Secretory IgA and IgG antibodies-inducing agent

A secretory, inducing agent technology, applied in antiviral agents, antibody medical components, allergic diseases, etc., can solve the problems such as the inability of vaccines to obtain mucosal immune responses and insufficient antibody responses, and achieve the defense against flavivirus infection. Effect

Inactive Publication Date: 2008-11-05
森山雅美
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, currently used subcutaneous vaccines cannot elicit a mucosal immune response, and there is a need to develop more effective vaccines with cross-defense capabilities
In particular, as a method of inducing secretory IgA antibodies in the mucous membranes of the respiratory tract, there is a method of inoculating antigens to the nasal mucous membranes through nasal administration (transnasal administration), but sufficient antibody responses cannot be obtained by inoculating antigens alone, so in order to demonstrate more effective The immune response of the vaccine requires the administration of an adjuvant at the same time as the vaccine

Method used

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  • Secretory IgA and IgG antibodies-inducing agent
  • Secretory IgA and IgG antibodies-inducing agent
  • Secretory IgA and IgG antibodies-inducing agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1 : IgA and IgG production ability of synthetic double-stranded RNA Poly(I:C)

[0046] Synthetic double-stranded RNA Poly(I:C) was used as an adjuvant to confirm the ability of inactivated virus or subunit antigens as inactivated antigens to induce neutralizing antibodies, and then confirm the anti-pathogen effect.

[0047] (Material)

[0048] Mice: BALB / c mice (6 weeks old, female)

[0049] Virus: Hantavirus strain (obtained from National Institute of Infectious Diseases (Tokyo)).

[0050] Vaccine: Hantavirus strain (National Institute of Infectious Diseases); ether-treated inactivated vaccine

[0051] Adjuvant: CTB as positive control * [CTB (cholera toxin subunit B), containing 0.1% CT (cholera toxin)] and poly(I:C)

[0052] (method)

[0053] Five 6-week-old BALB / c mice (Nippon SLC Co., Ltd., Tokyo) were used per group. Inoculate 5 μL solution containing 1 μg hantavirus strain vaccine and 0.1 μg, 1 μg, 3 μg or 10 μg poly(I:C) adjuvant in the nasal c...

Embodiment 2

[0084] Example 2 : Efficacy of a nasal hantavirus vaccine combining inactivated virions and poly(I:C) defensive effect

[0085] (Material)

[0086] Vaccines: ether treated hantavirus HA vaccine; formalin inactivated whole virion NC vaccine

[0087] Mice: BALB / c mice (6 weeks old, female)

[0088] (method)

[0089] 0.1 μg formalin inactivated whole particle NC hantavirus vaccine combined with 0.1 μg poly(I:C) [100-1000bp: Toray] as a vaccine component of nasal hantavirus vaccine against BALB / c mice (6-week-old, female) was administered, and the same vaccine was administered again 3 weeks later.

[0090] After an additional week, the antibody responses in nasal washes and serum of the mice were measured as indicators of mucosal and systemic protective immunity, respectively.

[0091] (result)

[0092] The results are shown in Table 4.

[0093] [Table 4]

[0094]

[0095] From the results in the table, it is clear that the combination of inactivated whole virions ...

Embodiment 3

[0099] Example 3 : Confirm the molecular size of poly(I:C)

[0100] (Material)

[0101] Virus: Hantavirus

[0102] Poly(I:C):

[0103] Size (L): 1~300bp (Fluka)

[0104] Size (M): 100 ~ 1000bp (Toray)

[0105] Size (H): >3.3×10 6 bp (Fluka)

[0106] Poly(A:U)

[0107] Mice: BALB / c mice (6 weeks old, female)

[0108] (method)

[0109] BALB / c mice (6 weeks old, female) were intranasally administered 0.4 μg of the lysate vaccine of hantavirus and 0.1 μg of poly(I:C) of various sizes, and the same vaccine was administered again 3 weeks later.

[0110] After another week, the antibody responses against HA and NA in nasal washes and serum of the mice were measured as indicators of mucosal and systemic protective immunity, respectively.

[0111] (result)

[0112] The results are shown in Table 7.

[0113] [table 5]

[0114]

[0115]

[0116] From the results shown in the table, it was found that the mucosal response was lower in the experimental group using poly...

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PUM

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Abstract

It is intended to provide a nasal vaccine capable of inducing the production of secretory IgA and IgG antibodies which are specific to a Flavivirus such as a Hantavirus. It is also intended to provide a method of preventing infection with a Flavivirus by inducing the secretory IgA and IgG antibodies as described above. Namely, a nasal vaccine whereby favorable secretion of IgA antibody on the nasal mucosa and an IgG antibody response in the serum can be established, characterized in that a vaccine comprising an inactivated antigen originating in a Flavivirus and Poly(I:C) or a ceramic-processed surf clam powder employed as an adjuvant is nasally administered; and a method of inducing IgA and IgG antibodies specific to a Flavivirus characterized by comprising administering an inactivated antigen of a Flavivirus and Poly(I:C) or a ceramic-processed surf clam powder employed as an adjuvant to the mucosa of an respiratory organ.

Description

technical field [0001] The present invention relates to a method for inducing production of flavivirus-specific secretory IgA and IgG antibodies by simultaneous nasal administration of a vaccine which is an inactivated antigen of flavivirus and an adjuvant. The present invention also relates to a method of protecting against flavivirus infection by inducing the production of such secretory IgA and IgG antibodies by nasal administration and secretory IgA and IgG antibody inducers. Background technique [0002] Recently, infectious diseases caused by flaviviruses have received attention. Infectious diseases caused by West Nile virus, dengue virus, Japanese encephalitis virus, yellow fever virus, tick-borne encephalitis virus, and hepatitis C virus in the Flaviviridae family have become major global problems. [0003] In addition, recently, infectious diseases caused by hantavirus, one of the flaviviruses, have also gradually become a major problem. However, attention to infe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/12A61K39/39A61P11/00A61P31/12
CPCA61K2039/541A61K2039/543C12N2760/12134A61K39/12A61K2039/55561A61K2039/55588A61K2039/5252C12N2770/24034A61K39/39A61P11/00A61P31/12A61P31/14A61P37/02Y02A50/30
Inventor 森山雅美长谷川秀树佐多彻太郎仓田毅田中利明
Owner 森山雅美
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