Peptide immunogens of IL-31 and formulations thereof for the treatment and/or prevention of atopic dermatitis
A technology of IL-31, peptide immunogen, applied in the field of pharmaceutical compositions for the treatment and/or prevention of atopic dermatitis, can solve the problems of increasing the susceptibility of atopic dermatitis and the like
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[0204] (1) An IL-31 peptide immunogen construct, which can be represented by the following formula:
[0205] (Th) m -(A) n -(IL-31 Fragment)-X
[0206] or
[0207] (IL-31 Fragment)-(A) n -(Th) m -X
[0208] in
[0209] Th is a heterologous T helper cell epitope;
[0210] A is a heterologous spacer;
[0211] (IL-31 fragment) is a B cell epitope having about 15 to about 75 amino acid residues from SEQ ID NO: 1 or SEQ ID NO: 2;
[0212] X is α-COOH or α-CONH of amino acid 2 ;
[0213] m is 1 to about 4; and
[0214] n is 0 to about 10.
[0215] (2) The IL-31 peptide immunogen construct according to (1), wherein the IL-31 fragment is selected from the group consisting of SEQ ID NO: I-13 and 93 to 98.
[0216] (3) The IL-31 peptide immunogen construct according to any one of (1) or (2), wherein the T helper epitope is selected from the group consisting of SEQ ID NO: 14-42.
[0217] (4) The IL-31 peptide immunogen construct according to (1), wherein the peptide immunog...
Embodiment 1
[0239] Example 1. Synthesis of IL-31-related peptides and preparation of dosage forms thereof
[0240] a. IL-31 fragment
[0241] Methods to synthesize specifically designed IL-31 fragments included in the IL-31 peptide immunogen construct development program are described. The peptides synthesized in small scale quantities are used in serological assays, laboratory tests and field trials, which can be used to analyze pharmaceutical compositions. In order to screen and select optimal peptide constructs for use in potent IL-31 peptide immunogen constructs, a large number of IL-31-associated antigenic peptides comprising sequences with a length of about 15 to about 75 amino acids were designed (Table 1) .
[0242] Using IL-31 (SEQ ID NO: 1) from full length canine ( Figure 1A ) and amino acid sequences of human IL-31 (SEQ ID No: 2) proteins. IL-31 fragments (SEQ ID NO: 3-13 and 93 to 98) used for epitope identification in various serological assays are identified in Table 1...
Embodiment 2
[0246] Example 2. Immunization of guinea pigs with IL-31 peptide immunogen constructs for immunogenicity assessment
[0247] a.Animals
[0248] Guinea pigs weighing 300-350 g were used for immunization to assess the immunogenicity of representative canine IL-31 peptide immunogen constructs (SEQ ID NOs: 43, 47, 51, 55 and 59). As shown in Table 4, 15 guinea pigs were grouped with 3 animals per group and primed with 400 μg of peptide followed by 4 doses of 100 μg at 3, 6, 9 and 12 weeks post prime (wpi) booster immunity. Blood samples were collected at 0, 3, 6, 9, 12 and 15 wpi to determine the titers of anti-IL-31 antibodies and other functional properties of the antibodies present in the corresponding immune sera.
[0249] b. dosage form
[0250] The preparation for immunization contains the following substances:
[0251] 1.400 μg of IL-31 peptide immunogen construct
[0252] 2. CpG with a peptide:CpG ratio of 0.7:1
[0253] 3.0.2% TWEEN80
[0254] c. Determination of s...
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