Vaccines against Chlamydia sp.

Abstract

The present invention describes an efficient vaccine against a Chlamydia trachomatis (Ct). The vaccine is based on recombinant fusion molecules that are capable of generating a high titered neutralizing antibody response that is protective against various Ct serovars. Our invention furthermore describe the combination of these antibody promoting fragments with Ct antigens that are targets for T cells with the aim to provide a vaccine that activate both arms of the immune system.

1 . A polypeptide comprising
 a) an amino acid sequence comprising one or more surface exposed fragments of the same outer membrane protein expressed in a serotype of  Chlamydia  sp.; and   b) two or more additional amino acid sequences which is either the same sequence as defined in a) or is the corresponding surface exposed fragments from a variant of said outer membrane protein expressed in a serotype of  Chlamydia  sp., which is different from the serotype in a).   
     
     
         2 . A polypeptide according to  claim 1 , comprising three or more different amino acid sequences, where said amino acid sequences each comprise one or more surface exposed fragments from different variants of the same outer membrane protein that varies in different  Chlamydia  sp. serotypes, said amino acid sequences derived from different  Chlamydia  sp. serotypes. 
     
     
         3 . A polypeptide according to  claim 1 , comprising three or more repetitions of an amino acid sequence, where said amino acid sequence comprises one or more surface exposed fragments of the same outer membrane protein that varies in different  Chlamydia  sp. serotypes, said amino acid sequences derived from the same  Chlamydia  sp. serotype. 
     
     
         4 . A polypeptide according to  claim 1 , wherein the outer membrane protein is MOMP from any serotype. 
     
     
         5 . A polypeptide according to  claim 4 , wherein the outer membrane protein is MOMP from serotype D, E, F, G, Ia or J of  Chlamydia trachomatis  or  C. pneumoniae.    
     
     
         6 . A polypeptide according to  claim 4 , comprising one or more of the variable domains selected from 1, 2, 3, 4 of MOMP. 
     
     
         7 . A polypeptide according to  claim 6 , where the amino acid sequences are linearized. 
     
     
         8 . A polypeptide according to  claim 6 , wherein the amino acid sequences comprising the variable domains 4 (VD4) of MOMP are placed next to each other or are spaced with a linker. 
     
     
         9 . A polypeptide according to  claim 8 , comprising an amino acid sequence defined in formula I:
     xx   1 -VD4- xx   2   (Formula I)
   wherein
 VD4 is independently selected from SEQ ID NO. 15-20 or an amino acid sequence which has at least 80% sequence identity with SEQ ID NO 15-20, and 
   xx 1  consists of   i) the amino acid sequence EWQASLALSYRLNMFTPYIGVKWSRASFDADTIRIAQPK (SEQ ID NO 21) or   ii) a subsequence of the amino acid sequence in i) said subsequence comprising 1-38 amino acid residues, starting with the C-terminal K in the amino acid sequence in i)   and   xx 2  consists of   iii) the amino acid sequence DTMQIVSLQLNKMKSRKSCGIAVGTTIVDA (SEQ ID NO 22) or   iv) a subsequence of the amino acid sequence in iii) said subsequence comprising 1-29 amino acid residues, starting with the N-terminal D in the amino acid sequence in iii).   
     
     
         10 . A polypeptide according to  claim 8 , where said sequences are selected from SEQ ID NO. 23-28 and 49-59. 
     
     
         11 . A polypeptide according to  claim 1 , further comprising a fragment comprising the variable domains 1 (VD1) of MOMP and wherein the amino acid sequences comprising VD1 of MOMP are placed next to each other or are spaced with a linker. 
     
