Search PubMed⌕ Search

Biomedical subjects

G Bjune

Publications and source records attributed to G Bjune.

At least 19 recordsLinked to original sources
PubMed1998

A mouse model for latent tuberculosis.

The aim of the study was to establish a reproducible murine model for latent tuberculosis. We propose an operational definition of latent murine tuberculosis as a stable Mycobacterium-tuberculosis count in lungs and spleens without clinical signs or obvious histopathological changes in the lungs over a long period of time and without spontaneous reactivation of disease. B6D2F1Bom mice were inoculated with a wide range of Mycobacterium tuberculosis doses intraperitoneally or intravenously and followed for a long period to determine suitable conditions to produce latent infection. No anti-tuberculosis drug treatment was used. Microbiological and histopathological studies were carried out. Corticosterone challenge was used to reactivate the latent infection. Mice infected with 4 x 10(4) and 4 x 10(5) bacilli i.p. were followed up to 107 weeks without spontaneous reactivation. The present model is discussed in comparison with previous latent tuberculosis mouse models as well as the possible mechanisms of shift to stationary phase from multiplying bacilli.

Animals↗
PubMed1998

Immune responses against major outer membrane antigens of Neisseria meningitidis in vaccinees and controls who contracted meningococcal disease during the Norwegian serogroup B protection trial.

Sera from vaccinees and controls who contracted serogroup B meningococcal disease during the blinded and open parts of a two-dose protection trial in Norway were compared for antigen-specific and bactericidal antibodies against vaccine strain 44/76 (B:15:P1.7,16). From 16 of 20 (80%) vaccinees and 26 of 35 (74%) controls, one or more serum samples (n = 104) were collected during the acute phase (1 to 4 days), early convalescent phase (5 to 79 days), and late convalescent phase (8 to 31 months) after onset of disease. Binding of immunoglobulin G (IgG) to the major outer membrane antigens (80- and 70-kDa proteins, class 1, 3, and 5 proteins, and lipopolysaccharide [LPS]) on immunoblots was measured by digital image analysis. Specific IgG levels in vaccinees increased from acute to early convalescent phases, followed by a decline, while controls showed a small increase over time. Vaccinees had significantly higher levels than controls against class 1 and 3 porins and LPS in acute sera, against all antigens during early convalescence, and against class 1 and 3 porins in the later sera. Vaccinees who were infected with strains expressing subtype P1.7,16 proteins demonstrated a level of IgG binding to protein P1.7,16 with early-convalescent-phase sera that was fourfold higher than that of those infected with other strains. Bactericidal titers in serum against the vaccine strain were 192-fold higher for vaccinees than those for controls during early convalescence, but similarly low levels were found during late convalescence. A vaccine-induced anamnestic response of specific and functional antibody activities was thus shown, but the decrease in protection over time after vaccination indicated that two vaccine doses did not induce sufficient levels of long-term protective antibodies.

Antibodies, Bacterial↗
PubMed1998

Effect of aluminium hydroxide and meningococcal serogroup C capsular polysaccharide on the immunogenicity and reactogenicity of a group B Neisseria meningitidis outer membrane vesicle vaccine.

Three different formulations of an outer membrane vesicle (OMV) vaccine against group B meningococcal disease have been prepared and tested for immunogenicity and reactogenicity in adult volunteers. The vaccines were prepared with or without aluminium hydroxide and serogroup C-polysaccharide (C-ps). Doses from 12.5 to 100 micrograms protein were given twice at a six weeks' interval. All three formulations were well tolerated and highly immunogenic, inducing bactericidal and opsonizing antibodies in humans. Adsorption of OMVs to aluminium hydroxide reduced the pyrogenicity in rabbits. The differences in immunogenicity between the formulations were relatively small, but after the second dose a stronger booster response was observed when the vaccines were adsorbed. Thus, a formulation with OMVs and C-ps represents a safe and highly immunogenic vaccine, even without aluminium hydroxide.

Adjuvants, Immunologic↗
PubMed1997

Lipopolysaccharide heterogeneity and escape mechanisms of Neisseria meningitidis: possible consequences for vaccine development.

