Elisabeth Wedege

The vaccine potential of meningococcal Omp85 was studied by comparing the immune responses of genetically modified deoxycholate‐extracted outer membrane vesicles, expressing five‐fold higher levels of Omp85, with wild‐type vesicles. Groups (n = 6–12) of inbred and outbred mouse strains (Balb/c, C57BL/6, OFI and NMRI) were immunized with the two vaccines, and the induced antibody levels and bactericidal and opsonic activities measured. Except for Balb/c mice, which were low responders, the genetically modified vaccine raised high Omp85 antibody levels in all mouse strains. In comparison, the wild‐type vaccine gave lower antibody levels, but NMRI mice responded to this vaccine with the same high levels as the modified vaccine in the other strains. Although the vaccines induced strain‐dependent Omp85 antibody responses, the mouse strains showed high and similar serum bactericidal titres. Titres were negligible with heterologous or PorA‐negative meningococcal target strains, demonstrating the presence of the dominant bactericidal PorA antibodies. The two vaccines induced the same opsonic titres. Thus, the genetically modified vaccine with high Omp85 antibody levels and the wild‐type vaccine induced the same levels of functional activities related to protection against meningococcal disease, suggesting that meningococcal Omp85 is a less attractive vaccine antigen.

Background: The aims of the study were to determine the molecular characteristics of a collection of Legionella pneumophila isolates from 45 cases with Legionnaires’ disease and from 96 environmental samples, received by the national reference laboratory in Norway between 2001 and 2008, to use these characteristics to identify links between cases and suspected sources of infection, and to compare the isolate characteristics with those in other European countries. Methods: The isolates were characterized by 7-gene locus sequence-based typing and dot-blotting with monoclonal antibodies to various serogroups and subgroups. Results: The clinical isolates represented 12.6% of the 357 cases notified in Norway between 2001 and 2008, during which 3 outbreaks of L. pneumophila serogroup 1 occurred. Outbreak cases constituted 62.2% of the cases, followed by travel-associated (24.4%) and sporadic cases (11.1%). Forty-two (93.3%) of the clinical and 69 (71.9%) of the environmental isolates were serogroup 1, and 39 (86.7%) and 50 (52.1%) isolates, respectively, carried the monoclonal antibody (Mab) 3/1 virulence-associated epitope. The clinical isolates belonged to 17 sequence types and the environmental isolates to 19 sequence types. neuA was not detected in 23 environmental isolates. Conclusions: Matching characteristics of sequence types and monoclonal subgroups for case and environmental isolates were obtained for all 3 outbreaks and for 2 of 5 cases of sporadic disease. Sampling during the outbreaks accounted for the higher proportion of serogroup 1 and Mab 3/1-positive environmental isolates in comparison with other European strain collections.

Following a long-distance outbreak of Legionnaires' disease from an industrial air scrubber in Norway in 2005, a seroepidemiological study measuring levels of immunoglobulin G (IgG) and IgM antibodies to Legionella pneumophila was performed with a polyvalent enzyme-linked immunosorbent assay. One year after the outbreak, IgG levels in employees ( n = 213) at the industrial plant harboring the scrubber and in blood donors ( n = 398) from the outbreak county were low but significantly higher ( P ≤ 0.002) than those in blood donors ( n = 406) from a nonexposed county. No differences in IgM levels among the three groups were found after adjustment for gender and age. Home addresses of the seroresponders in the exposed county clustered to the city of the outbreak, in contrast to the scattering of addresses of the seroresponding donors in the nonexposed county. Factory employees who operated at an open biological treatment plant had significantly higher IgG and IgM levels ( P ≤ 0.034) than those working >200 m away. Most of the healthy seroresponders among the factory employees worked near this exposure source. Immunoblotting showed that IgG and IgM antibodies in 82.1% of all seroresponders were directed to the lipopolysaccharide of the L. pneumophila serogroup 1 outbreak strain. In conclusion, 1 year after the long-distance industrial outbreak a small increase in IgG levels of the exposed population was observed. The open biological treatment plant within the industrial premises, however, constituted a short-distance exposure source of L. pneumophila for factory employees working nearby.

This study presents detailed analyses of total and specific serum antibody levels among 26 and 24 adult volunteers before vaccination and after the third dose of the meningococcal serogroup B outer membrane vesicle (OMV) vaccines MeNZB and MenBvac, respectively, in a clinical trial in New Zealand (V. Thornton, D. Lennon, K. Rasanathan, J. O'Hallahan, P. Oster, J. Stewart, S. Tilman, I. Aaberge, B. Feiring, H. Nokleby, E. Rosenqvist, K. White, S. Reid, K. Mulholland, M. J. Wakefield, and D. Martin, Vaccine 24:1395-1400, 2006). With the homologous vaccine strains as targets, both vaccines induced significant increases in serum bactericidal and opsonophagocytic activities and in the levels of immunoglobulin G (IgG) to OMV antigens in an enzyme-linked immunosorbent assay (ELISA) and to live meningococci by flow cytometry. They also induced high levels of activity against the heterologous strains, particularly in terms of opsonophagocytic activity and IgG binding to live bacteria. The antibody levels with the homologous and heterologous strains in the four assays showed high and significant positive correlations. Specific IgG binding to 10 major OMV antigens in each vaccine was measured by scanning of immunoblots; ELISAs for two antigens, lipopolysaccharide and Neisseria surface protein A (NspA), were also performed. Both vaccines elicited significant increases in IgG binding to all homologous and heterologous OMV antigens except NspA. The total IgG band intensity on the blots correlated significantly with the IgG levels determined by the OMV ELISA and flow cytometry. In conclusion, the results of the various immunological assays showed that both OMV vaccines gave rise to high levels of specific and cross-reacting antibodies.