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

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DOIResolve DOI: http://doi.org/10.1016/j.molimm.2012.10.043
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TypeArticle
Journal titleMolecular Immunology
ISSN0161-5890
Volume54
Issue1
Pages5867; # of pages: 10
Subjectcytokine; francisella tularensis vaccine; gamma interferon; live vaccine; monocyte chemotactic protein 1; tumor necrosis factor alpha; unclassified drug; animal cell; animal experiment; animal model; animal tissue; antibody response; article; bacterial immunity; bacterial strain; drug mechanism; female; Francisella tularensis; gene deletion; immune response; immunization; mouse; nonhuman; nucleotide sequence; priority journal; Administration, Cutaneous; Administration, Inhalation; Animals; Bacterial Vaccines; Female; Francisella tularensis; Gene Deletion; Immunity; Immunity, Innate; Mice; Mice, Inbred BALB C; Organisms, Genetically Modified; Tularemia; Vaccination; Virulence; Bacteria (microorganisms); Francisella; Francisella tularensis; Mus
AbstractFrancisella 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. © 2012.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC)
Peer reviewedYes
NPARC number21270716
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Record identifier61b90b2b-f56e-46c2-8fda-451932b3cf03
Record created2014-02-17
Record modified2016-05-09
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