We wanted to compare the potential protective capacity of antibodies to meningococcal lipopolysaccharides (LPS). The frequency of occurrence and degree of expression of the epitopes recognized by murine monoclonal antibodies (MAbs) to immunotypes L3,7,9 (9-2-L379) and L8 (2-1-L8) and to the LPS inner core (216-Lc and 217-Lc), were determined among 77 consecutive Norwegian meningococcal patient isolates from 1995. The immunotype L3,7,9 was strongly expressed by 95% of the isolates, whereas L8 was weakly to moderately expressed by 9%. The inner core epitopes, were widely distributed among the serogroup B organisms, but were proved weakly expressed. The bactericidal activity of the four MAbs to various selected strains, was found to correlate positively with the quantity of the LPS epitopes recognized by these four MAbs in the bacteria. When tested in the serum bactericidal assay (SBA), often a few percent of the colonies of the inocula survived high concentrations of the MAbs. The results indicate that escape from the bactericidal action could be achieved through: (i) selection of variants not expressing the LPS-epitope of the actual MAb, (ii) a relative reduction in the density of the LPS-epitope achieved by dilution with another LPS structure or (iii) other factors, not yet understood. In conclusion, antibodies to the L3,7,9 epitope seem to be of importance for protection, whereas antibodies to the epitopes of the LPS inner core or immunotype L8, are not likely to offer protection alone. However, in order to prevent escape through alteration of the LPS pattern of the microbes, various LPS structures should probably be present in the OMV vaccine.

Animals↗
PubMed1997

Outer membrane vesicle vaccines made from short-chain lipopolysaccharide mutants of serogroup B Neisseria meningitidis: effect of the carbohydrate chain length on the immune response.

Outer membrane vesicle (OMV) vaccines were made from Neisseria meningitidis strain 44/76 and its two short-chain lipopolysaccharide (LPS) mutants, Mu-1 and Mu-4. Only the 44/76 vaccine contained LPS with the host antigen lacto-N-neotetraose. The protein composition of the vaccines was similar. The LPS carbohydrate chain length proved to influence drastic changes in the LPS immunogenicity as well as the outer membrane proteins (OMPs) ability to elicit functional antibodies in mice. Only LPS in the Mu-1 and Mu-4 vaccines were immunogenic, and the 44/76 vaccine differed also by not inducing antibodies to the class 4 OMP. The Mu-1 vaccine, with a LPS carbohydrate chain comprising only two residues of 2-keto-3-deoxy-octonic acid, induced lower bactericidal activity and less antibodies to the class 1 OMP, compared to the two other vaccines. This indicates that LPS of a certain carbohydrate chain length is required for adequate exposure of the class 1 OMP epitopes essential for inducing bactericidal antibodies.

Animals↗
PubMed1995

[New vaccines. What can we expect in the coming years?].

There is an urgent need for new vaccines. The biotechnological revolution has created new hope. However, developments are hampered by inadequate basic knowledge about the immunology of infections, and lack of coordination between public and commercial research and development work on vaccines. Recombinant vaccines are an important step forward when combined with new adjuvants, but the authorization of these adjuvants for use in humans has been slow. Recombinant live vectors for vaccine antigens circumvent this problem, but imply some risk in HIV-infected people. Nucleic acid vaccines are met with strong emotional resistance, because of many unanswered questions as to their safety. Mucosal vaccines make quality control simpler, open up for a safer use of live recombinant vectors and simplify delivery of the vaccine. New vaccines marketed in the last decade are surprisingly "old-fashioned". Traditional ways of making vaccines have still not been abandoned.

Bacterial Vaccines↗
PubMed1995

Short-chain lipopolysaccharide mutants of serogroup B Neisseria meningitidis of potential value for production of outer membrane vesicle vaccines.

