Showing papers in "NIPH annals in 1991"

Vaccine against group B Neisseria meningitidis: protection trial and mass vaccination results in Cuba.

Abstract: The Cuban vaccine, first in the world with proven efficacy against group B-caused disease, is based on outer membrane proteins from B meningococci capable of inducing long-lasting and high-titered bactericidal antibodies in humans This bactericidal activity has a wide spectrum against all pathogenic group B Neisseria meningitidis tested A randomized, double-blind controlled trial of the vaccine efficacy was performed during 1987-1989 with 106,000 10-14 years old students from 197 boarding schools in seven provinces The efficacy obtained was 83% (chi 2, p less than 0002; Fischer exact, p less than 0001) In a second field trial including 133,600 persons from 5 months to 24 years of age in Ciego de Avila province (30 cases/10(5) inhabitants, the highest incidence rate in Cuba) by comparing vaccinated and non-vaccinated population after 25 years of observation and careful follow-up, the efficacy and safety was confirmed Because of these results and because of the very low reactogenicity of the vaccine, the Ministry of Public Health took the advice of the Scientific Council to vaccinate all children between 3 months and 6 years of age in the most affected provinces No severe or long lasting reactions to the vaccine were observed after the millions of doses administered The efficacy of vaccination varied in the provinces between 83% and 94%, among age groups ranging from 3 months and 20 years After 3 years of massive application no severe reactions occurred and one of the most severe epidemics has been practically eradicated

Production, characterization and control of MenB-vaccine "Folkehelsa": an outer membrane vesicle vaccine against group B meningococcal disease.

Abstract: 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.

Bactericidal antibodies after vaccination with the Norwegian meningococcal serogroup B outer membrane vesicle vaccine: a brief survey.

Abstract: Results from the serum bactericidal assay (BA) after immunization of human volunteers with the Norwegian serogroup B meningococcal outer membrane vesicle vaccine are surveyed. In the phase II trials with adults we found very high seroconversion rates (greater than 98%) against the vaccine strain in the BA. Details in the antigenic composition of the inoculum used in the BA seem very important as shown here by finding lower bactericidal titres with teenager sera when tested with a variant of the standard inoculum. The present preliminary report corresponds to the presentation given at the Report Meeting on the Norwegian Meningococcal Vaccine Trial, Oslo, 12 September, 1991.

The epidemiology of meningococcal disease in Norway 1975-91.

Abstract: The epidemiology of meningococcal disease (MCd) in Norway is described on the basis of official notification figures for 1975-91. Morbidity is presented by serogroup of the isolated Neisseria meningitidis strain, time of onset of the disease in addition to the place of living, age and sex of the patient. A long-term group B epidemic with high incidence and case fatality rates in the age groups below 5 years and between 13 and 19-20 years is the main characteristics of the situation.

Results of an efficacy trial with an outer membrane vesicle vaccine against systemic serogroup B meningococcal disease in Norway.

Abstract: A placebo controlled, double blind efficacy trial with a new outer membrane vesicle vaccine against systemic meningococcal disease of serogroup B, has been conducted in Norwegian secondary schools. The study was randomized at school level (1335 schools) and 171,800 students volunteered. The study started in October 1988 and the code was opened in June 1991. Out of the thirty-six proven cases of acute, severe, systemic disease caused by serogroup B meningococci among the participants, twelve occurred in eleven schools given vaccine, twenty-four in twenty-four schools given placebo. twenty-four cases were recorded among secondary school students who did not participate in the study. The protection rate was calculated to 57.4% with a p-value of 1.2% and lower limit of confidence (95%) to 27.7%. The results have initiated research towards an improved outer membrane vesicle vaccine against this disease.

Human antibody responses after vaccination with the Norwegian group B meningococcal outer membrane vesicle vaccine: results from ELISA studies.

Abstract: 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.

The Norwegian meningococcal serogroup B outer membrane vesicle vaccine protection trials: case tracing, meningococcal antigen detection and serological diagnosis.

Abstract: 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.

The Norwegian meningococcal group B outer membrane vesicle vaccine: side effects in phase II trials.

Abstract: 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.

Design of clinical trials with an outer membrane vesicle vaccine against systemic serogroup B meningococcal disease in Norway.

Abstract: 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.

Serum opsonins to serogroup B meningococci after disease and vaccination.

Abstract: 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.

Vaccine efficacy determination.

Abstract: The "Gold standard" in vaccine testing is the randomized, placebo controlled, double-blind efficacy trial. Once a protective immune mechanism is defined, e.g., from an efficacy trial, vaccine performance can then be judged by serologic parameters. Although immunogenicity studies can provide important information, in many instances the answer has to come from efficacy trials. For rare diseases like meningococcal disease, these trials are expensive and difficult to conduct. It is therefore incumbent to learn as much as possible from each trial. Issues in pre-licensure studies include: vaccine selection, site selection, trial design, assignment to treatment and control groups, definition and surveillance for endpoints (cases, adverse reactions), identification of surrogate markers for protection, and utilization of monitoring committees.

Development of a second generation group B meningococcal vaccine.

Abstract: Outer membrane protein vaccines have now been demonstrated to be effective in prevention of group B Neisseria meningitidis disease, but the extent and duration of protection needs improvement. To develop a second generation outer membrane protein vaccine we have begun studies to evaluate vaccines containing iron regulated proteins in lipopolysaccharide depleted outer membrane vesicles. Since the iron regulated proteins are critical for in vivo survival, it is our working hypothesis that antibodies to these proteins will either be bactericidal or block iron uptake. Four representative strains were selected, and preliminary studies indicate that vaccines containing the iron regulated proteins are immunogenic in mice.

Systemic meningococcal disease: the diagnosis on admission to hospital.

Abstract: The clinical and laboratory findings in 176 patients hospitalized with suspected systemic meningococcal disease (MCd) are presented. All except nine patients were prospectively included in the MenOPP study. One hundred and fifteen patients were most likely to have meningococcal disease, of these 71 were confirmed with growth of meningococci in blood and/or cerebrospinal fluid (CSF). The remaining sixty-one patients served as the control group. Both petechiae, reduced general condition, and reduced consciousness proved valuable in the diagnosis of MCd. Petechiae was the clinical sign best discriminating between MCd and the control group. Ecchymoses were specific for meningococcal disease. Among the laboratory tests C-reactive protein (CRP) and Thrombotest (TT) were the tests which most frequently were found to be abnormal in patients with meningococcal disease. A diagnostic score is computed by the aid of a multiple regression analysis. This score includes the variables skin hemorrhages, body pain, CSF cell count, TT, CRP and white blood cell count. For a patient hospitalized with suspected MCd a score of three or more supports the diagnosis and should indicate the need for rapid antibiotic therapy.

Comparison of two syphilis antibody assays based on cardiolipin antigen.

Abstract: Two different antisyphilis screening tests based on cardiolipin antigen, the VDRL test and an RPR test (Sysmic, Diagast), were compared. A total of 2155 sera were examined by both tests. Positive results were confirmed with TPHA and TPI tests. RPR Sysmic test was as sensitive and specific as the VDRL. However, the RPR Sysmic test was easier and quicker, especially when the number of sera tested was high.