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  • 1.
    Björkstén, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Diverse microbial exposure: Consequences for vaccine development2012In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 29, p. 4336-4340Article, review/survey (Refereed)
    Abstract [en]

    Numerous epidemiological studies suggest that there is an inverse relationship between "immunologically mediated diseases of affluence", such as allergy, diabetes and inflammatory bowel disease on one hand and few infections encountered in early childhood, on the other hand. Careful analysis of the epidemiological, clinical and animal studies taken together, however, suggests that the protection is mediated by broad exposure to a wealth of commensal, non-pathogenic microorganisms early in life, rather than by infections. Microbial exposure has little relationship with "hygiene" in the usual meaning of the word and the term "hygiene hypothesis" is therefore misleading. A better term would be "microbial deprivation hypothesis". The suggestion that childhood infections would protect against allergic disease led to unfortunate speculations that vaccinations would increase the risk for allergies and diabetes. Numerous epidemiological studies have therefore been conducted, searching for a possible relationship between various childhood vaccinations on one hand and allergy on the other hand. It is reasonable from these studies to conclude that vaccinations against infectious agents neither significantly increase, nor reduce the likelihood of immunologically mediated diseases. It is established that the postnatal maturation of immune regulation is largely driven by exposure to microbes. Germ free animals manifest excessive immune responses when immunised and they do not develop normal immune regulatory function. The gut is by far the largest source of microbial exposure, as the human gut microbiome contains up to 1014 bacteria, i.e. ten times the number of cells in the human body. Several studies in recent years have shown differences in the composition of the gut microbiota between allergic and non-allergic individuals and between infants living in countries with a low and a high prevalence of immune mediated diseases. The administration of probiotic bacteria to pregnant mothers and postnatal to their infants has immune modulatory effects. So far, however, probiotic bacteria do not seem to significantly enhance immune responses to vaccines. The potential to improve vaccine responses by modifying the gut microbiota in infants and the possibility to employ probiotic bacteria as adjuvants and/or delivery vehicles, is currently explored in several laboratories. Although to date few clinical results have been reported, experimental studies have shown some encouraging results.

  • 2. Iriemenam, Nnaemeka C.
    et al.
    Khirelsied, Atif H.
    Nasr, Amre
    ElGhazali, Gehad
    Giha, Haider A.
    Elhassan A-Elgadir, Thoraya M.
    Agab-Aldour, Ahmed A.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Anders, Robin F.
    Theisen, Michael
    Troye-Blomberg, Marita
    Elbashir, Mustafa I.
    Berzins, Klavs
    Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan2009In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 1, p. 62-71Article in journal (Refereed)
    Abstract [en]

    Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children <5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in >5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses.

  • 3.
    Jacobsson, Susanne
    et al.
    Örebro University, School of Health and Medical Sciences.
    Hedberg, Sara Thulin
    Mölling, Paula
    Unemo, Magnus
    Comanducci, Maurizio
    Rappuoli, Rino
    Olcén, Per
    Prevalence and sequence variations of the genes encoding the five antigens included in the novel 5CVMB vaccine covering group B meningococcal disease2009In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 10, p. 1579-1584Article in journal (Refereed)
    Abstract [en]

    During the recent years, projects are in progress for designing broad-range non-capsular-based meningococcal vaccines, covering also serogroup B isolates. We have examined three genes encoding antigens (NadA, GNA1030 and GNA2091) included in a novel vaccine, i.e. the 5 Component Vaccine against Meningococcus B (5CVMB), in terms of gene prevalence and sequence variations. These data were combined with the results from a similar study, examining the two additional antigens included in the 5CVMB (fHbp and GNA2132).

    nadA and fHbp v. 1 were present in 38% (n=36), respectively 71% (n=67) of the isolates, whereas gna2132, gna1030 and gna2091 were present in all the Neisseria meningitidis isolates tested (n=95). The level of amino acid conservation was relatively high in GNA1030 (93%), GNA2091 (92%), and within the main variants of NadA and fHbp. GNA2132 (54% of the amino acids conserved) appeared to be the most diversified antigen. Consequently, the theoretical coverage of the 5CVMB antigens and the feasibility to use these in a broad-range meningococcal vaccine is appealing.

  • 4.
    Jacobsson, Susanne
    et al.
    Örebro University, School of Health and Medical Sciences.
    Mölling, Paula
    Örebro University, Örebro, Sweden.
    Olcén, Per
    Seroprevalence of antibodies against fHbp and NadA, two potential vaccine antigens for Neisseria meningitidis2009In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 42, p. 5755-5759Article in journal (Refereed)
    Abstract [en]

    The IgG antibody levels directed against fHbp and NadA, two potential vaccine antigens for Neisseria meningitidis, were examined in order to investigate the extent of natural immunisation against these antigens in different age groups. As a comparison, the IgG antibody levels against Haemophilus influenzae type b were examined. In the two youngest age groups, below 10 years of age, relatively low levels of both anti-fHbp and anti-NadA were measured. A 15-fold higher geometric mean concentration of anti-fHbp was noted in the age group 20-29 years as compared to the age group 15-19 years. The peak concentration was found at 30-39 years, followed by decreased levels with age. Anti-NadA showed a certain increase up to 9 years followed by an even increase up to 40-49 years.

