Adjuvanting meningococcal factor h binding protein

Abstract

Factor H binding protein (fHBP) has been proposed for use in immunising against serogroup B meningococcus (‘MenB’). This antigen can be efficiently adsorbed to an aluminium hydroxyphosphate adjuvant by (i) ensuring that adsorption takes place at a pH which is equal to or below the adjuvant's point of zero charge (PZC), and / or (ii) selecting a fHBP and adjuvant with an isoelectric point / PZC within the range of 5.0 to 7, and / or (iii) selecting a fHBP with an isoelectric point above the adjuvant's PZC and using a buffer to bring the pH to within 1.2 pH units of the PZC. The adsorption is particularly useful for compositions which include multiple fHBP variants, and also in situations where an aluminium hydroxide adjuvant should be avoided. Buffered pharmaceutical compositions can include at least two different meningococcal fHBP antigens, both of which are at least 85% adsorbed to aluminium hydroxyphosphate adjuvant.

Description

[0001]This application claims priority from U.S. provisional application 61 / 162,999 (filed 24 Mar. 2009), the complete contents of which are hereby incorporated herein by reference.TECHNICAL FIELD[0002]This invention is in the field of meningococcal vaccines, in particular those containing fHBP antigen.BACKGROUND ART[0003]Neisseria meningitidis (meningococcus) is a Gram-negative spherical bacterium. Current meningococcal vaccines are also based on capsular saccharides. These include monovalent serogroup C conjugate vaccines and 4-valent conjugate mixtures for serogroups A, C, W135 and Y. There is currently no useful vaccine authorised for general use against serogroup B (‘MenB’).[0004]One antigen which has been proposed for use in immunising against MenB is the factor H binding protein (fHBP). This antigen has also been called protein ‘741’ (SEQ IDs 2535 & 2536 in ref 34), ‘NMB1870’, ‘GNA1870’ [refs. 1-3], ‘P2086’, ‘LP2086’ or ‘ORF2086’ [4-6]. The protein has been well studied. It i...

AI Technical Summary

Benefits of technology

[0137]A meningococcal saccharide may comprise a full-length intact saccharide as prepared from meningococcus, and/or may comprise fragments of full-length saccharides i.e. the saccharides may be shorter than the native capsular saccharides seen in bacteria. The saccharides may thus be depolymerised, with depolym

Problems solved by technology

A problem when using aluminium hydroxide as an adjuvant, however, is that it can degrade certain antigens.

For instance, reference 10 reports that it can hydrolyse H. influenzae type B conjugate vaccines, even at low temperatures, thus leading to reduced efficacy.