کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5917366 1163785 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Correlates of protection following vaccination of mice with gene deletion mutants of Francisella tularensis subspecies tularensis strain, SCHU S4 that elicit varying degrees of immunity to systemic and respiratory challenge with wild-type bacteria
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Correlates of protection following vaccination of mice with gene deletion mutants of Francisella tularensis subspecies tularensis strain, SCHU S4 that elicit varying degrees of immunity to systemic and respiratory challenge with wild-type bacteria
چکیده انگلیسی

Francisella tularensis subspecies tularensis is an extremely virulent facultative intracellular bacterial pathogen capable of causing significant mortality in humans when inhaled. Consequently, subspecies tularensis was developed as a biological weapon more than 50 years ago. To counter this threat the US Army empirically developed a live vaccine strain, F. tularensis LVS, from the less virulent holarctica subspecies. In human experiments LVS afforded substantial protection against transdermal challenge with clinical subspecies tularensis strain, SCHU S4, but lesser protection against infection initiated by inhalation of the pathogen. Several regulatory and clinical issues remain unresolved for this vaccine, including the absence of a robust correlate of protection. To try to address this, we have developed several defined gene deletion mutants of SCHU S4 that elicit varying degrees of protection in a mouse dermal or respiratory challenge model. In the present study, we have examined whether host immune responses to immunization with such live vaccine candidates can serve as correlates of protection. Antibody responses were unable to distinguish between effective and ineffective vaccine strains. However, several cytokine responses to vaccination showed some promise. Especially, serum levels of TNFα, IFNγ, and MCP-1 between days 4 and 7 after vaccination appear to correlate with protection against respiratory challenge.

► Comprehensive comparison of immune responses to effective and ineffective mutant vaccine strains of F. tularensis. ► Correlates of protection observed in serum and splenic cytokine and chemokine responses. ► Vaccine strain persistence correlates with protection.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 54, Issue 1, May 2013, Pages 58-67
نویسندگان
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