  • 5.
    Jacobsson, Susanne
    et al.
    Örebro University, Department of Clinical Medicine.
    Thulin, Sara
    Mölling, Paula
    Unemo, Magnus
    Comanducci, Maurizio
    Rappuoli, Rino
    Olcén, Per
    Sequence constancies and variations in genes encoding three new meningococcal vaccine candidate antigens2006In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 24, no 12, p. 2161-2168Article in journal (Refereed)
    Abstract [en]

    By the strategy “reverse vaccinology” a number of new antigens have been identified in Neisseria meningitidis, which are potential candidates for a highly needed broad-spectrum meningococcal vaccine. In the present study we examined the prevalence, sequence constancies and variations of the genes encoding three of these new antigens designated, genome-derived neisserial antigen (GNA) 1870, GNA1946 and GNA2132. All three genes were present in all     N. meningitidis isolates tested. Concerning gna1870, three major variants of the gene sequences and deduced amino acid sequences were identified and 56% of the deduced amino acids were conserved in all isolates. In gna1946, 98% of the deduced amino acids were conserved and in gna2132, 54% of the deduced amino acids were conserved. Based on gene prevalence and conservation, all three antigens are promising candidates for an effective meningococcal vaccine against all N. meningitidis irrespective of serogroup.

  • 6.
    Lindh, Ingrid
    et al.
    Örebro University, School of Science and Technology. Örebro Life Sci Ctr, Univ Örebro, Örebro, Sweden; Sch Sci & Technol, Univ Örebro, Örebro, Sweden.
    Bråve, Andreas
    Swedish Institute for Communicable Disease Control (SMI), Stockholm, Sweden.
    Hallengärd, David
    Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Hadad, Ronza
    Örebro University, School of Science and Technology. Örebro Life Sci Ctr, Univ Örebro, Örebro, Sweden.
    Kalbina, Irina
    Örebro University, School of Science and Technology. Örebro Life Sci Ctr, Univ Örebro, Örebro, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology. Örebro Life Sci Ctr, Univ Örebro, Örebro, Sweden.
    Andersson, Sören
    Örebro University Hospital. Örebro Life Sci Ctr, Univ Örebro, Örebro, Sweden; Örebro University Hospital, Örebro, Sweden.
    Oral delivery of plant-derived HIV-1 p24 antigen in low doses shows a superior priming effect in mice compared to high doses2014In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 32, no 20, p. 2288-2293Article in journal (Refereed)
    Abstract [en]

    During early infection with human immunodeficiency virus type 1 (HIV-1), there is a rapid depletion of CD4+ T-cells in the gut-associated lymphoid tissue (GALT) in the gastrointestinal tract. Therefore, immediate protection at these surfaces is of high priority for the development of an HIV-1 vaccine. Thus, transgenic plants expressing HIV-1 antigens, which are exposed to immune competent cells in the GALT during oral administration, can be interesting as potential vaccine candidates. In the present study, we used two HIV-1 p24 antigen-expressing transgenic plant systems, Arabidopsis thaliana and Daucus carota, in oral immunization experiments. Both transgenic plant systems showed a priming effect in mice and induced humoral immune responses, which could be detected as anti-p24-specific IgG in sera after an intramuscular p24 protein boost. Dose-dependent antigen analyses using transgenic Arabidopsis thaliana indicated that low p24 antigen doses were superior to high p24 antigen doses

  • 7. Silfverdal, S. A.
    et al.
    Ehlin, A.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Protection against clinical pertussis induced by whole-cell pertussis vaccination is related to primo-immunisation intervals2007In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 25, no 43, p. 7510-7515Article in journal (Refereed)
    Abstract [en]

    AIMS: Information on subjects who had at least three immunisations against pertussis was provided by longitudinal data from the 1970 British Cohort Study (BCS70) and used to assess whether three whole-cell pertussis (wP) immunisations given within less than 5 months confer less effective protection in childhood compared with a schedule with a longer interval.

    METHODS: Age at pertussis infection was the dependent variable in a Cox regression analysis, to investigate associations with duration between first and third pertussis immunisation; with third immunisation modelled as a time-dependent covariate. Adjustment was for number of pertussis immunisations (three or four), sex, social class and other potential confounding factors.

    RESULTS: A total of 8545 children were included in the analysis and 556 had a history of whooping cough. A duration of over 4 months between first and third pertussis immunisations is statistically significantly associated with a reduced risk of pertussis infection by age 10 years, compared with three immunisations given over a shorter period, producing a statistically significant adjusted hazard ratio of 0.74 (0.62-0.92). A fourth immunisation against pertussis further enhanced the protective effect with a hazard ratio of 0.59 (0.44-0.82).

    CONCLUSION: These results were based on a historical UK cohort using wP vaccine, and indicate that a vaccination schedule with an interval between the immunisations greater than 4 months, and also including a fourth immunisation, would be more effective in this population than a three dose schedule within a shorter interval without booster.

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