E Rosenqvist

Norwegian Institute of Public Health, Kristiania (historical), Oslo County, Norway

Are you E Rosenqvist?

Claim your profile

Publications (75)241.56 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Meningococcal meningitis is a significant global health challenge, especially for sub-Saharan area: the African meningitis belt. Neisseria meningitidis of serogroup A (MenA) is responsible for the large number of epidemics that have been recorded in these countries. To determine the level of antibodies against meningococcal A polysaccharide (APS) that correlates with protection against MenA disease in the African meningitis belt, it may be important to consider antibody avidity along with quantity. In this study two ELISA methods using the chaotropic agent ammonium thiocyanate were compared and employed to measure avidity indexes (AI) of IgG antibodies against APS in controls and in acute and convalescent sera from Ethiopian meningococcal patients High statistical correlations between the AIs determined by the two methods were observed. The geometric mean AI (GMAI) increased with time from acute to convalescent sera indicating affinity maturation. GMAI was significantly higher in convalescent sera from the MenA patients and in sera from the controls than in acute sera from patients with meningococcal disease. A significant correlation between serum bactericidal activity titres (SBA) and concentration of IgG antibodies against APS was observed; however, our results did not indicate that determination of antibody avidities by the thiocyanate elution method gave a better correlation with SBA than anti-APS IgG concentrations determined by the standard ELISA method. This article is protected by copyright. All rights reserved.
    Scandinavian Journal of Immunology 01/2014; · 2.20 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Meningococci of serogroups A and W (MenA and MenW) are the main causes of epidemic bacterial meningitis outbreaks in sub-Saharan Africa. In this study we prepared a detergent extracted outer membrane vesicle (dOMV) vaccine from representative African MenA and MenW strains, and compared the immunogenicity of this vaccine with existing meningococcal conjugate and polysaccharide (PS) vaccines in mice. NMRI mice were immunized with preclinical batches of the A+W dOMV vaccine, or with commercially available vaccines; a MenA conjugate vaccine (MenAfriVac(®), Serum Institute of India), ACYW conjugate vaccine (Menveo(®), Novartis) or ACYW PS vaccine (Mencevax(®), GlaxoSmithKline). The mice received 2 doses of 1/10 or 1/50 of a human dose with a three week interval. Immune responses were tested in ELISA, serum bactericidal activity (SBA) and opsonophagocytic activity (OPA) assays. High levels of IgG antibodies against both A and W dOMV were detected in mice receiving the A+W dOMV vaccine. High SBA titers against both MenA and MenW vaccine strains were detected after only one dose of the A+W dOMV vaccine, and the titers were further increased after the second dose. The SBA and OPA titers in mice immunized with dOMV vaccine were significantly higher than in mice immunized with the ACYW-conjugate vaccine or the PS vaccine. Furthermore, the A+W dOMV vaccine was shown to induce SBA and OPA titers against MenA of the same magnitude as the titers induced by the A-conjugate vaccine. In conclusion, the A+W dOMV vaccine induced high levels of functional antibodies to both MenA and MenW strains, levels that were shown to be higher or equal to the levels induced by licensed meningococcal vaccines. Thus, an A+W dOMV vaccine could potentially serve as an alternative or a supplement to existing conjugate and PS vaccines in the African meningitis belt.
    Vaccine 10/2013; · 3.77 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: The utility of wild-type outer membrane vesicle (wtOMV) vaccines against serogroup B (MenB) meningococcal disease has been explored since the 1970s. Public health interventions in Cuba, Norway and New Zealand have demonstrated that these protein-based vaccines can prevent MenB disease. Data from large clinical studies and retrospective statistical analyses in New Zealand give effectiveness estimates of at least 70%. A consistent pattern of moderately reactogenic and safe vaccines has been seen with the use of approximately 60 million doses of three different wtOMV vaccine formulations. The key limitation of conventional wtOMV vaccines is their lack of broad protective activity against the large diversity of MenB strains circulating globally. The public health intervention in New Zealand (between 2004-2008) when MeNZB was used to control a clonal MenB epidemic, provided a number of new insights regarding international and public-private collaboration, vaccine safety surveillance, vaccine effectiveness estimates and communication to the public. The experience with wtOMV vaccines also provide important information for the next generation of MenB vaccines designed to give more comprehensive protection against multiple strains.
