Human m2e peptide immunogens

Abstract

The present invention provides novel peptide immunogens comprising influenza virus matrix 2 protein epitopes and related compositions and methods. The present invention relates to a composition comprising a peptide immunogen useful for the prevention and treatment of an influenza virus-mediated disease. The invention also relates to vaccines, immunogenic products and immunogenic compositions containing the peptide immunogens.

What is claimed: 
     
         1 . A peptide immunogen comprising a sequence of:
 [Xaa 0 ] m -Xaa 1 -Xaa 2 -Xaa 3 -Xaa 4 -Xaa 5 -[Xaa 6 ] p -[Xaa 7 ] q -[Xaa 8 -[Xaa 0 ] m -Xaa 1 -Xaa 2 -Xaa 3 -Xaa 4 -Xaa 5 -[Xaa 6 ] p -[Xaa 7 ] q ] n      wherein, m, p and q are independently 0 or 1,   n is any number between 0 and 4,   Xaa 0 , Xaa 6 , Xaa 7  and Xaa 8  is independently any amino acid,   Xaa 1 -Xaa 2 -Xaa 3 -Xaa 4 -Xaa 5  is S-L-L-T-E, or a peptide having a single substitution to the sequence S-L-L-T-E, wherein the substitution is selected from the group consisting of:   (i):
 Xaa 1  is C or T; 
 Xaa 2  is A, C, F or K, 
 Xaa 3  is A, C, E, F, I, K, M, Q, S, T or V, and 
 Xaa 5  is D or C; and 
   (ii):
 Xaa 1  is A, C, D, L, T or V, 
 Xaa 2  is A, C, F, H, I, K, M, N, Q, R, T, W, or Y, 
 Xaa 3  is any amino acid, 
 Xaa 4  is M, N, Q, S, or W, and 
 Xaa 5  is A, D, F, H, I, K, M, N, Q, S, W, Y, or C. 
   
     
     
         2 . The peptide immunogen of  claim 1 , wherein Xaa 0  is C. 
     
     
         3 . The peptide immunogen of  claim 1 , wherein Xaa 6  is V or C. 
     
     
         4 . The peptide immunogen of  claim 1 , wherein Xaa 7  is E. 
     
     
         5 . The peptide immunogen of  claim 1 , wherein Xaa 8  is G or A. 
     
     
         6 . The peptide immunogen of  claim 1 , wherein said peptide is non-linear. 
     
     
         7 . The peptide immunogen of  claim 6 , wherein said peptide is cyclic. 
     
     
         8 . The peptide immunogen of  claim 6 , wherein said peptide is cyclic and n is any number between 1 and 4. 
     
     
         9 . The peptide immunogen of  claim 1 , wherein said peptide binds specifically to HuMe2 antibodies 8I10 or 23K12. 
     
     
         10 . The peptide immunogen of  claim 1 , wherein said peptide comprises D-amino acids. 
     
     
         11 . The peptide immunogen of  claim 1 , wherein said peptide is a linear or cyclized peptide having a sequence selected from the group consisting of SLLTEVGSLLTEV (SEQ ID NO: 320); CSLLTEVGSLLTEV (SEQ ID NO: 283); and CSLLTECGSLLTCV (SEQ ID NO: 463). 
     
     
         12 . The peptide immunogen of  claim 1 , wherein said peptide does not bind the antibody Z3G1. 
     
     
         13 . The peptide immunogen of  claim 1 , wherein said peptide is conjugated to a carrier. 
     
     
         14 . The peptide immunogen of  claim 13 , wherein the carrier is human serum albumin, keyhole limpet hemocyanin (KLH), immunoglobulin molecules, thyroglobulin, ovalbumin, influenza hemagglutinin, PAN-DR binding peptide (PADRE polypeptide), malaria circumsporozite (CS) protein, hepatitis B surface antigen (HBSAg 19-28 , Heat Shock Protein (HSP) 65,  Bacillus  Calmette-Guerin (BCG), cholera toxin, cholera toxin mutants with reduced toxicity, diphtheria toxin, CRM 197  protein that is cross-reactive with diphtheria toxin, recombinant Streptococcal C5a peptidase,  Streptococcus pyogenes  ORF1224,  Streptococcus pyogenes  ORF1664,  Streptococcus pyogenes  ORF 2452,  Chlamydia pneumoniae  ORF T367,  Chlamydia pneumoniae  ORF T858, Tetanus toxoid, HIV gp120 T1, microbial surface components recognizing adhesive matrix molecules (MSCRAMMS), growth factor/hormone, cytokine or chemokine. 
     
     
         15 . A vaccine composition comprising the peptide immunogen of  claim 1 . 
     
     
         16 . The composition of  claim 15 , further comprising an adjuvant selected from the group consisting of mineral salts, GM-CSF, 529 SE, IL-12, aluminum phosphate, aluminum hydroxide,  Mycobacterium tuberculosis, Bordetella pertussis , bacterial lipopolysaccharides, aminoalkyl glucosane phosphate compounds, MPL™ (3-O-deacylated monophosphoryl lipid A), a polypeptide, Quil A, STIMULON™ QS-21, a pertussis toxin (PT), an  E. coli  heat-labile toxin (LT), IL-1alpha, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, interferon-alpha, interferon-β, interferon-gamma, G-CSF, TNF-alpha and TNF-β and Freund's complete adjuvant (FCA). 
     
     
         17 . An immunogenic composition, comprising the peptide immunogen of  claim 1 , together with one or more pharmaceutically acceptable excipients, diluents, and/or adjuvants. 
     
     
         18 . The immunogenic composition of  claim 17 , wherein the pharmaceutically acceptable adjuvant and/or carrier is selected from the group consisting of alum, liposyn, saponin, squalene, L121, emulsigen monophosphyryl lipid A (MPL), polysorbate 80, QS21, Montanide ISA51, ISA35, ISA206 and ISA 720. 
     
     
         19 . A method of preventing or treating an influenza virus mediated disease by administrating to a mammal a peptide immunogen according to  claim 1 . 
     
     
         20 . A kit comprising the peptide immunogen according to  claim 1 .