NIPH annals最新文献

A survey is given of the efforts made to inform the general public, the potential vaccinees and their parents, and the health care personnel about meningococcal disease in general and the vaccination trial in particular, as a preparation for the meningococcal outer membrane vesicle serogroup B vaccine (MenB-vaccine "Folkehelsa") trials in secondary school students and military conscripts in Norway. Our case reporting system, supplementing the official notification, concerning even vaguely suspected cases in the age cohorts involved, is described. The efforts made to collect clinical material as well as laboratory and clinical data from 221 registered suspected cases are delineated. We also briefly summarize our cerebrospinal fluid antigen detection methods and diagnostic meningococcal serology work on these suspected cases. The compiled information on findings done at the admitting hospital of the possible cases and the additional diagnostic data provided at the National Institute of Public Health were put at the disposal of the independent Diagnosis Review Committee (DRC) as a basis for their diagnostic decisions before code opening for the meningococcal serogroup B outer membrane vesicle vaccine protection trial 3 June 1991.

Antibody responses after vaccination with three different formulations of a new meningococcal group B outer membrane vesicle (OMV) vaccine have been studied with the ELISA technique using four different antigens. Sera from about 1200 vaccinees participating in steps 1, 2, 3 and 6 of the phase II clinical trials in Norway were analysed. The effects of non-covalently complexing the OMV antigen to group C polysaccharide (C-PS) and of adsorbing OMV (with and without C-PS) to aluminium hydroxide (AH) were studied. All three vaccine formulations were highly immunogenic in humans. Adsorption of the vaccine to AH had a relatively small effect on the immune response, but the results indicated that the booster response was stronger with the adsorbed than with the unadsorbed vaccines. Some increase in the immune response against OMV was also observed by non-covalent complexing OMV with C-PS, particularly after the second dose. In most of the vaccinees the antibody levels were significantly reduced 6 to 12 months after vaccination. Adsorption of the vaccine to AH had no effect on the antibody response against C-PS. Comparison with bactericidal activity of the same sera was done. A highly significant correlation was observed between the bactericidal titres and the levels of IgG antibodies against OMV and class 5C protein, whereas the correlation between antibody levels against lipopolysaccharide and the bactericidal activity was poor.

In order to establish the safety of the Norwegian meningococcus B vaccine we have focused on detailed reporting of side effects in several phase II trials. We report here the results of the largest single phase II study, (step II-6) including 877 school children. The incidence of local side effects was significantly higher in the vaccine than in the placebo group, but most of them were mild and short-lasting. Mild systemic side effects were commonly reported in both groups, but more severe side effects were rare and almost equally distributed between the groups.

A vaccine against serogroup B meningococcal disease has been prepared from a B:15:P1.7,16 meningococcal strain (44/76) by fermentor growth and extraction of the bacteria with the detergent deoxycholate. Outer membrane vesicles (OMV) were purified by ultracentrifugation and adsorbed to aluminium hydroxide adjuvant. OMV contained the major class 1, 3, 4 and 5 proteins and some minor high molecular weight protein components. Relative to protein, the vaccine also contained about 8% phospholipid, 7% lipopolysaccharide and 16% deoxycholate. The product was generally non-pyrogenic to humans in ordinary doses and was highly immunogenic in mice and humans. Production and control steps, physical, chemical and immunological data for the vaccine are described.

In this review the results of three previous studies are compared and discussed. Sera from 101 patients with meningococcal disease and from 113 volunteers immunized twice with vaccine preparations against serogroup B meningococci were examined for antimeningococcal opsonic activity using a chemiluminescence (CL) method. Twelve groups of vaccinees were immunized twice with one of four different doses of an outer membrane vesicle (OMV) preparation either alone or complexed to serogroup C polysaccharide and/or the adjuvant Al(OH)3. The OMV vaccine strain (44/76) was a patient isolate characterized as B:15:P1.16. The 89 surviving patients and 97/113 volunteers responded with significantly increased opsonic activity to the vaccine strain. Sera from all vaccinees with low preimmunization levels demonstrated a significant postimmunization increase in opsonic activity. The vaccine response was dose related, and the second injection induced a booster response in those who received preparations containing Al(OH)3. At 26 weeks a reduction in opsonic activity to preimmunization levels was noted in 19/97 previous responders. The reduction was less pronounced in those who were immunized with the higher doses. Using CL and flow cytometry we found vaccinee sera to show cross reacting opsonin responses to other serogroups and serotypes of meningococci except meningococci of serotype 2a and 2b. The increase in antimeningococcal opsonins after vaccination suggests that the serogroup B OMV vaccine may induce protection against clinical disease.

An outer membrane vesicle vaccine against acute, systemic disease caused by meningococci of serogroup B has been developed. The vaccine has been tested consecutively in phase I and phase II clinical trials including more than 5000 volunteers. These trials provided data on safety, immunogenicity and reactogenicity and possible effect on carriage of meningococci in the throat, and consequently formed the basis for two major protection trials; one in secondary school students and one among military recruits. The aims, design and major results of phase I and phase II studies are described as well as the design and organization of the protection trials.