    Human vaccines & immunotherapeutics. 03/2013; 9(6).
  • [show abstract] [hide abstract]
    ABSTRACT: The bacterium Neisseria meningitidis of serogroups A and W-135 has in the recent decade caused most of the cases of meningococcal meningitis in the African meningitis belt, and there is currently no efficient and affordable vaccine available demonstrated to protect against both these serogroups. Previously, deoxycholate-extracted outer membrane vesicle (OMV) vaccines against serogroup B meningococci have been shown to be safe and induce protection in humans in clonal outbreaks. The serogroup A and W-135 strains isolated from meningitis belt epidemics demonstrate strikingly limited variation in major surface-exposed protein structures. We have here investigated whether the OMV vaccine strategy also can be applied to prevent both serogroups A and W-135 meningococcal disease. A novel vaccine combining OMV extracted from recent African serogroup A and W-135 strains and adsorbed to aluminium hydroxide was developed and its antigenic characteristics and immunogenicity were studied in mice. The specificity of the antibody responses was analysed by immunoblotting and serum bactericidal activity (SBA) assays. Moreover, the bivalent A+W-135 vaccine was compared with monovalent A and W-135 OMV vaccines. The bivalent OMV vaccine was able to induce similar SBA titres as the monovalent A or W-135 OMV towards both serogroups. High SBA titres were also observed against a meningococcal serogroup C strain. These results show that subcapsular antigens may be of importance when developing broadly protective and affordable vaccines for the meningitis belt.
    Scandinavian Journal of Immunology 04/2012; 76(2):99-107. · 2.20 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: In the absence of an affordable conjugate meningococcal vaccine, mass vaccination campaigns with polysaccharide vaccines are the means to control meningitis epidemics in sub-Saharan Africa. Facing global vaccine shortage, the use of reduced doses, which have been shown to be protective by serum bactericidal activity, can save many lives. In this study, we investigated the antibody responses and avidity of IgG antibodies evoked against the serogroup A capsule of Neisseria meningitidis by different doses of an A/C/Y/W135 polysaccharide vaccine. Volunteers in Uganda were vaccinated with 1/10, 1/5 or a full dose (50 μg) and revaccinated with a full dose after 1 year. Specific IgG geometric mean concentrations and geometric mean avidity indices (GMAI) were determined by a modified enzyme-linked immunosorbent assay (ELISA) using thiocyanate as a chaotropic agent. After vaccination with 1/10 or 1/5 doses, the GMAI increased from 1 month to 1 year. One year following the initial dose, the GMAI levels were higher in the arm receiving reduced doses than for the arm receiving a full dose. Following the second full dose, avidity indices equalized at approximately the same level in the three arms. Although there are practical challenges to the use of reduced doses in the field, our findings suggest that reduced doses of polysaccharide vaccine are able to elicit antibodies of as good avidity against serogroup A polysaccharide as a full dose.
    Scandinavian Journal of Immunology 02/2011; 74(1):87-94. · 2.20 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: IgG and IgG subclass antibodies to the outer membrane antigens from Neisseria meningitidis (serogroup B., serotype 15:P1.16) were quantitated by an enzyme-linked immunosorbent assay (ELISA) in sera from 40 patients with group B:15:P1.16 meningococcal disease and 24 volunteers immunized with a serotype 15:P1.16 outer membrane vesicle vaccine. A second injection was given 6 weeks after the first immunization. Patient sera obtained two and six weeks after onset of the disease had significantly higher levels of total IgG, IgG1, IgG2, and IgG3 antibodies to the outer membrane antigens than acute sera, convalescent sera from patients with systemic non-meningococcal bacterial infections and sera from healthy controls. The levels of total IgG and IgG 1 remained high one and three years later. Sera from the vaccinees showed high levels of total IgG and IgG 1 6, 12 and 26 weeks after the first immunization and high levels of IgG3 6 weeks after the second immunization. No increase of IgG2 or IgG4 levels was observed in the postimmunization sera. Immunoblotting of three convalescent sera demonstrated individual patterns of IgG subclass binding to various outer membrane antigens with most distinct binding of IgG 1 and IgG3 antibodies to the class 1 protein, the H.8 lipoprotein and the lipopolysaccharide. Since IgGl and IgG3 are the most effective antibodies for complement activation and phagocytosis, group B meningococcal disease and immunization with the serotype 15:P1.16 outer membrane vesicle vaccine stimulate production of those IgG subclasses which have the strongest opsonic and bactericidal activity.
