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  • 1
    ISSN: 1432-1076
    Keywords: Key wordsHaemophilus influenzae type b ; Acellular pertussis ; Vaccination ; PRP-tetanus ; Diphtheria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract With an increasing number of new vaccines available for routine childhood immunization, combination vaccines are needed in order to maintain or achieve a high compliance with recommended immunization programmes. In a prospective, randomized, comparative, multi-centre study, 822 healthy infants were enrolled to receive three doses of either a candidate or a commercially available Haemophilus influenzae type b (Hib) vaccine concomitantly with diphtheria-, tetanus- acellular pertussis (DTaP) vaccine. Study subjects were randomly allocated to one of the following groups: (1) separate, or (2) mixed injection of DTaP and candidate Hib vaccine, or (3) separate injection of DTaP and commercial Hib vaccine. One year later the first 189 study subjects received either separate or mixed injections of the same Hib and DTaP vaccines as booster doses. Evaluation of reactogenicity was based on diary cards completed by parents. Immunogenicity was documented by measuring IgG antibody concentrations in serum samples taken before and 4 weeks after primary and booster vaccination. No serious adverse events occurred and most local and systemic reactions were mild to moderate. Booster doses were more reactogenic than primary doses with all groups. Antibody concentrations against pertussis antigens were similar to those seen with DTaP alone. All but one subject had protective antibody concentrations against diphtheria and tetanus. Primary immune response to the Hib vaccine was significantly lower in the group receiving the mixed Hib-DTaP vaccine, however, ≥95% of vaccinees had anti-Hib antibody concentrations ≥0.15 μg/ml and there was a marked booster response (〉100-fold) in all groups. Conclusions Mixing DTaP and Hib vaccines for primary immunization caused a decrease in anti-Hib antibody response, although after primary immunization as after booster doses, all subjects showed antibody concentrations considered to be protective for invasive Hib disease. Mixing of the vaccines did not result in increased reactogenicity.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1076
    Keywords: Key words Haemophilus influenzae type b  ;   Combination vaccine  ;  Immunological memory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The lack of an adequate immune response to the major polysaccharide of the Haemophilus influenzae type b (Hib) capsule (polyribosyl ribitol phosphate) (PRP) in very young infants (〈 18 months) can be overcome by conjugating PRP to a T-cell dependent carrier protein. We studied whether administration of a tetanus-PRP conjugate vaccine reconstituted with a diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine as a three dose primary course at 3, 4 and 5 months of age induced PRP-specific immunological memory, by examining the anti-PRP response to a dose of unconjugated PRP given with the DTPa-HBV booster approximately 1 year later. The unconjugated PRP elicited protective anti-PRP antibody levels (≥ 0.15 μg/ml) in all but 3 of the 369 vaccinees, including 13 infants who failed to demonstrate a measurable immune response after the primary course. In a sub-cohort of 54 subjects all had anti-PRP levels ≥ 0.5 μg/ml within 7–14 days of the booster showing a rapid anamnestic type response. Both primary and booster responses were predominantly IgG1 indicating a T-cell dependent response. The DTPa-HBV components elicited protective anti-diphtheria, anti-tetanus and anti-HBs antibody levels in ≥ 98.5% of vaccinees, and immune responses to each of the acellular pertussis vaccine components in 92.3%–97.3% of subjects. Conclusion The tetanus-PRP conjugate vaccine not only elicited a good primary humoral response, but also induced immunological memory so that the infants were able to mount a large and rapid immune response to subsequent exposure to plain PRP, indicating that protection against circulating wild-type Hib had been generated. Successful induction of immunological memory occurred even when there was no measurable humoral anti-PRP response to the primary course. Tetanus-PRP conjugate vaccine can be used in combination with DTPa-HBV vaccine, when administered separately or as a single injection in the same syringe, in primary immunisation schedules at 3, 4 and 5 months of age.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-3023
    Keywords: Key words: Bacterial adherence; Intraepithelial calcium flux; Mucosal host defense; PgE2 release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Mucosal epithelial cells contribute significantly to host defense mechanisms. Uroepithelial cells (UEC) from healthy donors suppress bacterial growth in vitro. Bacterial adherence to UEC has been shown to be a prerequisite. Similar results have been shown for buccal epithelial cells (BEC). The host response triggered by the host–parasite interaction seems to involve signal transduction and intracellular activation of second messengers. In this study the intraepithelial calcium flux was analyzed in individual BEC after bacterial contact. BEC were derived from scrapes of the buccal mucosa and labelled with fluo-3 (a calcium indicator). Thereafter the cells