Vaccine against acinetobacter baumannii based on cellular components deficient in lipopolysaccharide

Abstract

The invention refers to a composition comprising inactivated cells deficient in LPS from the genus Acinetobacter and/or outer membrane vesicles form the same and their use for the manufacture of a medicament, preferably a vaccine, for the prevention of diseases produced by organisms of the genus Acinetobacter.

1 . A vaccine composition suitable for the prophylactic treatment of an infection caused by an  Acinetobacter baumannii  strain in a mammal, which comprises:
 a. an  Acinetobacter baumannii  strain deficient in lipopolysaccharide (LPS) characterized by the partial or complete inactivation of one or various cellular nucleic acid molecules that encode endogenous LPS; and/or   b. an outer membrane vesicle (OMV) derived from an  Acinetobacter baumannii  strain deficient in lipopolysaccharide (LPS) as defined in paragraph a) above.   
     
     
         2 . The vaccine composition of  claim 1 , wherein the  Acinetobacter baumannii  strain deficient in lipopolysaccharide (LPS) is characterized by the partial or complete inactivation of one or more genes selected from the group consisting of IpxA, IpxB and IpxC. 
     
     
         3 . The vaccine composition of  claim 1 , wherein said vaccine further comprises a recombinant polypeptide selected from the group consisting of:
 a. An amino acid sequence SEQ ID NO: 27 (putative ferric siderophore receptor ( A. baumannii  ATCC 17978; accession number YP_001084684)) or a fragment thereof, wherein the fragment is a biologically active fragment selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 11 or any combination thereof, and an amino acid sequence having at least 85% identity with any of sequences SEQ ID NO: 1 to SEQ ID NO: 11; and   b. An amino acid sequence SEQ ID NO: 28 (putative ferric hydroximate siderophore receptor ( A. baumannii  ATCC 17978; accession number YP_001084696)) or a fragment thereof, wherein the fragment is a biologically active fragment selected from the group consisting of SEQ ID NO: 12 to SEQ ID NO: 23 or any combination thereof, and sequences that have at least 85% identity with the amino acids SEQ ID NO: 12 to SEC ID NO: 23.   
     
     
         4 . The vaccine composition of  claim 1 , that further comprises a purified outer membrane protein sequence of  A. baumannii  selected from the group consisting of: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46; SEQ ID NO: 47; SEQ ID NO: 48; SEQ ID NO: 49; SEQ ID NO: 50; SEQ ID NO: 51; SEQ ID NO: 52; SEQ ID NO: 53; SEQ ID NO: 54; SEQ ID NO: 55; SEQ ID NO: 56; SEQ ID NO: 57; SEQ ID NO: 58; SEQ ID NO: 59; SEQ ID NO: 60; SEQ ID NO: 61; SEQ ID NO: 62; SEQ ID NO: 63; SEQ ID NO: 64; SEQ ID NO: 65; SEQ ID NO: 66; SEQ ID NO: 67; SEQ ID NO: 68; SEQ ID NO: 69; SEQ ID NO: 70; SEQ ID NO: 71; SEQ ID NO: 72; SEQ ID NO: 73; SEQ ID NO: 74; SEQ ID NO: 75; SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID No: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, and any combination thereof. 
     
     
         5 . The vaccine composition of  claim 1 , wherein said vaccine further comprises the fusion recombinant polypeptide of SEQ ID NO: 24 or 25 or the fusion recombinant polypeptide coded by the nucleic acid molecule of SEQ ID NO: 26. 
     
     
         6 . The vaccine composition of  claim 3 , wherein the  Acinetobacter baumannii  strain deficient in lipopolysaccharide (LPS) comprises or is transformed, transduced or transfected with a nucleotide sequence capable of coding for any of the amino acid sequences as defined in  claim 3  so that such strain is capable of producing the exogenous expression any of said amino acid sequences. 
     
     
         7 . The vaccine composition of  claim 3 , wherein said vaccine composition further comprises a vector, such as viral vector, a plasmid or an expression cassette comprising a nucleotide sequence capable of coding for any of the amino acid sequences as defined in  claim 3  and expressing said amino acid sequences. 
     
     
         8 . The vaccine composition of  claim 1 , wherein said  Acinetobacter baumannii  strain deficient in lipopolysaccharide (LPS) is inactivated. 
     
     
         9 . The vaccine composition of  claim 1 , wherein the  Acinetobacter baumannii  strain deficient in lipopolysaccharide (LPS) is derived from ATCC strain 19606. 
     
     
         10 . (canceled) 
     
     
         11 . A vaccine composition comprising an antibody (monoclonal or polyclonal) or a fragment thereof selected from the group list consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , Vhh, nanobody and diabody, capable of specifically binding the  Acinetobacter baumannii  strain deficient in lipopolysaccharide (LPS) and/or the outer membrane vesicle (OMV) derived therefrom as defined in  claim 1 . 
     
     
         12 . A vaccine composition comprising an isolated antibody (monoclonal or polyclonal) or a fragment thereof selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , Vhh, nanobody and diabody, obtained or obtainable after immunizing a mammal with the vaccine composition as defined in  claim 1 . 
     
     
         13 . (canceled) 
     
     
         14 . An  Acinetobacter baumannii  strain deficient in lipopolysaccharide (LPS) characterized by the partial or complete inactivation of one or various cellular nucleic acid molecules that encode endogenous LPS, optionally by the partial or complete inactivation of one or more genes selected from the group consisting of IpxA, IpxB and IpxC, transformed, transduced or transfected with a nucleotide sequence capable of coding for any of the amino acid sequences as defined in  claim 3  so that such strain is capable of producing the exogenous expression any of said amino acid sequences. 
     
     
         15 . An  Acinetobacter baumannii  strain deficient in lipopolysaccharide (LPS) as defined in  claim 1 , for use as a medicament. 
     
     
         16 . A method for the production of antibodies or fragments thereof, optionally selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′)2, Vhh, nanobody and diabody, which comprises:
 Selecting an antibody or a fragment thereof, optionally from an antibody library; 
 Using an  Acinetobacter baumannii  strain deficient in lipopolysaccharide (LPS) and/or an outer membrane vesicle (OMV) derived therefrom, as an antigenic target; 
 Selecting those antibodies or fragments thereof having affinity or binding affinity or capable of specifically binding such strain and/or OMV; and 
 Producing those antibodies or fragments thereof identified in step c) above. 
 
     
     
         17 . (canceled) 
     
     
         18 . A method for prophylactic treatment of an infection caused by  A. baumannii  in a mammal, comprising
 administering the vaccine composition of  claim 1  to the mammal having an infection caused by  A. baumannii , optionally wherein the mammal is a human.   
     
     
         19 . A method for therapeutic treatment (after infection) of an infection caused by  A. baumannii  in a mammal, comprising
 administering the vaccine composition of  claim 11  to the mammal having an infection caused by  A. baumannii , optionally wherein the mammal is a human.