Immunogenic composition, use and method of treatment
The present invention relates to immunogenic compositions comprising an immunogenic polypeptide from Haemophilus influenzae or an immunogenic fragment thereof and/or an immunogenic polypeptide from Moraxella catarrhalis or an immunogenic fragment thereof, for use in the treatment or prevention of a recurrence of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) resulting from a bacterial infection in a subject.
1. A method of reducing the frequency of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) associated with a bacterial infection in a subject at risk of developing an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) recurrence, said method comprising administering to said subject a therapeutically effective amount of an immunogenic composition comprising an immunogenic polypeptide from Haemophilus influenzae capable of eliciting a humoral and/or cellular immune response in a host animal, wherein the immunogenic polypeptide from Haemophilus influenzae is an amino acid sequence at least 96% identical to a reference sequence selected from SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 7 and SEQ ID NO: 9.
2. The method according to claim 1 , wherein the method further comprises identifying that the subject has previously had an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) associated with a bacterial infection before administering the immunogenic composition to the subject.
3. The method according to claim 1 , wherein the acute exacerbation of chronic obstructive pulmonary disease (AECOPD) associated with a bacterial infection is defined by:
a) a positive bacterial pathogen on culture of an induced or spontaneous sputum sample obtained from a subject; and/or
b) a total aerobic CFU count greater than or equal to 10 7 cells; and/or
c) the presence of increased sputum purulence.
4. The method according to claim 1 , wherein the acute exacerbation of chronic obstructive pulmonary disease (AECOPD) associated with a bacterial infection is defined by:
a) a positive bacterial pathogen on culture of an induced or spontaneous sputum sample obtained from a subject; and/or
b) the presence of an increased sputum purulence.
5. The method according to claim 1 , wherein the bacterial infection occurred in the presence of Haemophilus influenza or Moraxella catarrhalis.
6. The method according to claim 1 , wherein the subject has GOLD 2 (moderate), GOLD 3 (severe) or GOLD 4 (very severe) COPD status.
7. The method according to claim 1 , wherein the subject has experienced at least one (e.g. 2 or more, 3 or more) episodes of acute exacerbation in chronic obstructive pulmonary disease (AECOPD) resulting from a bacterial infection within a period of 12 months.
8. The method according to claim 1 , wherein the subject has experienced at least one (e.g. 2 or more, 3 or more) episodes of acute exacerbation in chronic obstructive pulmonary disease (AECOPD) resulting from a bacterial infection in the preceding 12 months.
9. The method according to claim 1 , wherein the subject has bronchiectasis.
10. The method according to claim 1 , wherein the subject has experienced an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) resulting from a bacterial infection and failed to achieve resolution of symptoms after antibiotic therapy.
11. The method according to claim 1 , wherein the subject is taking one or more other therapeutic agents for COPD selected from the group consisting of beta2-agonists, anticholinergics, methylxanthines, phosphodiesterase-4 (PDE-4) inhibitors and inhaled corticosteroids.
12. The method according to claim 2 , wherein the subject is a human.
13. The method according to claim 1 wherein (a) the immunogenic polypeptide from Haemophilus influenzae is selected from (i) Protein D with at least 96% sequence identity to SEQ ID NO: 2, (ii) Protein E with at least 96% sequence identity to SEQ ID NO: 5, (iii) PilA with at least 96% sequence identity to SEQ ID NO: 7, or (iv) Protein E and PilA as a fusion protein with at least 96% sequence identity to SEQ ID NO: 9.
14. The method according to claim 5 wherein the bacterial infection occurred in the presence of Haemophilus influenza.
15. The method according to claim 14 wherein the wherein the bacterial infection occurred in the presence of non-typeable Haemophilus influenzae (NTHi)).
16. The method according to claim 1 wherein the immunogenic composition further comprises an immunogenic polypeptide from Moraxella catarrhalis capable of eliciting a humoral and/or cellular immune response in a host animal, wherein the immunogenic polypeptide from Moraxella catarrhalis is an amino acid sequence at least 96% identical to a reference sequence selected from MC-009 (SEQ ID NO. 19), MC-010 (SEQ ID NO. 20) or MC-011 (SEQ ID NO. 21).
17. The method according to claim 16 wherein the immunogenic polypeptide from Moraxella catarrhalis is an amino acid sequence at least 96% identical to SEQ ID NO. 19.