Four lipopolysaccharide (LPS) mutants (Mu-1 to Mu-4) were isolated after exposing Neisseria meningitidis strain 44/76 to pyocins from Pseudomonas aeruginosa. Parent strain LPS contained one major SDS-PAGE band expressing the immunotype determinants of L3, L3,7 and L3,7,9 and a minor band of higher mobility expressing the immunotype determinants of L8, L8a, L1,8,10 and L11. Each mutant LPS appeared as one SDS-PAGE band of higher mobility than the bands of the parent strain. None of these LPSs expressed the immunotype determinants of the parent strain, except Mu-4 LPS which reacted with the L11-specific MAb 4C4. Strain 44/76 LPS was found to contain galactose (Gal), glucose (Glc), heptose (Hep), glucosamine (GlcN), and 2-keto-3-deoxy-octulosonic acid (Kdo) in the molar ratios of 1.9:1.3:1.7:3.5:2.1. The corresponding ratios of the mutants were: Mu-4, 0:1.7:1.7:2.8:2.0; Mu-3, 0:0:1.7:2.4:1.6; Mu-2, 0:0:2.1:1.8:2.0, Mu-1, 0:0:1.8:1.9. Thus, all mutant LPSs lacked Gal and possessed less GlcN as compared to strain 44/76 LPS. Consequently, these mutants do not express the lacto-N-neo-tetraose (Gal1-4GlcN1-3Gal1-4Glc) commonly found as a part of meningococcal LPS and also on structures of human erythrocytes. These LPS mutants will be considered for use in production of OMV vaccines without host-like antigens, which might favour induction of antibodies to more conserved epitopes of meningococcal LPS.

Antibodies, Bacterial↗
PubMed1995

Human antibody responses to meningococcal outer membrane antigens after three doses of the Norwegian group B meningococcal vaccine.

The antibody kinetics in sera from 27 adults after three doses of the Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine was studied. The vaccinees received the third dose 4 to 5 years after the first two. Antibody responses against outer membrane proteins (OMPs) and lipopolysaccharides were studied by enzyme-linked immunosorbent assay and immunoblotting and with serum bactericidal assays (SBA) with three variants of the vaccine strain, 44/76. Six weeks after the second injection, the geometric mean (GM) of the levels of immunoglobulin G (IgG) against OMVs was about sevenfold higher than that of prevaccination levels, and 74% of the vaccinees developed a greater-than-twofold rise in SBA titer. After 6 months, the GM of IgG levels declined to about threefold higher, and after 4 to 5 years it declined to about twofold higher, than that before vaccination. The third dose induced a rapid increase in SBA titers in 96% of the vaccinees, and the GM of levels of IgG against OMVs rose to about 14-fold the prevaccination level. One year later, the IgG antibody levels had dropped to 4.6-fold the prevaccination level, but 88% of the vaccinees still showed bactericidal activity. The response after the two first doses was higher in individuals with prevaccination antibodies, but no such effect was found after three doses. The use of defined mutants in SBA and linear multiple regression analyses indicated that among the major OMPs, antibodies to the Opc and class 1 proteins made the most important single contributions to the bactericidal activity against the vaccine strain, but it also demonstrated the importance of antibodies against other antigens. After three doses, 68% of the vaccinees showed a significant SBA response against a strain lacking both the Opc and the class 1 proteins. Three doses converted almost all subjects to SBA responders and gave higher antibody levels and relatively less serosubtype-specific bactericidal activity than did two doses, probably indicating a broader cross-protection against heterologous strains.

Adult↗
PubMed1995

Comparison among opsonic activity, antimeningococcal immunoglobulin G response, and serum bactericidal activity against meningococci in sera from vaccinees after immunization with a serogroup B outer membrane vesicle vaccine.

