The Neisseria meningitidis macrophage infectivity potentiator (MIP) protein induces cross-strain serum bactericidal activity and is a potential serogroup B vaccine candidate

A gene encoding a 29kDa protein from Neisseria meningitidis serogroup B strain MC58, with homology to the macrophage infectivity potentiator (MIP) protein of Legionella pneumophila was cloned and expressed in Escherichia coli and the purified soluble recombinant protein (rMIP) was used for immunisation studies. Analysis of the predicted amino acid sequences of MIP from 13 well-characterised meningococcal strains, isolated from carriers or patients, and differing in serogroup, serotype and subtype, showed that the protein was highly conserved (98-100%) with only three distinct sequence types found (designated I, II and III). Western blotting showed that the MIP protein was expressed at similar levels by all of these strains. Immunisation of mice with type I MC58 rMIP in detergent micelles and liposomes containing monophosphoryl lipid A (MPLA) induced high levels of surface-reactive antibodies with serum bactericidal activity (SBA) titres of 1/1024 against the homologous strain. Bactericidal antibodies were also induced with the protein in saline alone and liposomes alone (titres of 1/128), but not following adsorption to Al(OH)3. Significantly, antisera raised against type I rMIP administered in saline or liposomes killed strains of heterologous sequence types II and III, with similar SBA titres (1/128-256). Taken together, these findings suggest that rMIP can provide cross-strain protection against meningococci and should be considered as a potential antigen for inclusion in new vaccines against meningococcal infection

Pneumococcal 6-phosphogluconate-dehydrogenase, a putative adhesin, induces protective immune response in mice

For most bacteria, adherence to human cells is achieved by bacterial lectins binding to mammalian surface glyconjugates. 6-Phosphogluconate dehydrogenase (6PGD) was identified by us as one of Streptococcus pneumoniae cell wall lectin proteins, which elicits an age-dependent immune response in humans. This study assesses the role of 6PGD in S. pneumoniae pathogenesis as an adhesin and its ability to elicit a protective immune response in mice. Recombinant 6PGD (r6PGD) was cloned from S. pneumoniae serotype 3 (strain WU2). r6PGD interference in adhesion of three genetically unrelated unencapsulated pneumococcal strains (3·8, 14·8 and R6) and two genetically unrelated encapsulated pneumococcal strains (WU2 and D39) to A549 type II lung carcinoma cell was tested. BALB/c mice were immunized with r6PGD and boosted after 3 weeks. Immunized mice were challenged intranasally with a lethal dose of S. pneumoniae. r6PGD inhibited 90% and 80% of pneumococcal adhesion to the A549 cells of three unencapsulated S. pneumoniae strains and two encapsulated S. pneumoniae strains, respectively, in a concentration-dependent manner (P< 0·05). Antibodies to r6PGD produced in mice significantly inhibited bacterial adhesion to A549 cell (P< 0·05). Immunization of mice with r6PGD protected 60% (P< 0·001) of mice for 5 days and 40% (P< 0·05) of the mice for 21 days following intranasal lethal challenge. We have identified 6PGD as a surface-located immunogenic lectin protein capable of acting as an adhesin. 6PGD importance to bacterial pathogenesis was demonstrated by the ability of r6PGD to elicit a protective immune response in mice