Method for adjuvanting lipopolysaccharide (LPS) of Gram-negative bacteria

Abstract

The subject of the invention is a method for adjuvanting LPS of a Gram-negative bacterium, according to which LPS or LPS liposomes (LPS formulated in liposomes) is (are) mixed with the lipidated human-transferrin receptor subunit B (TbpB protein) of Neisseria meningitidis or a lipidated fragment thereof or (ii) LPS and the lipidated TbpB of N. meningitidis or a lipidated fragment thereof are formulated together in liposomes; or (iii) LPS is conjugated with the lipidated TbpB of N. meningitidis or a lipidated fragment thereof in order to obtain a preparation which does not contain OMVs and which is capable of inducing, after administration to a mammal, an anti-LPS immune response which is improved by comparison with the anti-LPS immune response observed after administration of the corresponding preparation in which the lipidated TbpB of N. meningitidis or a lipidated fragment thereof is omitted; as well as vaccine compositions thereof. The LPS may, for example, be the LOS of a non-enteric Gram-negative bacterium such as N. meningitidis.

What is claimed is: 
     
         1 . A vaccine which does not contain outer membrane vesicles (OMVs) and which comprises (i) a vaccine antigen which is the lipopolysaccharide (LPS) from a Gram-negative bacterium, optionally formulated in liposomes, conjugated to a carrier polypeptide or in an endotoxoid form, and (ii) an adjuvant of the anti-LPS immune response, which is the lipidated human-transferrin receptor subunit B (TbpB protein) of  N. meningitidis  or a lipidated fragment thereof the LPS being present in sufficient amount for the anti-LPS immune response induced by the vaccine to be capable of protecting an individual against a disease caused by the Gram-negative bacterium. 
     
     
         2 . The vaccine as claimed in  claim 5 , in which the LPS is the LOS of  N. meningitidis.    
     
     
         3 . The vaccine as claimed in  claim 6 , in which the LPS is the LOS of a  N. meningitidis  L8 immunotype. 
     
     
         4 . The vaccine as claimed in  claim 7 , in which the LPS is the LOS of  N. meningitidis  strain A1. 
     
     
         5 . The vaccine as claimed in  claim 5 , in which the LPS is formulated in liposomes. 
     
     
         6 . The vaccine as claimed in  claim 5 , in which the LPS and the lipidated TbpB of  N. meningitidis  or a lipidated fragment thereof are formulated together in liposomes. 
     
     
         7 . The vaccine as claimed in  claim 5 , in which the LPS is in endotoxoid form. 
     
     
         8 . The vaccine as claimed in  claim 5 , in which the LPS is conjugated to a carrier polypeptide. 
     
     
         9 . The vaccine as claimed in  claim 5 , in which the LPS is conjugated to the lipidated TbpB of  N. meningitidis  or a lipidated fragment thereof. 
     
     
         10 . The vaccine as claimed in  claim 5 , which does not contain any adjuvant compound other than the LPS and the lipidated TbpB of  N. meningitidis  or a lipidated fragment thereof.