Opsonic activity in sera from 27 military recruits vaccinated with the Norwegian meningococcal serogroup B outer membrane vesicle vaccine was measured as respiratory burst with polymorphonuclear leukocytes as the effector cells and meningococci of the epidemic strain as the target. The results were compared with antimeningococcal IgG antibodies against an outer membrane vesicle coat in an enzyme-linked immunosorbent assay and with serum bactericidal activity. The vaccinees were immunized twice, with a 6-week interval between the two. The serum samples studied were collected at day zero, after 6 weeks, and after 12 weeks. Both serum bactericidal activity and respiratory burst were measured by adding external serum as the complement source. The results revealed a significant increase in specific IgG response, serum bactericidal activity, and respiratory burst after vaccination. We found a highly significant correlation between the responses in all three assays (P < 0.0001). The highest correlation was found between respiratory burst and antimeningococcal IgG response (r = 0.93). This result strongly indicates that respiratory burst is mediated almost exclusively by IgG antibodies. The correlation between antimeningococcal IgG response and serum bactericidal activity was slightly lower (r = 0.83). The correlation between respiratory burst and serum bactericidal activity was further reduced (r = 0.78), and some of the sera revealed a marked preference for only one of the activities. This result means that respiratory burst and serum bactericidal activity in part are induced by different mediators, and to obtain a more complete picture of the potential protective activity, both assays should be applied to survey a vaccine trial.

Adult↗
PubMed1994

[The global tuberculosis problem. An apparition from history?].

Tuberculosis is increasing, partly because of concomitant HIV-infection, but with poverty and lack of social welfare and public health services contributing substantially. Current treatment for tuberculosis has proved efficacious also in HIV-infected patients, and so far seems to have prevented increased transmission of the disease in Tanzania. Strictly controlled chemotherapy provides the only hope of preventing the emergence of multi-resistant tubercle bacilli. The World Bank has evaluated tuberculosis control as the most cost-effective form of health intervention among adults. Norway has made a substantial contribution to the development of a model for tuberculosis control in developing countries and to international mycobacterial research; and therefore has a special responsibility to meet the new challenge.

Africa↗
PubMed1994

Comparison of the class-1 outer membrane protein from B:15:P1.16 Neisseria meningitidis strains isolated from patients previously immunized with a serogroup B outer membrane protein vaccine in Norway.

A previous report of a large, double blind, efficacy trial of an experimental Group B meningococcal outer membrane protein vaccine carried out in Norwegian Teenagers, showed a protection rate of 57%. Previous studies had demonstrated the occurrence of mutations in the class-1 outer membrane protein which alter its immunological properties. The occurrence of new mutations might compromise the efficacy of a vaccine and explain the occurrence of any vaccine failures. The porA gene, which encodes expression of the class 1 protein, was sequenced in all isolates from vaccine failures and compared to that of the vaccinating strain H44/76 (B:15:P1.7,16). The porA DNA and deduced amino acid sequences were all identical to that of the vaccinating strain except for that of one isolate which had a sequence identical to strains previously reported in Norway and England with a 'masked P1.7' epitope. The absence of new mutations in the trial was encouraging for the further development of outer membrane protein vaccines.

Adolescent↗
PubMed1994

Sensitivity and specificity of PCR for detection of Mycobacterium tuberculosis: a blind comparison study among seven laboratories.

PCR is, in principle, a simple and rapid test for use in the detection of Mycobacterium tuberculosis. However, virtually no data are available on the reliability and reproducibility of the method. In order to assess the validity of PCR for the detection of mycobacteria in clinical samples, seven laboratories participated in a blinded study of 200 sputum, saliva, and water samples containing either known numbers of Mycobacterium bovis BCG cells or no added organisms. Each laboratory used its own protocol for pretreatment, DNA extraction, and detection of the amplification product. Insertion sequence IS6110 was the target for DNA amplification. Several participating laboratories reported high levels of false-positive PCR results, with rates ranging from 3 to 20% and with one extreme value of 77%. The levels of sensitivity also ranged widely among the different participants. A positive PCR result was reported for 2 to 90% of the samples with 10(3) mycobacteria. Although most participants did include control tests to check the sensitivity and specificity of the PCR, the sequence of operations from sample pretreatment to purification of DNA from bacteria was not always monitored adequately. During these procedures cross-contaminating DNA was introduced and/or bacterial DNA was lost. The results of the study show that the implementation of an effective system for monitoring sensitivity and specificity is required before the PCR can be used reliably in the diagnosis of tuberculosis.

Base Sequence↗
PubMed1994

Asymptomatic carriage of Neisseria meningitidis in a randomly sampled population.

