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  • The American Association of Immunologists  (2)
  • Dietrich, Jes  (2)
  • Mortensen, Rasmus  (2)
Medientyp
Verlag/Herausgeber
  • The American Association of Immunologists  (2)
Sprache
Erscheinungszeitraum
Fachgebiete(RVK)
  • 1
    Online-Ressource
    Online-Ressource
    The American Association of Immunologists ; 2016
    In:  The Journal of Immunology Vol. 196, No. 8 ( 2016-04-15), p. 3364-3374
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 196, No. 8 ( 2016-04-15), p. 3364-3374
    Kurzfassung: Cluster of virulence responder/sensor (CovR/S) mutant group A streptococci (GAS) are serious human pathogens of multiple M protein strains that upregulate expression of virulence factors, including the IL-8 protease Streptococcus pyogenes cell envelope proteinase (SpyCEP), thus blunting neutrophil-mediated killing and enabling ingress of bacteria from a superficial wound to deep tissue. We previously showed that a combination vaccine incorporating J8-DT (conserved peptide vaccine from the M protein) and a recombinant SpyCEP fragment protects against CovR/S mutants. To enhance the vaccine’s safety profile, we identified a minimal epitope (S2) that was the target for anti-SpyCEP Abs that could protect IL-8 from SpyCEP-mediated proteolysis. Abs from healthy humans and from mice experimentally infected with GAS also recognized S2, albeit at low titers. Native SpyCEP may be poorly immunogenic (cryptic or subdominant), and it would be to the organism’s advantage if the host did not induce a strong Ab response against it. However, S2 conjugated to diphtheria toxoid is highly immunogenic and induces Abs that recognize and neutralize SpyCEP. Hence, we describe a two-component peptide vaccine that induces Abs (anti-S2) that protect IL-8 from proteolysis and other Abs (anti-J8) that cause strain-independent killing in the presence of neutrophils. We show that either component alone is ineffectual in preventing skin infection and bacteremia due to CovR/S mutants but that the combination induces complete protection. This protection correlated with a significant influx of neutrophils to the infection site. The data strongly suggest that the lack of natural immunity to hypervirulent GAS strains in humans could be rectified by this combination vaccine.
    Materialart: Online-Ressource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: The American Association of Immunologists
    Publikationsdatum: 2016
    ZDB Id: 1475085-5
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 2
    Online-Ressource
    Online-Ressource
    The American Association of Immunologists ; 2015
    In:  The Journal of Immunology Vol. 195, No. 4 ( 2015-08-15), p. 1657-1664
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 195, No. 4 ( 2015-08-15), p. 1657-1664
    Kurzfassung: Each year, millions of people are infected with Streptococcus pyogenes, leading to an estimated 500,000 annual deaths worldwide. For unknown reasons, school-aged children have substantially higher infection rates than adults. The goal for this study was to provide, to our knowledge, the first detailed characterization of the human adaptive immune response against S. pyogenes in both children and adults. We report that all adults in our study, as well as most children, showed immunity against the two conserved group A streptococci (GAS) Ags, streptococcal C5a peptidase and immunogenic secreted protein. The response primarily consisted of three subsets of Th1 T cells, in which the TNF-α+ and IL-2+TNF-α+ subsets were most frequent. Humoral immunity was dominated by IgG1 and IgG3, whereas the Th2-associated IgG4 isotype was only detected at very low amounts. IgG3 levels correlated significantly with IFN-γ, but not with IL-5, IL-13, IL-17, or TNF-α. Interestingly, children showed a similar pattern of Ag-specific cytokine release, but displayed significantly lower levels of IgG3 and IFN-γ compared with adults. Thus, human immune responses against S. pyogenes consist of a robust Th1 cellular memory response in combination with IgG1/IgG3-dominated humoral immunity that increase with age. The significance of these data regarding both the increased GAS infection rate in children and the development of protective GAS vaccines is discussed.
    Materialart: Online-Ressource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: The American Association of Immunologists
    Publikationsdatum: 2015
    ZDB Id: 1475085-5
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
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