Immunogenic composition

Abstract

The present disclosure relates to the field of Neisserial immunogenic compositions and vaccines, their manufacture and the use of such compositions in medicine. In particular the present invention relates to compositions and methods involving the factor H binding protein (fHbp) antigen. The present inventors have recognised that fHbp is poorly expressed in neisserial strains of ST269 clonal complex (a subset of strains which seems to be growing in terms of numbers of reported cases of disease attributed to it), and vaccines comprising fHbp may be made more effective against said strains by formulating the vaccine with a further antigen that can elicit protection against these strains.

1 . An immunogenic composition comprising
 (a) a first, fHbp, antigen and   (b) a second, Tdfl, antigen;   
       wherein
 (i) the first fHbp antigen is a subunit polypeptide, suitably isolated and purified to at least 50% purity, and the second Tdf I antigen is present in an outer membrane vesicle, or 
 (ii) the second Tdfl antigen is a subunit antigen, suitably isolated and purified to at least 50% purity, and first fHbp antigen is present in an outer membrane vesicle. 
 
     
     
         2 . The immunogenic composition of  claim 1 , further comprising an antigen selected from the group consisting of: Hap, Hsf and TdfH, or a combination of two or more of said antigens. 
     
     
         3 . The immunogenic composition of  claim 2 , wherein one or more of the antigens are expressed in the outer membrane vesicle. 
     
     
         4 . An immunogenic composition of  claim 1 , wherein the fHbp has at least one mutation to reduce or prevent factor H binding. 
     
     
         5 . A method for manufacture of the immunogenic composition of  claim 1 , comprising expressing at least one antigen in an outer membrane vesicle. 
     
     
         6 . The immunogenic composition of  claim 1 , wherein the one or more antigen present in the outer membrane vesicle is expressed at a higher level compared to the level of protein present in outer membrane vesicles derived from an unmodified  N. Meningitides  strain H44/76. 
     
     
         7 . The immunogenic composition of  claim 1 , wherein FrpB is present in the outer membrane vesicle at a lower level compared to the level of protein present in outer membrane vesicles derived from an unmodified  N. Meningitides.    
     
     
         8 . The immunogenic composition of  claim 1 , wherein the first antigen is combined with NadA. 
     
     
         9 . The immunogenic composition of  claim 1 , wherein the first antigen is combined with Lipo28. 
     
     
         10 . A process of producing a vaccine comprising the first antigen of the immunogenic composition of  claim 1 , comprising the step of formulating together
 (a) a first, fHbp, antigen and   (b) a second, Tdfl, antigen.