To estimate the extent of meningococcal carriage in the Norwegian population and to investigate the relationship of several characteristics of the population to the carrier state, 1,500 individuals living in rural and small-town areas near Oslo were selected at random from the Norwegian National Population Registry. These persons were asked to complete a questionnaire and to volunteer for a bacteriological tonsillopharyngeal swab sampling. Sixty-three percent of the selected persons participated in the survey. Ninety-one (9.6%) of the volunteers harbored Neisseria meningitidis. The isolates were serogrouped, serotyped, tested for antibiotic resistance, and analyzed by multilocus enzyme electrophoresis. Eight (8.8%) of the 91 isolates represented clones of the two clone complexes that have been responsible for most of the systemic meningococal disease in Norway in the 1980s. Age between 15 and 24, male sex, and active and passive smoking were found to be independently associated with meningococcal carriage in logistic regression analyses. Working outside the home and having an occupation in transportation or industry also increased the risk for meningococcal carriage in individuals older than 17, when corrections for gender and smoking were made. Assuming that our sample is representative of the Norwegian population, we estimated that about 40,000 individuals in Norway are asymptomatic carriers of isolates with epidemic potential. Thus, carriage eradication among close contacts of persons with systemic disease is unlikely to have a significant impact on the overall epidemiological situation.

Adolescent↗
PubMed1993

A low serum concentration of mannan-binding protein is not associated with serogroup B or C meningococcal disease.

The mammalian C-type serum lectin, mannan-binding protein (MBP), may induce C1q- and antibody-independent activation of the classical pathway of complement. Accordingly, MBP is considered as a member of the complement system. Complement deficiencies have been found with increased frequency in patients with meningococcal disease. Therefore, we investigated the MBP levels in patients with meningococcal disease. Ninety-nine Norwegian individuals (age 12-21 years) who survived severe systemic disease caused by serogroup B or C meningococci were investigated. No significant differences were observed in the MBP concentration between patients with serogroup B (n = 76) or C (n = 25) disease and healthy blood donor controls (n = 40) (P > 0.05). The frequency of patients with low levels of MBP (< 100 micrograms/l) was 10.1%. This was not different from controls (12.5%). Thus, low MBP concentrations do not appear to predispose to serogroup B or C meningococcal disease.

Adolescent↗
PubMed1993

Low prevalence of complement deficiencies among patients with meningococcal disease in Norway.

Sera from 98 individuals who had survived meningococcal disease were analysed for classical and alternative pathway haemolytic activity and the complement components C3, C4 and properdin. No complete deficiency was found. However, median properdin concentration was only 86% in the disease group compared with the controls (P < 0.001). Properdin was also significantly lower in serogroup C disease (median 76%) compared with serogroup B disease (median 90%, P = 0.005). Severe properdin deficiency is an established risk factor for meningococcal disease. The present data may indicate that even moderately reduced properdin level can increase the risk of developing meningococcal disease.

Adolescent↗
PubMed1991

Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway.

For more than 15 years, Norway has had the highest incidence of meningococcal disease in northern Europe, with 80% of cases being due to serogroup B meningococci. The case-fatality has remained high, at about 10%. In this study, an outer membrane vaccine, which had previously been shown to induce an increase in bactericidal antibodies to the parent strain, was assessed in a large-scale, randomised, double-blind trial. From October, 1988, 171,800 students in secondary schools volunteered to take part in a double-blind, placebo-controlled, efficacy trial with school as the randomisation unit. Hospitals and clinics that routinely receive patients with infectious disease were asked to report urgently all cases of suspected meningitis and/or septicaemia in 13-21-year-old students in Norway. These cases were registered and further investigated according to a detailed protocol. 89 out of the 221 cases investigated by June 3, 1991, were shown to be severe systemic disease due to group B meningococci. 36 cases in 35 schools took part in the trial (11 schools with vaccinated students and 24 with students given placebo). The calculated rate of protection was thus 57.2% (p = 0.012, one-sided test). The findings suggest that, although the vaccine conferred protection against group B meningococcal disease, the effect was insufficient to justify a public vaccination programme.

Adolescent↗