Vaccine for nontypeable haemophilus influenzae infection

Abstract

This invention provides a method for identifying strains of nontypeable Haemophilus influenzae that can be used as immunogenic compositions having specificity against a plurality of Haemophilus influenzae strains. The invention also provides compositions comprising whole cell bacteria or outer membrane protein P2 obtained from the strains for use as vaccines.

1 . An immunogenic composition comprising whole cell bacteria from at least five strains of nontypeable  Haemophilus influenzae  (NTHI), wherein each of the strains can elicit an immune response against at least one NTHI strain not included in the immunogenic composition. 
   
   
       2 . The immunogenic composition of  claim 1 , wherein each of the strains can elicit an immune response against at least two NTHI strains not included in the immunogenic composition. 
   
   
       3 . The immunogenic composition of  claim 1 , wherein each of the strains can elicit an immune response against at least three NTHI strains not included in the immunogenic composition. 
   
   
       4 . The immunogenic composition of  claim 1 , wherein the composition can elicit an immune response against at least ten NTHI strains not included in the immunogenic composition. 
   
   
       5 . The immunogenic composition of  claim 1 , wherein the composition can elicit an immune response against at least 70% of strains from a diverse population of cells, wherein the diverse population of cells is obtained from at least 100 individuals. 
   
   
       6 . The immunogenic composition of  claim 1 , further comprising an adjuvant. 
   
   
       7 . The immunogenic composition of  claim 1 , wherein the strains are selected from the group consisting of 13P24H1, 23P2H1, 54P24H1, 47P12H1, 31P7H1, 32P8H2 and 6P5H. 
   
   
       8 . A method for designing immunogenic compositions having cross reactivity against a plurality of nontypeable  Haemophilus influenzae  (NTHI) strains comprising the steps of:
 a) obtaining amino acid sequences of NTHI outer membrane protein 2 (OMP P2) proteins from a plurality of NTHI strains;   b) comparing the sequences and constructing a relatedness tree;   c) grouping the strains based on degrees of relatedness of the OMP P2 amino acid sequences;   d) from the groups of step c), selecting one or more representative strains having high degrees of OMP P2 amino acid sequence relatedness to other strains in the group from which the representative is selected;   e) testing the selected representative strains to identify representative strains with high degrees of cross-reactivity to a plurality of NTHI strains; and   f) preparing an immunogenic composition comprising whole cell bacteria from the representative strains identified in step e) or OMP P2 proteins derived from the representative strains identified in step e).   
   
   
       9 . The method of  claim 8 , wherein the immunogenic composition comprises at least five NTHI strains or OMP P2 proteins derived from at least five NTHI strains. 
   
   
       10 . The method of  claim 8 , wherein the immunogenic composition can elicit an immune response against at least ten NTHI strains not included in the immunogenic composition or against at least ten NTHI strains from which the OMP P2 proteins in the composition were not derived.