Multiple antigen presenting system (maps)-based staphylococcus aureus vaccine, immunogenic composition, and uses thereof

Abstract

The present embodiments provide for an S. aureus (SA) Multiple Antigen Presenting System (MAPS) immunogenic composition comprising an immunogenic polysaccharide which induces an immune response, where at least one S. aureus (SA) peptide or polypeptide antigen is associated to the immunogenic polysaccharide by complementary affinity molecules. In some embodiments, the immunogenic polysaccharide can be an antigenic capsular polysaccharide of a Type 5 or Type 8 from S. aureus, or alternatively, a different immunogenic capsular or noncapsular polysaccharide, and where the protein or peptide SA antigens are indirectly linked via an affinity binding pair. The present SA-MAPS immunogenic compositions can elicit both humoral and cellular immune responses to the immunogenic polysaccharide and one or multiple SA antigens at the same time.

1 - 101 . (canceled) 
     
     
         102 . An immunogenic composition comprising: at least one immunogenic polysaccharide, at least two  S. aureus  peptide or polypeptide antigens, and at least one pair of affinity molecules,
 wherein the at least one pair of affinity molecules comprises a first affinity molecule and a second affinity molecule complementary to the first affinity molecule:   wherein in each pair of affinity molecules:
 the first affinity molecule is associated with the at least one immunogenic polysaccharide, 
 the second affinity molecule is associated with at least one of the  S. aureus  peptide or polypeptide antigens, and 
 the first affinity molecule non-covalently associates with the second affinity molecule to link the  S. aureus  peptide or polypeptide antigen(s) and the immunogenic polysaccharide(s); and 
   wherein the at least two  S. aureus  peptide or polypeptide antigens are each independently selected from the group consisting of: hemolysin (Hl), Clumping factor A (ClfA), Clumping factor B (ClfB), serine-aspartate repeat protein D (SdrD), serine-aspartate repeat protein E (SdrE), Iron regulator surface protein A (IsdA), Iron regulator surface protein B (IsdB), Leukotoxin D (LukD), and Leukotoxin E (LukE).   
     
     
         103 . The immunogenic composition of  claim 102 , wherein the at least two  S. aureus  peptide or polypeptide antigens are each independently selected from the group consisting of: HI, ClfA, ClfB, SdrD, IsdA, and IsdB. 
     
     
         104 . The immunogenic composition of  claim 102 , wherein the at least two  S. aureus  peptide or polypeptide antigens are each independently selected from the group consisting of: HI, ClfA, ClfB, and SdrD. 
     
     
         105 . The immunogenic composition of  claim 102 , comprising at least four  S. aureus  peptide or polypeptide antigens, wherein the at least four  S. aureus  peptide or polypeptide antigens are each independently selected from the group consisting of: hemolysin (Hl), Clumping factor A (ClfA), Clumping factor B (ClfB), serine-aspartate repeat protein D (SdrD), serine-aspartate repeat protein E (SdrE), Iron regulator surface protein A (IsdA), Iron regulator surface protein B (IsdB), Leukotoxin D (LukD), and Leukotoxin E (LukE). 
     
     
         106 . The immunogenic composition of  claim 105 , wherein the at least four  S. aureus  peptide or polypeptide antigens are or comprise HI, ClfA, ClfB, and SdrD. 
     
     
         107 . The immunogenic composition of  claim 106 , wherein the  S. aureus  Hl peptide or polypeptide antigen is or comprises a α-hemolysin (Hla), a β-hemolysin (Hlb) or a γ-hemolysin (Hl-gamma) from  S. aureus.    
     
     
         108 . The immunogenic composition of  claim 106 , wherein the  S. aureus  Hl peptide or polypeptide antigen is or comprises wildtype Hla (WT Hla) or a Hla with a reduced hemolytic activity or a non-hemolytic Hla protein. 
     
     
         109 . The immunogenic composition of  claim 106 , wherein the  S. aureus  Hl peptide or polypeptide antigen is or comprises Hla (27-319). 
     
     
         110 . The immunogenic composition of  claim 106 , wherein the  S. aureus  ClfA peptide or polypeptide antigen is or comprises ClfA (221-559). 
     
     
         111 . The immunogenic composition of  claim 106 , wherein the  S. aureus  ClfB peptide or polypeptide antigen is or comprises ClfB (203-542). 
     
     
         112 . The immunogenic composition of  claim 106 , wherein the  S. aureus  SdrD peptide or polypeptide antigen is or comprises SdrD (246-682). 
     
     
         113 . The immunogenic composition of  claim 108 , wherein the  S. aureus  Hl peptide or polypeptide antigen is or comprises the amino acid sequence of SEQ ID NO: 16, SEQ ID NO: 17, or SEQ ID NO: 18, or a polypeptide having an amino acid sequence with at least 85% sequence identity thereto. 
     
     
         114 . The immunogenic composition of  claim 110 , wherein the  S. aureus  ClfA peptide or polypeptide antigen is or comprises the amino acid sequence of SEQ ID NO: 3 or a polypeptide having an amino acid sequence with at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 3. 
     
     
         115 . The immunogenic composition of  claim 110 , wherein the  S. aureus  ClfA peptide or polypeptide antigen is or comprises an antigenic fragment having at least 30 amino acids of the amino acid sequence of SEQ ID NO: 2 or a polypeptide having at least 30 amino acids in length that has at least 85% sequence identity to said antigenic fragment. 
     
     
         116 . The immunogenic composition of  claim 111 , wherein the  S. aureus  ClfB peptide or polypeptide antigen is or comprises the amino acid sequence of SEQ ID NO: 5 or a polypeptide having an amino acid sequence with at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 5. 
     
