived from Pantoea agglomerans (Pantoea agglomerans) described in this patent document 3, the oral mucosa, eye mucosa, ear mucosa, genital mucosa, throat mucosa, respiratory tract mucosa , bronchial mucosa, pulmonary mucosa, gastric mucosa, intestinal mucosa, or rectal mucosa, it is unclear whether lipopolysaccharide (LPS) derived from Pantoea agglomerans (Pantoea agglomerans) exerts an effect
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Examples
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Embodiment 1
[0117] 2.25 μL (445 μg / mL) of a solution containing influenza vaccine antigen (B / Wisconsin / 1 / 2010, manufactured by Osaka University Institute of Microbial Diseases) and lipopolysaccharide derived from Pantoea agglomerans (NACALAITESQUE, INC. Phosphate buffer (manufactured by NACALAITESQUE, INC.) was added to 5 μL (2 mg / mL) of the solution to prepare 300 μL of a mucosal vaccine composition.
[0118] Six mice (8-week-old female BALB / C mice, Japan SLC, Inc.) were anesthetized, and 30 μL of the prepared vaccine composition was sublingually administered to each mouse. One week after the administration, the mice were anesthetized again, and 30 μL of the prepared vaccine composition was sublingually administered to each mouse. After the second administration and one week later, the serum and nasal cavity washing fluid of the mice were collected, and for the titer of influenza HA (type B)-specific IgG in the serum and the specific IgA of influenza HA (type B) in the nasal cavity washing...
Embodiment 2
[0124] Add 1.25 μL (801 μg / mL) of a solution containing influenza vaccine antigen (A / California / 07 / 2009 (H1N1), manufactured by Osaka University Institute of Microbial Diseases) and lipopolysaccharide (NACALAITESQUE , INC.) was added to 5 μL (2 mg / mL) of a phosphate buffer solution (NACALAITESQUE, INC.) to prepare a 300 μL mucosal vaccine composition.
[0125] Six mice (8-week-old female BALB / C mice, Japan SLC, Inc.) were anesthetized, and 30 μL of the prepared mucosal vaccine composition was sublingually administered to each mouse. One week after the administration, the mice were anesthetized again, and 30 μL of the prepared mucosal vaccine composition was sublingually administered to each mouse. After the second administration and one week later, the serum and nasal cavity washing fluid of the mice were collected, and the influenza HA (H1N1) specific IgG titer in the serum and the influenza HA (H1N1) specific IgA titer in the nasal cavity washing fluid were collected. The d...
reference example 1
[0131] A sample containing the same antigen and immunostimulant as in the sample administered in Example 1, and the same (antigen / immunostimulant) as in Example 1 was produced, and its safety was evaluated. That is, 225 μL (445 μg / mL) of a solution containing influenza vaccine antigen (B / Wisconsin / 1 / 2010, manufactured by Osaka University Institute of Microbial Diseases) and lipopolysaccharide derived from Pantoea agglomerans (NACALAITESQUE, INC .) solution (2 mg / mL) was added to 500 μL (2 mg / mL) of phosphate buffer (NACALAITESQUE, INC.) to prepare 1000 μL of vaccine composition.
[0132] Eight mice (8-week-old female BALB / C mice, Japan SLC, Inc.) were anesthetized, and 100 μL of the prepared vaccine composition was subcutaneously administered to each mouse. The mice were followed up to 72 hours after the administration, and the survival rate was observed.
[0133] (Refer to Comparative Examples 1 and 2)
[0134] Instead of the lipopolysaccharide derived from Pantoea agglomer...
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Abstract
The purpose of the present invention is to provide a mucosal vaccine composition that is effective and safe as a prophylactic or therapeutic drug for infections and cancer, which effectively induces a systemic immune response and mucosal immune response, and which can be administered to the oral mucosa, ocular mucosa, ear mucosa, genital mucosa, pharyngeal mucosa, respiratory mucosa, bronchial mucosa, pulmonary mucosa, gastric mucosa, intestinal mucosa, or rectal mucosa. The present invention is a mucosal vaccine composition administered to at least one mucous membrane of a person or animal, said mucous membrane being selected from the group consisting of oral mucosa, ocular mucosa, ear mucosa, genital mucosa, pharyngeal mucosa, respiratory mucosa, bronchial mucosa, pulmonary mucosa, gastric mucosa, intestinal mucosa, and rectal mucosa. The mucosal vaccine composition is characterized by including at least one type of antigen, and, as an immunostimulant, a lipopolysaccharide or a salt thereof derived from at least one gram-negative bacterium selected from the group consisting of Serratia, Leclercia, Rahnella, Acidicaldus, Acidiphilium, Acidisphaera, Acidocella, Acidomonas, Asaia, Belnapia, Craurococcus, Gluconacetobacter, Gluconobacter, Kozakia, Leahibacter, Muricoccus, Neoasaia, Oleomonas, Paracraurococcus, Rhodopila, Roseococcus, Rubritepida, Saccharibacter, Stella, Swaminathania, Teichococcus, Zavarzinia, Pseudomonas, Achromobacter, Bacillus, Methanoculleus, Methanosarcina, Clostridium, Micrococcus, Flavobacterium, Pantoea, Acetobacter, Zymomonas, Xanthomonas, and Enterobacter.
Description
technical field [0001] The present invention relates to an agent useful as a preventive or therapeutic agent for infectious diseases and cancer, and capable of treating oral mucosa, ocular mucosa, ear mucosa, genital mucosa, throat mucosa, respiratory tract mucosa, bronchial mucosa, lung mucosa, gastric mucosa, intestinal mucosa or Mucosal vaccine compositions for rectal mucosal administration. In particular, the present invention relates to a mucosal vaccine composition capable of safely and effectively inducing a systemic immune response and a mucosal immune response by administering a specific lipopolysaccharide as an adjuvant to the mucosal surface together with an antigen. Background technique [0002] As the dosage form of vaccine preparations, most of the commercialized preparations are now injections. Injectable vaccines have the problem of inducing an immune response (IgG antibody production) in the blood (systemic) without inducing an immune response (IgA antibody...
Claims
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