Assessment of natural and outer membrane vesicle (OMV) vaccine induced immunity against Neisseria meningitidis serogroup B in an infant rat infection model
Year: 2005
Type: dissertation
Abstract: Background: Despite of the amount of work on the meningococcal serogroup B bacteria and immunity to disease caused by them, a satisfactory vaccine for these important pathogens is still missing. Several group B meningococcal vaccines based on outer membrane protein vesicles (OMV) or complexes have been evaluated in phase II and III clinical trials. Although the antibody responses in connection with these phase III clinical protection trials and separate immunogenicity trials have been analyzed extensively by enzyme immunosorbent assay (EIA) and by assays for serum bactericidal (SBA) and opsonophagocidal activity, the specificity and the functional activity of antibodies providing protection against serogroup B disease is still partly open. The lack of reliable laboratory correlates or surrogates for protection has hampered vaccine development against this important pathogen. Study aims: The main aim of the present study was evaluate the applicability of an infant rat protective activity (IRPA) assay to assess meningococcal serogroup B OMV vaccine responses induced in humans. To this end, preand post-vaccination serum samples from teenagers immunized with two doses of either the Norwegian OMV vaccine (MenBvacTM), the Cuban OMV vaccine (VA-MENGOC-BCTM), or the serogroup A/C capsular PS control vaccine during a previous immunogenicity trial in Iceland were analyzed for IRPA, and the results compared to SBA and EIA data obtained with the same serum set and vaccine efficacy data obtained earlier in different study populations. We also studied the specificity and functional activity of natural antibodies conferring protection in this animal model. Wellcharacterized Mabs were used to assess the influence of antibody specificity and isotype on protection, and complement component C6 deficient animals to evaluate the importance of complement-mediated bacterial lysis on protection. Results and conclusions: As compared to the results from rises in anti-OMV IgG levels measured by EIA and to a lesser extent also in SBA titres, the numbers of vaccine responders detected in IRPA assay were only modest. Thus, although likely to be useful for the preclinical evaluation of candidate MenB vaccines, the IRPA assay, as described herein, is probably less suitable for large-scale evaluation of serogroup B OMV vaccine responses in clinical samples. Despite this limitation, the IRPA assay seemed to give some additional value over the SBA assay in that many SBA negative pre-vaccination sera were often IRPA positive though many SBA positive sera remained IRPA negative. In sera taken before vaccination the IRPA against strain 44/76-SL was mainly mediated by serogroup B capsular specific IgM antibody and was independent of complement-mediated bacterial lysis as evident from the lack of SBA in vitro and equal protective activity of normal human sera in complement sufficient and C6 deficient animals. Studies with serogroup B capsular specific antibody of mouse origin confirmed the latter finding. These findings were in contrast to PorA protein specific IgG antibodies whose protective activity in C6 deficient animals was severely impaired. A clear connection between the acquisition of natural B-PS specific IgM antibodies and IRPA was also indicated. These results suggest that importance capsular PS specific antibodies on protective immunity against serogroup B disease may have been
Source: Työväentutkimus Vuosikirja
Author: Maija Toropainen
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2162874648