    Apmis 08/2009; 98(7‐12):1061 - 1069. · 2.07 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Meningococcal outer membrane proteins have been used for over 20 years in more than 80 million doses; either as carrier protein in a Haemophilus influenzae type b (Hib) polysaccharide conjugate vaccine or as vesicle vaccine formulations against meningococcal disease. Conventional wild-type outer membrane vesicle (wtOMV) vaccines are the only formulations that have shown efficacy against serogroup B meningococcal disease. This has been demonstrated in Cuba, Norway and New Zealand; where epidemics, dominated by one particular strain or clone, were causing high rates of disease and wtOMV vaccines have been used for epidemic control. The most significant limitation for widespread use of wtOMV is that the immune response is strain-specific in infants, mostly directed against the immuno-dominant porin protein, PorA. The natural orientation of surface-exposed membrane antigens and the preservation of good physico-chemical stability are key features of OMV vaccines. The efficacy, tolerability and safety of wtOMV vaccines have been well proven. The most recent experience from New Zealand demonstrated a vaccine effectiveness of 80% for children less than 5 years of age, over a period of 24 months. Such results are encouraging for the further use of "tailor-made" OMV vaccines for epidemic control. Moreover, it provides opportunities for development of OMV vaccines with various additional cross-protective potential. There is good reason to believe that in the coming few years the "OMV-concept" will be exploited further and that a number of cross-protective "universal" antigens will be included in vaccines against serogroup B meningococcal disease. The desire to have a global vaccine strategy that enables susceptible individuals to be protected against all the relevant serogroups of meningococcal disease may become a reality.
    Vaccine 06/2009; 27 Suppl 2:B3-12. · 3.77 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Neisseria meningitidis serogroup A is the main causative pathogen of meningitis epidemics in sub-Saharan Africa. In recent years, serogroup W135 has also been the cause of epidemics. Mass vaccination campaigns with polysaccharide vaccines are key elements in controlling these epidemics. Facing global vaccine shortage, we explored the use of fractional doses of a licensed A/C/Y/W135 polysaccharide meningococcal vaccine. We conducted a randomized, non-inferiority trial in 750 healthy volunteers 2-19 years old in Mbarara, Uganda, to compare the immune response of the full dose of the vaccine versus fractional doses (1/5 or 1/10). Safety and tolerability data were collected for all subjects during the 4 weeks following the injection. Pre- and post-vaccination sera were analyzed by measuring serum bactericidal activity (SBA) with baby rabbit complement. A responder was defined as a subject with a > or =4-fold increase in SBA against a target strain from each serogroup and SBA titer > or =128. For serogroup W135, 94% and 97% of the vaccinees in the 1/5- and 1/10-dose arms, respectively, were responders, versus 94% in the full-dose arm; for serogroup A, 92% and 88% were responders, respectively, versus 95%. Non-inferiority was demonstrated between the full dose and both fractional doses in SBA seroresponse against serogroups W135 and Y, in total population analysis. Non-inferiority was shown between the full and 1/5 doses for serogroup A in the population non-immune prior to vaccination. Non-inferiority was not shown for any of the fractionate doses for serogroup C. Safety and tolerability data were favourable, as observed in other studies. While the advent of conjugate A vaccine is anticipated to largely contribute to control serogroup A outbreaks in Africa, the scale-up of its production will not cover the entire "Meningitis Belt" target population for at least the next 3 to 5 years. In view of the current shortage of meningococcal vaccines for Africa, the use of 1/5 fractional doses should be considered as an alternative in mass vaccination campaigns. ClinicalTrials.gov NCT00271479.
