Abstract:
:Francisella tularensis is the intracellular bacterial pathogen causing the respiratory life-threatening disease tularemia. Development of tularemia vaccines has been hampered by an incomplete understanding of the correlates of immunity. Moreover, the importance of lung cellular immunity in vaccine-mediated protection against tularemia is a controversial matter. Live attenuated vaccine strains of F. tularensis such as LVS (Live Vaccine Strain), elicit an immune response protecting mice against subsequent challenge with the virulent SchuS4 strain, yet the protective immunity against pulmonary challenge is limited in its efficacy and longevity. We established a murine intra-nasal immunization model which distinguishes between animals fully protected, challenged at 4 weeks post double-vaccination (200 inhalation Lethal Dose 50%, LD50, of SchuS4), and those which do not survive the lethal SchuS4 infection, challenged at 8 weeks post double vaccination. Early in the recall immune response in the lung (before day 3), disease progression and bacterial dissemination differed considerably between protected and non-protected immunized mice. Pre-challenge analysis, revealed that protected mice, exhibited significantly higher numbers of lung Ft-specific memory T cells compared to non-protected mice. Quantitative PCR analysis established that a higher magnitude, lung T cells response was activated in the lungs of the protected mice already at 24 h post-challenge. The data imply that an early memory response within the lung is strongly associated with protection against the lethal SchuS4 bacteria presumably by restricting the dissemination of the bacteria to internal organs. Thus, future prophylactic strategies to countermeasure F. tularensis infection may require modulation of the immune response within the lung.
journal_name
Vaccinejournal_title
Vaccineauthors
Bar-On L,Cohen H,Elia U,Rotem S,Bercovich-Kinori A,Bar-Haim E,Chitlaru T,Cohen Odoi
10.1016/j.vaccine.2017.10.053subject
Has Abstractpub_date
2017-12-15 00:00:00pages
7001-7009issue
50eissn
0264-410Xissn
1873-2518pii
S0264-410X(17)31461-5journal_volume
35pub_type
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