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Nucleic acids for treatment of peanut allergies

A peanut allergen, nucleic acid molecule technology, applied in the fields of molecular biology and medicine, can solve the problem of varying degrees

Inactive Publication Date: 2017-02-22
IMMUNOMIC THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Immunotherapy, the administration of increasing doses of an allergen to induce tolerance, is the standard treatment for allergic disease but has not been approved for the treatment of peanut allergy due to frequent anaphylaxis (Nelson et al, (1997) J. Allergy Clin. Immunol 99;6:744-751; Oppenheimer et al. (1992) J. Allergy Clin. Immunol 90:256-262)
Furthermore, the use of immunotherapy is limited by the length of treatment, which requires up to 36 months of weekly or biweekly injections, and the degree of success and compliance varies (Bousquet et al., (1998) J. Allergy Clin. Immunol 102 :558-562; Rank and Li (2007) Mayo Clin.Proc.82(9):1119-1123; Ciprandi et al., (2007) Allergy Asthma Proc.28:40-43)

Method used

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  • Nucleic acids for treatment of peanut allergies
  • Nucleic acids for treatment of peanut allergies
  • Nucleic acids for treatment of peanut allergies

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0125] Example 1: General Materials and Methods

[0126] Genetic sequences encoding the peanut allergens Ara H1, Ara H2 and Ara H3 were prepared as native sequences (control plasmid) and as chimeras with human LAMP-1 (experimental plasmid), wherein each sequence was inserted in the LAMP Between the luminal domain and the transmembrane domain. Previous studies have shown that antigenic sequences must be optimized for human use, thus removing all non-essential or deleterious elements (cryptic splice sites, secondary RNA / DNA structures, secondary ORFs) in order to maximize RNA stability sex and protein expression. AraH1-LAMP comprises SEQ ID NO:15. AraH2-LAMP comprises SEQ ID NO:12. The final optimized sequence was chemically synthesized and inserted into the LAMP open reading frame (ORF) of the antibiotic-free pDNA-VACC-ultra vector (Nature Pharmaceuticals, Lincoln, NE). Chimeric protein expression for each plasmid was determined by transfection of NIH3T3 cells followed by...

Embodiment 2

[0135] Example 2: ARA-LAMP Prevention Study

[0136] The prophylactic effectiveness of DNA constructs comprising the peanut allergens Ara H1, Ara H2 and / or Ara H3 was tested in a mouse model. The polyvalent LAMP plasmids encoding the peanut allergens Ara H1, Ara H2 and Ara H3 (AraH1 / H2 / H3-LAMP generated according to Example 1) were mixed with a three-plasmid mixture each encoding a single peanut allergen (according to Example 1). 1 prepared AraH1-LAMP, AraH2-LAMP and ARAH3del-LAMP) for comparison. BALB / c mice were immunized once a week for three weeks with 50 μg of a single multivalent peanut plasmid or 50 μg of each individual plasmid by intradermal (ID) or intramuscular (IM) injection. IgG1 and IgG2a antibody titers were determined by ELISA 5 weeks after the last immunization. Multivalent plasmids were found to be allergenic, but the magnitude of the antibody response was lower than a single allergen delivery in multiple plasmids ( Figure 5 and 6 ). Without wishing t...

Embodiment 3

[0141] Example 3: ARA-LAMP therapeutic study

[0142] Experiments were also performed to determine the ability of the DNA vaccines of the present disclosure to provide therapeutic treatment. A representative scheme is shown in the Figure 17 wherein the mice were first sensitized with peanut butter and cholera toxin, and then the ARA-LAMP-vax triple plasmid (AraH1-LAMP, AraH2-LAMP and Ara-H3del-LAMP prepared according to Example 1) composition treat. Figure 18 Shown are IgE antibody levels in the weeks preceding vaccine treatment with the three-plasmid mixture ARA-LAMP-vax, each encoding a single peanut allergen.

[0143] When multivalent DNA vaccines were used, IgE antibody levels decreased at week 15 after vaccine treatment ( Figure 19 ). Anaphylaxis challenge results (symptom score, Figure 20 , Figure A; body temperature, Figure 20 , Figure B; Figure 21 ) showed that administration of the ARA-LAMP-vax three-plasmid composition resulted in less severe symptoms ...

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Abstract

Provided herein are DNA vaccines for the treatment of peanut allergies. The vaccines comprise the coding sequence for one or more peanut allergenic epitopes fused in-frame with the luminal domain of the lysosomal associated membrane protein (LAMP) and the targeting sequence of LAMP. The vaccines can be multivalent molecules and / or can be provided as part of a multivalent vaccine comprising two or more DNA constructs.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Application No. 62 / 015,981 filed June 23, 2014, which is hereby incorporated by reference in its entirety. technical field [0003] The subject matter of the present disclosure relates to the fields of molecular biology and medicine. More specifically, the subject matter of the present disclosure relates to nucleic acids for use as DNA vaccines and methods of using them to treat subjects suffering from or susceptible to peanut allergy. Background technique [0004] Allergic reactions occur when the immune system responds to harmless foreign substances called allergens. Food allergy is an important public health problem due to the high risk of anaphylaxis, a potentially fatal systemic shock (Sampson et al., (1992) N.Engl.J.Med.327:380-384; Bock et al., (2001 ) J. Allergy Clin. Immunol. 107:191-193). Young children have a higher risk of developing food allergies than the gener...

Claims

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Application Information

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IPC IPC(8): C12N15/62C07K19/00C12N15/85C12N5/10A61K39/35A61P37/08
CPCA61K39/35A61K2039/53A61K2039/577A61K2039/70C07K14/415C07K2319/02C07K2319/03C07K2319/06C07K2319/35A61K2039/54A61K2039/57A61P37/00A61P37/08C07K5/1016C07K14/47C07K14/70596
Inventor 威廉·赫尔特瑞·海兰
Owner IMMUNOMIC THERAPEUTICS
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