In this review the results of three previous studies are compared and discussed. Sera from 101 pa... more 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 serog... more 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.
Since 1974 Norway has experienced an epidemic of meningococcal disease. In October 1986 the Natio... more Since 1974 Norway has experienced an epidemic of meningococcal disease. In October 1986 the National Institute of Public Health decided to develop and test out a vaccine against group B meningococci. This paper describes how the vaccine was tested through phase I and II trials, and how problems of safety and informed consent were handled. Two major protection trials are currently in progress. 130,000 secondary school students have volunteered for a study simulating the use of a vaccine in the long-term protection of an age group at risk. Military recruits are involved in a study where instant protection is important, as in a situation where the vaccine is used in the vicinity of an outbreak of the disease. 20,000 soldiers are included so far, and the study will ultimately include 70,000.
Cet article est un essai de revision des facteurs connus. L'etude est divisee en 3 parties: l... more Cet article est un essai de revision des facteurs connus. L'etude est divisee en 3 parties: l'agent causal: Mycobacterium leprae, la reponse de l'hote a l'infection le diagnostic des infections subcliniques
Spread of drug-resistant tuberculosis (TB) threatens TB-control programmes, and all countries nee... more Spread of drug-resistant tuberculosis (TB) threatens TB-control programmes, and all countries need to monitor the patterns and trends of anti-TB drug resistance. Such data assess the quality of control programmes and help forecast future trends of drug resistance. It will also help to establish guidelines for TB therapy. The aim of the current study was to describe the rate of drug-resistant Mycobacterium tuberculosis in the Sunamganj District of Bangladesh. Bacterial isolates were collected from sputum smear positive (ss+) patients who attended the National TB Programme from November 2003 to December 2004. A total of 95 isolates was tested for susceptibility to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) at the National Reference Laboratory for Mycobacteria at the Norwegian Institute of Public Health (NIPH), Oslo. The total resistance among new cases to any drug was 31%. For SM it was 18%, INH 23%, RMP 2%, EMB 10% and 2% were multidrug-resistant (MDR). The National Tuberculosis Programme (NTP) in Sunamganj is still effective, although the high resistance to INH is alarming. An increased risk of treatment failure has been demonstrated in areas with high levels of INH resistance, and a high proportion of INH resistant cases may develop resistance to RMP during treatment.
A reference system for M. smegmatis antigens in crossed immunoelectrophoresis was used to study a... more A reference system for M. smegmatis antigens in crossed immunoelectrophoresis was used to study antibody activities in serum samples of 91 leprosy patients. All polar and borderline lepromatous patients were positive. Mean numbers out of 14 M. smegmatis antigens involved were 4.3 and 3.5, respectively. Precipitins against antigen no. 1 were seen in all lepromatous cases. Antibodies against this antigen were detected in 50% of tuberculoid (polar, subpolar and borderline) cases. Antibody activity against M. avium and M. duvalii antigens was also detected using a staphylococcal radio-immuno-assay. Borderline and polar lepromatous cases showed elevated levels. Antigenic comparisons were made between four slow growing mycobacteria, fourteen fast growing mycobacteria and the leprosy bacillus using lepromatous serum pools as antibody reagents. Four of the antigens detected in M. leprae were also found in slow growing as well as fast growing species indicating a common occurrence among mycobacteria. Antigen no. 1 of M. duvalii, with an apparent molecular weight of 290,000, showed nonprotein characteristics. Further analysis of antigen no. 21, using lepromatous serum pools as antibody reagents, indicated the existence of at least two groups of antigenic determinants. In addition to determinants shared by all mycobacteria, there were antigenic structures apparently unique to M. leprae.
In this review the results of three previous studies are compared and discussed. Sera from 101 pa... more 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 serog... more 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.
Since 1974 Norway has experienced an epidemic of meningococcal disease. In October 1986 the Natio... more Since 1974 Norway has experienced an epidemic of meningococcal disease. In October 1986 the National Institute of Public Health decided to develop and test out a vaccine against group B meningococci. This paper describes how the vaccine was tested through phase I and II trials, and how problems of safety and informed consent were handled. Two major protection trials are currently in progress. 130,000 secondary school students have volunteered for a study simulating the use of a vaccine in the long-term protection of an age group at risk. Military recruits are involved in a study where instant protection is important, as in a situation where the vaccine is used in the vicinity of an outbreak of the disease. 20,000 soldiers are included so far, and the study will ultimately include 70,000.
Cet article est un essai de revision des facteurs connus. L'etude est divisee en 3 parties: l... more Cet article est un essai de revision des facteurs connus. L'etude est divisee en 3 parties: l'agent causal: Mycobacterium leprae, la reponse de l'hote a l'infection le diagnostic des infections subcliniques
Spread of drug-resistant tuberculosis (TB) threatens TB-control programmes, and all countries nee... more Spread of drug-resistant tuberculosis (TB) threatens TB-control programmes, and all countries need to monitor the patterns and trends of anti-TB drug resistance. Such data assess the quality of control programmes and help forecast future trends of drug resistance. It will also help to establish guidelines for TB therapy. The aim of the current study was to describe the rate of drug-resistant Mycobacterium tuberculosis in the Sunamganj District of Bangladesh. Bacterial isolates were collected from sputum smear positive (ss+) patients who attended the National TB Programme from November 2003 to December 2004. A total of 95 isolates was tested for susceptibility to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) at the National Reference Laboratory for Mycobacteria at the Norwegian Institute of Public Health (NIPH), Oslo. The total resistance among new cases to any drug was 31%. For SM it was 18%, INH 23%, RMP 2%, EMB 10% and 2% were multidrug-resistant (MDR). The National Tuberculosis Programme (NTP) in Sunamganj is still effective, although the high resistance to INH is alarming. An increased risk of treatment failure has been demonstrated in areas with high levels of INH resistance, and a high proportion of INH resistant cases may develop resistance to RMP during treatment.
A reference system for M. smegmatis antigens in crossed immunoelectrophoresis was used to study a... more A reference system for M. smegmatis antigens in crossed immunoelectrophoresis was used to study antibody activities in serum samples of 91 leprosy patients. All polar and borderline lepromatous patients were positive. Mean numbers out of 14 M. smegmatis antigens involved were 4.3 and 3.5, respectively. Precipitins against antigen no. 1 were seen in all lepromatous cases. Antibodies against this antigen were detected in 50% of tuberculoid (polar, subpolar and borderline) cases. Antibody activity against M. avium and M. duvalii antigens was also detected using a staphylococcal radio-immuno-assay. Borderline and polar lepromatous cases showed elevated levels. Antigenic comparisons were made between four slow growing mycobacteria, fourteen fast growing mycobacteria and the leprosy bacillus using lepromatous serum pools as antibody reagents. Four of the antigens detected in M. leprae were also found in slow growing as well as fast growing species indicating a common occurrence among mycobacteria. Antigen no. 1 of M. duvalii, with an apparent molecular weight of 290,000, showed nonprotein characteristics. Further analysis of antigen no. 21, using lepromatous serum pools as antibody reagents, indicated the existence of at least two groups of antigenic determinants. In addition to determinants shared by all mycobacteria, there were antigenic structures apparently unique to M. leprae.
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Papers by Gunnar Bjune