    PLoS Neglected Tropical Diseases 01/2009; 2(12):e342. · 4.57 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Dissecting the specificities of human antibody responses following disease caused by serogroup A meningococci may be important for the development of improved vaccines. We performed a study of Ethiopian patients during outbreaks in 2002 and 2003. Sera were obtained from 71 patients with meningitis caused by bacteria of sequence type 7, as confirmed by PCR or culture, and from 113 Ethiopian controls. Antibody specificities were analyzed by immunoblotting (IB) against outer membrane antigen extracts of a reference strain and of the patients' own isolates and by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) levels against lipooligosaccharide (LOS) L11 and the proteins NadA and NspA. IB revealed that the main antigens targeted were the proteins PorA, PorB, RmpM, and Opa/OpcA, as well as LOS. MenA disease induced significant increases in IgG against LOS L11 and NadA. The IgG levels against LOS remained elevated following disease, whereas the IgG anti-NadA levels returned to acute-phase levels in the late convalescent phase. Among adults, the anti-LOS IgG levels were similar in acute-phase patient sera as in control sera, whereas anti-NadA IgG levels were significantly higher in acute-phase sera than in controls. The IgG antibody levels against LOS and NadA correlated moderately but significantly with serum bactericidal activity against MenA strains. Future studies on immune response during MenA disease should take into account the high levels of anti-MenA polysaccharide IgG commonly found in the population and seek to clarify the role of antibodies against subcapsular antigens in protection against MenA disease.
    Clinical and vaccine Immunology: CVI 06/2008; 15(5):863-71. · 2.60 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Dissecting the specificities of human antibody responses following disease caused by serogroup A meningococci may be important for the development of improved vaccines. We performed a study of Ethiopian patients during outbreaks in 2002 and 2003. Sera were obtained from 71 patients with meningitis caused by bacteria of sequence type 7, as confirmed by PCR or culture, and from 113 Ethiopian controls. Antibody specificities were analyzed by immunoblotting (IB) against outer membrane antigen extracts of a reference strain and of the patients' own isolates and by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) levels against lipooligosaccharide (LOS) L11 and the proteins NadA and NspA. IB revealed that the main antigens targeted were the proteins PorA, PorB, RmpM, and Opa/OpcA, as well as LOS. MenA disease induced significant increases in IgG against LOS L11 and NadA. The IgG levels against LOS remained elevated following disease, whereas the IgG anti-NadA levels returned to acute-phase levels in the late convalescent phase. Among adults, the anti-LOS IgG levels were similar in acute-phase patient sera as in control sera, whereas anti-NadA IgG levels were significantly higher in acute-phase sera than in controls. The IgG antibody levels against LOS and NadA correlated moderately but significantly with serum bactericidal activity against MenA strains. Future studies on immune response during MenA disease should take into account the high levels of anti-MenA polysaccharide IgG commonly found in the population and seek to clarify the role of antibodies against subcapsular antigens in protection against MenA disease.
    Clin Vaccine Immunol. 01/2008; 15(5):863-71.
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: MenBvac and MeNZB are safe and efficacious vaccines against serogroup B meningococcal disease. MenBvac is prepared from a B:15:P1.7,16 meningococcal strain (strain 44/76), and MeNZB is prepared from a B:4:P1.7-2,4 strain (strain NZ98/254). At 6-week intervals, healthy adults received three doses of MenBvac (25 microg), MeNZB (25 microg), or the MenBvac and MeNZB (doses of 12.5 microg of each vaccine) vaccines combined, followed by a booster 1 year later. Two-thirds of the subjects who received a monovalent vaccine in the primary schedule received the other monovalent vaccine as a booster dose. The immune responses to the combined vaccine were of the same magnitude as the homologous responses to each individual vaccine observed. At 6 weeks after the third dose, 77% and 87% of the subjects in the combined vaccine group achieved serum bactericidal titers of > or = 4 against strains 44/76 and NZ98/254, respectively, and 97% and 93% of the subjects achieved a fourfold or greater increase in opsonophagocytic activity against strains 44/76 and NZ98/254, respectively. For both strains, a trend of higher responses after the booster dose was observed in all groups receiving at least one dose of the respective strain-specific vaccine. Local and systemic reactions were common in all vaccine groups. Most reactions were mild or moderate in intensity, and there were no vaccine-related serious adverse events. The safety profile of the combined vaccine was not different from those of the separate monovalent vaccines. In conclusion, use of either of the single vaccines or the combination of MenBvac and MeNZB may have a considerable impact on the serogroup B meningococcal disease situation in many countries.