were analyzed immediately with a FACscan flowcytometer. The intracellular events were evaluated before and after the addition of viable E. coli bacteria (strain 4389, K1O1H7, pili II pos.). For control, the influence of prostaglandins, histamine, PMA, LPS and opsonized avital E. coli on the epithelial calcium flux was investigated. Additionally, supernatants of BEC-E. coli cocultures were analyzed with respect to their PgE2 content. PgE2 concentrations in supernatants of BEC, cultured alone or together with E. coli, were measured by a commercial PgE2 ELISA kit. The addition of vital E. coli to BEC was promptly answered by a significant intracellular calcium flux. PgE2, histamine and PMA, but not PgF2α, PgE1, LPS and opsonized E. coli, increased intracellular calcium. BEC alone did not release PgE2. After coculture with E. coli increased levels of PgE2 were measured in the supernatants. PgE2 release was still enhanced by coactivation of the BEC with phorbolester (PMA). Our results confirm that calcium flux in mucosal epithelial cells is stimulated by the cell–bacteria contact. We suggest that the increased PgE2 release amplifies the stimulation of intraepithelial second messengers. The resulting cell activation may lead to the secretion of antimicrobial peptides, thereby contributing to the regulation of mucosal host resistance to bacterial infections.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Monatsschrift Kinderheilkunde 146 (1998), S. 304-308 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Hämophilus influenzae ; Bakterielle Adhärenz ; Mukosa-Epithelzelle ; H.I.-Impfung ; Key wordsHaemophilus influenzae ; Bacterial adherence ; Mucosal epithelial cell ; H.I.-vaccine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The following overview describes the conditions of the host-parasite relationship which are important for the infection with Haemophilus influenzae (H.I.). New epidemiological data point out that the general vaccination of infants and children with the HIB-conjugate vaccine has been followed by a shift from encapsulated H.I. type B to unencapsulated, low-virulent strains. However, unencapsulated H.I. strains have been cultured increasingly from blood samples of patients with severe septicemic infections. Elderly patients with underlying chronic lung disease as well as children are affected. It is well accepted that in the pathogenesis of H.I.-infection bacterial adherence to mucosal epithelial cells of the oropharynx precedes colonization. However, bacterial pili as special virulence factors that promote binding to epithelial cell receptors (=bacterial adherence) have been especially demonstrated in vitro on the low virulent, unencapsulated H.I.-strains and are lacking on most in vitro grown encapsulated strains. Nevertheless, unencapsulated strains were taken from oropharyngeal swaps while encapsulated strains originated from blood and/or cerebrospinal fluid. The published controversial data on the adhesive capacity of H.I.B./H.I. as a virulence property are discussed. We propose to analyze systematically the host-parasite interaction with unencapsulated H.I.-strains in order to protect patients at risk from infections with these bacteria showing increasing clinical virulence. It would be desireable to develop H.I.B./H.I. vaccines that contain ”common” antigens of unencapsulated H.I.-strains in addition to the type B-capsular antigens.
    Notes: Zusammenfassung Nach Einführung der Konjugatimpfung gegenüber Typ-B-kapseltragenden Hämophilus-influenzae-Bakterien wurde im Kindesalter eine Verschiebung des Erregerspektrums zu nicht-kapseltragenden Erregern beobachtet. Allerdings werden zunehmend nicht-kapseltragende Erreger auch bei Hämophiluserkrankungen mit septischem Verlauf kulturell nachgewiesen. Auch ältere Risikopatienten mit chronischen Lungenerkrankungen weisen ein erhöhtes Risiko auf, septische Hämophilusinfektionen zu erleiden, wobei Virulenzfaktoren wie Typ-B-Kapselbildung nur in der Hälfte der Fälle eine Rolle spielen. Für die Pathogenese der Hämophilusinfektion wird eine bakterielle Adhärenz an Oropharyngealepithelien als Voraussetzung der Kolonisierung postuliert. Adhäsine (bakterielle Pili mit Bindungsstellen für Epithelrezeptoren) lassen sich in vitro in aller Regel v.a. bei unbekapselten, im klinischen Alltag als weniger virulent geltenden Hämophilusstämmen nachweisen. Allerdings stimmen die Entnahmeorte von unbekapselten (zumeist Oropharyngealabstriche) und kapseltragenden Erregern (zumeist Blut- bzw. Liquorkultur) nicht überein. So wird nach kritischer Wertung der Literaturdaten aus experimentellen Untersuchungen diskutiert, wie sich die kontroversen Befunde bezüglich der Hämophilusadhärenz an der Wirtszelle im Zusammenhang mit der Erregervirulenz erklären lassen. Als Ausblick erscheint es wesentlich, die Erreger-Wirts-Beziehung der unbekapselten, als weniger virulent geltenden Erreger systematisch zu untersuchen, um Risikopatienten zukünftig auch gegenüber diesen klinisch zunehmend virulenteren Erregern zu schützen. Es wäre wünschenswert, daß zukünftige Impfstoffe neben den Immunisierungskomponenten gegenüber Typ-B-Kapselantigenen zusätzliche Bakterienantigene, die sich bei den ursprünglich als weniger virulent geltenden Erregerstämmen finden, enthielten.
    Type of Medium: Electronic Resource
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