     
         12 . A polypeptide according to  claim 11  comprising an amino acid sequence defined in formula II:
     yy   1 -VD1- yy   2   (Formula II)
 
 wherein 
 VD1 is independently selected from SEQ ID NO 1-6 or an amino acid sequence which has at least 80% sequence identity with SEQ ID NO 1-6, 
 and 
 yy 1  consists of 
 v) the amino acid sequence DAISMRVGYYGDFVFDRVLKTDVNKEFQMG (SEQ ID NO 7) or 
 vi) a subsequence of the amino acid sequence in v) said subsequence comprising 1-30 amino acid residues, starting with the C-terminal G in the amino acid sequence in v) 
 and 
 yy 2  consists of 
 vii) the amino acid sequence NPAYGRHMQDAEMFTNAA (SEQ ID NO 8) or 
 viii) a subsequence of the amino acid sequence in vii) said subsequence comprising 1-18 amino acid residues, starting with the N-terminal N in the amino acid sequence in vii). 
 
     
     
         13 . A polypeptide according to  claim 11 , where said sequences are selected from SEQ ID NO. 9-14 and 45-48. 
     
     
         14 . A polypeptide according to  claim 1 , further comprising a fragment comprising the variable domains 2 (VD2) of MOMP and wherein the amino acid sequences comprising VD2 of MOMP are placed next to each other or are spaced with a linker. 
     
     
         15 . A polypeptide according to  claim 14  comprising an amino acid sequence defined in formula III:
     zz   1 -VD2- zz   2   (Formula III)
 
 wherein 
 VD2 is independently selected from SEQ ID NO 29-34 or an amino acid sequence which has at least 80% sequence identity with SEQ ID NO 29-34, 
 and 
 zz 1  consists of 
 ix) the amino acid sequence TLGATSGYLKGNSASFNLVGLFG (SEQ ID NO 35) 
 or 
 x) a subsequence of the amino acid sequence in ix) said subsequence comprising 1-23 amino acid residues, starting with the C-terminal G in the amino acid sequence in ix) 
 and 
 xx 2  consists of 
 xi) the amino acid sequence WELYTDTTFAWSVGARAALWE (SEQ ID NO 36) 
 or 
 xii) a subsequence of the amino acid sequence in xi) said subsequence comprising 1-22 amino acid residues, starting with the N-terminal V in the amino acid sequence in xi). 
 
     
     
         16 . A polypeptide according to  claim 1 , additionally comprising a fragment comprising the variable domains 3 (VD3) of MOMP and wherein the amino acid sequences comprising VD3 of MOMP are placed next to each other or are spaced with a linker. 
     
     
         17 . A polypeptide according to  claim 16  comprising an amino acid sequence defined in formula IV:
     qq   1 -VD3- qq   2   (Formula IV)
 
 wherein 
 VD3 is independently selected from SEQ ID NO 37-42 or an amino acid sequence which has at least 80% sequence identity with SEQ ID NO 37-42, 
 and 
 qq 1  consists of 
 xiii) the amino acid sequence ATLGASFQYAQSKPKVEELNVLCNAAEFTINKPKGYVG (SEQ ID NO 43) or 
 xiv) a subsequence of the amino acid sequence in xiii) said subsequence comprising 1-22 amino acid residues, starting with the C-terminal G in the amino acid sequence in xiii) 
 and 
 qq 2  consists of 
 xv) the amino acid sequence TGTKDASIDYHEWQASLALSYRLNMFTPYIGVKWS (SEQ ID NO 44) or 
 xvi) a subsequence of the amino acid sequence in xv) said subsequence comprising 1-35 amino acid residues, starting with the N-terminal T in the amino acid sequence in xv). 
 
     
     
         18 . A polypeptide according to  claim 1 , further comprising a moiety that facilitate export of the polypeptide when produced recombinantly, a moiety that facilitate purification of the fusion protein, or a moiety which enhances immunogenicity. 
     
     
         19 . A polypeptide according to  claim 18 , wherein the enhancer of immunogenicity is an additional T-cell target which is chosen from a Ct antigen such as CT043, CT004, CT414, CT681 or part hereof. 
     
     
         20 . A polypeptide according to  claim 19 , where said sequences are selected from SEQ ID NO 60-68.