    Clinical and Vaccine Immunology 10/2007; 14(9):1062-9. · 2.60 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: 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.
    Clinical and Vaccine Immunology 08/2007; 14(7):830-8. · 2.60 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: To elucidate critical components of protective immune responses induced during the natural course of serogroup A meningococcal disease, we studied acute-, early-convalescent-, and late-convalescent-phase sera from Ethiopian patients during outbreaks in 2002 to 2003. Sera were obtained from laboratory-confirmed patients positive for serogroup A sequence type 7 (ST-7) meningococci (A:4/21:P1.20,9) (n = 71) and from Ethiopian controls (n = 113). The sera were analyzed using an enzyme-linked immunosorbent assay to measure levels of immunoglobulin G (IgG) against serogroup A polysaccharide (APS) and outer membrane vesicles (OMVs) and for serum bactericidal activity (SBA) using both rabbit and human complement sources. Despite relatively high SBA titers and high levels of IgG against APS and OMVs in acute-phase patient sera, significant increases were seen in the early convalescent phase. Antibody concentrations returned to acute-phase levels in the late convalescent phase. Considering all patients' sera, a significant but low correlation (r = 0.46) was observed between SBA with rabbit complement (rSBA) using an ST-5 reference strain and SBA with human complement (hSBA) using an ST-7 strain from Ethiopia. While rSBA demonstrated a significant linear relation with IgG against APS, hSBA demonstrated significant linear relationships with IgG against both APS and OMV. This study indicates that antibodies against both outer membrane proteins and APS may be important in providing the protection induced during disease, as measured by hSBA. Therefore, outer membrane proteins could also have a role as components of future meningococcal vaccines for the African meningitis belt.
    Clinical and Vaccine Immunology 05/2007; 14(4):451-63. · 2.60 Impact Factor
  • Vaccine 04/2007; 25(14):2537-8. · 3.49 Impact Factor
  • Einar Rosenqvist, Johan Holst, Hanne Nøkleby
    Vaccine 02/2007; 25(6):965-6. · 3.49 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: In southern Uganda, only sporadic cases of serogroup A meningococcal disease have been reported since 2000. As part of an immunogenicity study of the tetravalent meningococcal polysaccharide vaccine, nasopharyngeal swab samples were collected twice, 4 weeks apart, from 2-19-year-old healthy individuals in Mbarara, Uganda. Only 15 (2.0%) of the 750 individuals carried meningococci asymptomatically. Most of the strains were non-serogroupable and none were serogroup A. However, two individuals carried a serogroup W135 strain, sequence type (ST)-11, similar to the clone that was responsible for the epidemic in Burkina Faso in 2002. Our study further demonstrates the geographical spread of serogroup W135 ST-11 strain and thus the potential epidemic risk.
    Transactions of the Royal Society of Tropical Medicine and Hygiene 01/2007; 100(12):1159-63. · 1.82 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: To elucidate critical components of protective immune responses induced during the natural course of serogroup A meningococcal disease, we studied acute-, early-convalescent-, and late-convalescent-phase sera from Ethiopian patients during outbreaks in 2002 to 2003. Sera were obtained from laboratory-confirmed patients positive for serogroup A sequence type 7 (ST-7) meningococci (A:4/21:P1.20,9) (n = 71) and from Ethiopian controls (n = 113). The sera were analyzed using an enzyme-linked immunosorbent assay to measure levels of immunoglobulin G (IgG) against serogroup A polysaccharide (APS) and outer membrane vesicles (OMVs) and for serum bactericidal activity (SBA) using both rabbit and human complement sources. Despite relatively high SBA titers and high levels of IgG against APS and OMVs in acute-phase patient sera, significant increases were seen in the early convalescent phase. Antibody concentrations returned to acute-phase levels in the late convalescent phase. Considering all patients' sera, a significant but low correlation (r = 0.46) was observed between SBA with rabbit complement (rSBA) using an ST-5 reference strain and SBA with human complement (hSBA) using an ST-7 strain from Ethiopia. While rSBA demonstrated a significant linear relation with IgG against APS, hSBA demonstrated significant linear relationships with IgG against both APS and OMV. This study indicates that antibodies against both outer membrane proteins and APS may be important in providing the protection induced during disease, as measured by hSBA. Therefore, outer membrane proteins could also have a role as components of future meningococcal vaccines for the African meningitis belt.
