Nejvíce citovaný článek - PubMed ID 11895957
Francisella tularensis subspecies tularensis is a highly virulent intracellular bacterial pathogen, causing the disease tularemia. However, a safe and effective vaccine for routine application against F. tularensis has not yet been developed. We have recently constructed the deletion mutants for the DsbA homolog protein (ΔdsbA/FSC200) and a hypothetical protein IglH (ΔiglH/FSC200) in the type B F. tularensis subsp. holarctica FSC200 strain, which exerted different protection capacity against parental virulent strain. In this study, we further investigated the immunological correlates for these different levels of protection provided by ΔdsbA/FSC200 and ΔiglH/FSC200 mutants. Our results show that ΔdsbA/FSC200 mutant, but not ΔiglH/FSC200 mutant, induces an early innate inflammatory response leading to strong Th1-like antibody response. Furthermore, vaccination with ΔdsbA/FSC200 mutant, but not with ΔiglH/FSC200, elicited protection against the subsequent challenge with type A SCHU S4 strain in mice. An immunoproteomic approach was used to map a spectrum of antigens targeted by Th1-like specific antibodies, and more than 80 bacterial antigens, including novel ones, were identified. Comparison of tularemic antigens recognized by the ΔdsbA/FSC200 post-vaccination and the SCHU S4 post-challenge sera then revealed the existence of 22 novel SCHU S4 specific antibody clones.
- Klíčová slova
- antibody response, cytokines, immunoproteomics, protection, tularemia,
- MeSH
- atenuované vakcíny aplikace a dávkování genetika imunologie MeSH
- bakteriální vakcíny aplikace a dávkování genetika imunologie MeSH
- cytokiny metabolismus MeSH
- faktory virulence nedostatek MeSH
- Francisella tularensis klasifikace enzymologie imunologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- proteindisulfidisomerasy nedostatek MeSH
- Th1 buňky imunologie MeSH
- tularemie imunologie prevence a kontrola MeSH
- tvorba protilátek * MeSH
- zkřížená ochrana * MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- atenuované vakcíny MeSH
- bakteriální vakcíny MeSH
- cytokiny MeSH
- faktory virulence MeSH
- proteindisulfidisomerasy MeSH