     
         117 . The immunogenic composition of  claim 111 , wherein the  S. aureus  ClfB peptide or polypeptide antigen is or comprises an antigenic fragment having at least 30 amino acids of the amino acid sequence of SEQ ID NO: 4 or a polypeptide having at least 30 amino acids in length that has at least 85% sequence identity to said antigenic fragment. 
     
     
         118 . The immunogenic composition of  claim 112 , wherein the  S. aureus  SdrD peptide or polypeptide antigen is or comprises the amino acid sequence of SEQ ID NO: 7 or a polypeptide having an amino acid sequence with at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 7. 
     
     
         119 . The immunogenic composition of  claim 112 , wherein the  S. aureus  SdrD peptide or polypeptide antigen is or comprises an antigenic fragment having at least 30 amino acids of the amino acid sequence of SEQ ID NO: 6 or a polypeptide having at least 30 amino acids in length that has at least 85% sequence identity to said antigenic fragment. 
     
     
         120 . The immunogenic composition of  claim 102 , wherein the first affinity molecule is or comprises biotin or a derivative or mimic molecule thereof. 
     
     
         121 . The immunogenic composition of  claim 102 , wherein the first affinity molecule is a biotin derivative, lipoic acid, HABA (hydroxyazobenzene-benzoic acid) and/or dimethyl-HABA or an amine-PEG3-biotin ((+)-biotinylation-3-6, 9-trixaundecanediamine). 
     
     
         122 . The immunogenic composition of  claim 102 , wherein the second affinity molecule is or comprises a biotin-binding protein. 
     
     
         123 . The immunogenic composition of  claim 122 , wherein the biotin-binding protein is or comprises rhizavidin, avidin, streptavidin, or a homologue or derivative thereof. 
     
     
         124 . The immunogenic composition of  claim 123 , wherein the rhizavidin is or comprises the amino acid sequence of SEQ ID NO: 1, or an amino acid sequence that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 1. 
     
     
         125 . The immunogenic composition of  claim 102 , wherein the first affinity molecule is cross-linked or covalently bonded to the immunogenic polysaccharide. 
     
     
         126 . The immunogenic composition of  claim 102 , wherein the second affinity molecule is fused to one or more of the at least two  S. aureus  peptide or polypeptide antigens to form a fusion protein. 
     
     
         127 . The immunogenic composition of  claim 102 , further comprising a flexible linker peptide attached to at least one of the at least two  S. aureus  peptide or polypeptide antigens, wherein the flexible linker peptide attaches the antigens to the second affinity molecule. 
     
     
         128 . The immunogenic composition of  claim 102 , wherein the immunogenic polysaccharide is a polysaccharide selected from the group consisting of:  S. aureus , Vi polysaccharide, pneumococcal capsular polysaccharides, pneumococcal cell wall polysaccharide,  Haemophilus influenzae  Type b polysaccharide, Meningococcal polysaccharide, 0-antigens from Gram-negative bacteria, and other bacterial capsular or cell wall polysaccharides. 
     
     
         129 . The immunogenic composition of  claim 102 , wherein the immunogenic polysaccharide is selected from the group consisting of: type 1 capsular polysaccharide of  Streptococcus pneumoniae , type 5 capsular polysaccharide of  S. aureus , and type 8 capsular polysaccharide of  S. aureus.    
     
     
         130 . The immunogenic composition of  claim 102 , further comprising at least one adjuvant. 
     
     
         131 . The immunogenic composition of  claim 102  for use in any one or more of:
 a. as a diagnostic for exposure to a pathogen or immune threat, 
 b. to prevent or treat an infection by  S. aureus , or 
 c. to prevent colonization of a subject by  S. aureus.    
 
     
     
         132 . A method for inducing an immune response in a subject to  S. aureus , comprising administering to the subject the immunogenic composition of  claim 102 . 
     
     
         133 . The method of  claim 132 , wherein the subject is a human subject. 
     
     
         134 . The method of  claim 131 , wherein the immune response is to the at least one immunogenic polysaccharide and at least one of the  S. aureus  peptide or polypeptide antigens, 
     
     
         135 . The method of  claim 134 , wherein the immune response is (i) an antibody or B-cell response, or (ii) an antibody or B-cell response and T-cell response. 
     
     
         136 . The method of  claim 134 , wherein the immune response is selected from any one of the following:
 a. an immune response that is a CD4+ T cell response, including Th1, Th2, or Th17 or Th22 response, or a CD8+ T cell response, or CD4+ and CD8+ T cell response,   b. an antibody or B cell response to the at least one immunogenic polysaccharide and a CD4+ T cell response, including Th1, Th2, or Th17 or Th22 response, or a CD8+ T cell response, or CD4+/CD8+ T cell response to at least one of the  S. aureus  polypeptide antigens,   c. an antibody or B cell response to the at least one immunogenic polysaccharide, and an antibody or B cell response and a CD4+ T cell response, including Th1, Th2, Th17 or Th22 responses, or a CD8+ T cell response, or CD4+/CD8+ T cell response to at least one of the  S. aureus  peptide or polypeptide antigens, or   d. an antibody or B-cell response against at least one of the  S. aureus  peptide or polypeptide antigens which associates with the at least one immunogenic polysaccharide.   
     
     
         137 . The method of  claim 132 , wherein the immune response results in activation of INF-γ, IL-17A or IL-22 producing cells, or INF-γ, IL-17A and IL-22 producing cells.