    Clin Vaccine Immunol. 01/2007; 14(4):451-63.
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: MenBvac is an outer membrane vesicle vaccine against systemic meningococcal disease caused by serogroup B Neisseria meningitidis. In this placebo-controlled double-blind study including 374 healthy adolescents, the safety and immunogenicity of a schedule of three primary doses 6 weeks apart followed by a fourth dose a year later were evaluated. Antibody responses to the vaccine strain and heterologous strains (non-vaccine-type strains) and the persistence of these antibodies were measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay up to 1 year after the last dose. The proportion of subjects with SBA titers of > or = 4 against the vaccine strain increased from 3% prevaccination to 65% after the third dose. Ten months later, this proportion had declined to 28%. The fourth dose induced a booster response demonstrated by 93% of subjects achieving a titer of > or = 4. One year after the booster dose, 64% still showed SBA titers of > or = 4. Cross-reacting antibodies were induced against all heterologous strains tested, although the magnitude of SBA titers differed widely between the different strains. All four doses of MenBvac were safe. Both MenBvac and the placebo had reactogenicity profiles of mild to moderate local and systemic reactions. Pain, the most common reaction, was reported with similar frequencies in both groups. No serious adverse events occurred in the MenBvac group. This study confirmed the good immunogenicity of the primary course of MenBvac and demonstrated prolonged persistence and increased cross-reactivity of functional antibodies elicited by a booster dose.
    Clinical and Vaccine Immunology 07/2006; 13(7):790-6. · 2.60 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: The objectives of this study were to collect and characterize epidemic meningococcal isolates from Ethiopia from 2002 to 2003 and to compare them to 21 strains recovered during the previous large epidemic of 1988 to 1989. Ninety-five patients in all age groups with clinical signs of meningitis and a turbid cerebrospinal fluid (CSF) sample were included in the study of isolates from 2002 to 2003. Seventy-one patients (74.7%) were confirmed as having Neisseria meningitidis either by culture (n = 40) or by porA PCR (n = 31) of their CSF. The overall case fatality rate (CFR) was 11.6%; the N. meningitidis-specific CFR was 4.2%. All 40 strains were fully susceptible to all antibiotics tested except sulfonamide, were serotyped as A:4/21:P1.20,9, and belonged to sequence type 7 (ST-7). The strains from 1988 to 1989 were also equally susceptible and were characterized as A:4/21:P1.20,9, but they belonged to ST-5. Antigenic characterization of the strains revealed differences in the repertoire of lipooligosaccharides and Opa proteins between the old and the recent strains. PCR analysis of the nine lgt genes revealed the presence of the lgtAHFG genes in both old and recent strains; lgtB was present in only some of the strains, but no correlation with sequence type was observed. Further analysis showed that in addition to their pgm alleles, the Ethiopian ST-5 and ST-7 strains also differed in their tbpB, opa, fetA, and lgtA genes. The occurrence of new antigenic structures in strains sharing the same serogroup, PorA, and PorB may help explain the replacement of ST-5 by ST-7 in the African meningitis belt.
    Journal of Clinical Microbiology 04/2006; 44(3):861-71. · 4.07 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The "tailor-made" outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4-6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2,519 microg participants and in 87% of 50 microg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 microg dosage.
    Vaccine 03/2006; 24(9):1395-400. · 3.49 Impact Factor

Publication Stats

2k Citations
201 Downloads
241.56 Total Impact Points

Institutions

  • 2003–2012
    • Norwegian Institute of Public Health
      • • Division of Infectious Disease Control
      • • Department of Bacteriology and Immunology
      Kristiania (historical), Oslo County, Norway
  • 2006–2008
    • Armauer Hansen Research Institute
      Ādīs Ābeba, Ādīs Ābeba, Ethiopia
  • 2007
    • Environmental Science & Research
      Окленд, Auckland, New Zealand
  • 2004–2007
    • University of Oslo
      • • Department of Oral Biology
      • • Department of Biosciences
      Oslo, Oslo, Norway
  • 1997
    • Northern Institute For Cancer Research
      Newcastle-on-Tyne, England, United Kingdom