To evaluate whether the observed bactericidal activity of mAb Me-1 is not limited to a particular group of strains, we are presently evaluating its activity against a larger panel of serologically distinct meningococcal strains in the presence of human match

To evaluate whether the observed bactericidal activity of mAb Me-1 is not limited to a particular group of strains, we are presently evaluating its activity against a larger panel of serologically distinct meningococcal strains in the presence of human match. the affinity-purified recombinant NspA protein efficiently guarded 80% of the mice SSR128129E against a meningococcal fatal challenge comparatively to the 20% observed in the control groups. The fact that this NspA protein can elicit the production of bactericidal and protective antibodies emphasize its potential as a vaccine candidate. causes both endemic and epidemic diseases, principally meningitidis and meningococcemia (1, 2). This pathogenic bacteria primarily affects young children between SSR128129E 6 mo and 2 yr of age, but often infects teenagers (1). The incidence per year of meningococcal diseases during endemic periods is normally 1C3 cases per 100,000 in developed countries, but it can be as high as 500 per 100,000 during epidemics (2, 3). is usually classified into 12 serogroups based on the immunological characteristics of the capsular polysaccharides found at their surface. Within serogroups, different serotypes, subtypes, and immunotypes can be identified based on the antigenic specificity of the major outer membrane (OM)1 proteins and LPS (4). Approximately 90% of all meningococcal diseases worldwide are caused by isolates of serogroups A, B, and C (5). Vaccines based on the capsular polysaccharides of serogroups A, C, W-135, and Y were developed and proved efficient to control outbreaks and epidemics of meningococcal diseases (6). However, these vaccines are poorly immunogenic in very young children. Moreover, they do not induce immunological memory and the period of the protection they provide is usually relatively short (5, 7C11). Recently, it was exhibited that conjugation of capsular polysaccharides of serogroups A and C to carrier proteins resulted in a better immunogenicity and a longer persistence of specific antibodies against isolates of these serogroups (12C16). Attempts to develop an efficient vaccine against serogroup B isolates, which are responsible for 50C70% of the meningococcal disease in the developed countries were unsuccessful because the group B capsular polysaccharide is not a good immunogen in human, inducing only a poor IgM response of low specificity which is not protective (17C19). Furthermore, the presence of closely similar, cross-reactive structures in the glycoproteins of neonatal human brain tissue might discourage attempts to improve the immunogenicity of serogroup B polysaccharide (10). To develop a vaccine effective against meningococci of serogroup B several non-capsular surface structures are under investigation (6, 10). Importantly, the presence of bactericidal antibodies against have been strongly correlated with human immunity and protection (20C22). For that reason, it is believed that non-capsular surface antigens shown to stimulate bactericidal antibodies should be considered as the prime vaccines candidates (6). Early studies using sera of immunized volunteers and convalescent patients indicated that certain meningococcal surface SSR128129E proteins such as the ones responsible for serotype specificity and LPS could induce bactericidal antibodies and be involved in protection (23, 24). mAbs were then used to clearly establish the protective potential of certain meningococcal major surface proteins such as the PorA (class 1), PorB (class 2/3), and Opc (class 5C) (25C28). Different vaccines based on OM proteins were recently evaluated in clinical trials and efficiency between 50 and 80% were recorded (6, 10). These first generation OM proteins vaccines often induced protection against a limited number of strains. Thus, these vaccines could be used during meningococcal epidemics when the antigenic variation of the meningococci causing diseases is relatively low. The specificity of the bactericidal antibodies induced by these vaccines was determined to be directed mainly against PorA and Opc proteins (29, 30). However, the PorA-specific bactericidal antibodies were found to be directed against epitopes located in surface-exposed highly variable regions (31). Moreover, the Mouse monoclonal to CD62P.4AW12 reacts with P-selectin, a platelet activation dependent granule-external membrane protein (PADGEM). CD62P is expressed on platelets, megakaryocytes and endothelial cell surface and is upgraded on activated platelets.This molecule mediates rolling of platelets on endothelial cells and rolling of leukocytes on the surface of activated endothelial cells Opc protein was shown to be produced by only 60% of strains of different serogroups.