Compositions and methods for immunization against drug resistant acinetobacter baumannii

Abstract

The present invention provides vaccine compositions comprising OmpA, or antigenic fragments thereof, and related methods of active immunization against A. baumannii infection. The invention also provides antibodies and antigen-binding parts thereof that specifically bind to OmpA, and related methods of passive immunization against A. baumannii infection. The compositions and methods of the invention are useful for preventing or treating A. baumannii infections, including those caused by strains resistant to carbapenems and all other antibiotics except colistin or tigecycline, also referred to as extreme drug resistant (XDR) A. baumannii infections, and those resistant to every FDA approved antibiotic, also referred to as pan-drug resistant (PDR) A. baumannii infections.

1 - 27 . (canceled) 
     
     
         28 . A composition comprising an antibody, or antigen binding fragment thereof, wherein said antibody or antigen binding fragment specifically binds to an epitope encoded by an amino acid sequence selected from SEQ ID NOS:1-6. 
     
     
         29 . The composition of  claim 28 , wherein said epitope consists of at least 10 but less than 25 amino acids in length and an amino acid sequence of SEQ ID NOS:1-6 that comprises:
 (i) the asparagine at position 91;   (ii) the serine at position 28; or   (iii) the alanine at position 163.   
     
     
         30 . The composition of  claim 29 , wherein said epitope consists of at least 10 but less than 20 amino acids in length. 
     
     
         31 . The composition of  claim 29 , wherein said epitope consists of at least 10 but less than 15 amino acids in length. 
     
     
         32 . The composition of  claim 29 , further comprising a pharmaceutically acceptable carrier. 
     
     
         33 . A method of prophylactic or therapeutic treatment of  A. baumannii  infection in a subject, comprising administering to the subject:
 (i) a composition comprising an antibody, or antigen binding fragment thereof, wherein said antibody or antigen binding fragment specifically binds to an epitope encoded by an amino acid sequence selected from SEQ ID NOS:1-6; or   (ii) an immunologically effective amount of a vaccine composition comprising an  A. baumannii  outer membrane protein A (OmpA), or an antigenic fragment thereof, wherein said OmpA is at least 80% identical to SEQ ID NOS:1-6.   
     
     
         34 . The method of  claim 33 , wherein said epitope or said antigenic fragment consists of at least 10 but less than 25 amino acids in length and an amino acid sequence of SEQ ID NOS:1-6 that comprises:
 (i) the aspartic acid at position 123, the aspartic acid at position 125, and the asparagine at position 128;   (ii) the asparagine at position 91;   (iii) the serine at position 28; or   (iv) the alanine at position 163.   
     
     
         35 . The method of  claim 34 , wherein said epitope or said antigenic fragment consists of at least 10 but less than 20 amino acids in length. 
     
     
         36 . The method of  claim 34 , wherein said epitope or said antigenic fragment consists of at least 10 but less than 15 amino acids in length. 
     
     
         37 . The method of  claim 33 , wherein the subject is a human. 
     
     
         38 . An isolated polypeptide comprising an amino acid sequence selected from SEQ ID NOS:1-6 or an antigenic fragment thereof. 
     
     
         39 . The isolated polypeptide of  claim 38 , wherein said antigenic fragment consists of at least 10 but less than 25 amino acids in length and an amino acid sequence of SEQ ID NOS:1-6 that comprises:
 (i) the aspartic acid at position 123, the aspartic acid at position 125, and the asparagine at position 128;   (ii) the asparagine at position 91;   (iii) the serine at position 28; or   (iv) the alanine at position 163.   
     
     
         40 . The isolated polypeptide of  claim 39 , wherein said antigenic fragment consists of at least 10 but less than 20 amino acids in length. 
     
     
         41 . The isolated polypeptide of  claim 39 , wherein said antigenic fragment consists of at least 10 but less than 15 amino acids in length. 
     
     
         42 . A vaccine composition comprising the isolated polypeptide of  claim 38  and a pharmaceutically acceptable carrier. 
     
     
         43 . The vaccine composition of  claim 42 , wherein said composition further comprises an adjuvant. 
     
     
         44 . An isolated nucleic acid molecule encoding the isolated polypeptide, or the antigenic fragment thereof, of  claim 38 . 
     
     
         45 . A vector comprising the isolated nucleic acid molecule of  claim 44 . 
     
     
         46 . A vaccine composition comprising the vector of  claim 45 .