A 52 Kilodalton Protein Vaccine Candidate for Francisella Tularensis

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Authors
  1. Sikora, C.A.
  2. Berger, B.J.
  3. Cherwonogrodzky, J.W.
Corporate Authors
Defence R&D Canada - Suffield, Ralston ALTA (CAN)
Abstract
For identifying Francisella tularensis vaccine candidates, mice were first vaccinated with Brucella abortus O-polysaccharide (OPS) vaccine. These animals were then given 10 LD50s of F. tularensis live vaccine strain (LVS). Sixty percent (60%) of the vaccinated mice survived the multiple lethal dose while all the unvaccinated control mice perished. Sera were collected from these surviving mice and used to probe supernatant and cell lysates of live F. tularensis LVS cultures. Several Francisella tularensis components were identified by this noted antiserum. Mouse serum from mice vaccinated with killed F. tularensis did not identify these components. Of these identified proteins, enzyme digestions and chemical oxidation suggest post-translational modifications for some of the proteins (e.g. a 52 kilodalton (kDa) glycoprotein, a 45 kDa lipoprotein and a 19 kDa nucleoprotein). In low concentrations, the 52 kDa component caused nitrous oxide induction in tissue cultures and in high concentrations it caused cell death. Vaccination with this protein gave mice partial protection (20% survival) from 250 LD50 of tularemia given intranasally while the addition of other components may have acted synergistically to give enhanced protection (i.e. 100% survival).

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Keywords
Francisella tularensis;tularemia;Brucella;brucellosis;vaccine;polysaccharide;protein;LD50;Surrogate marker;intranasal;mice;UNCLASSIFIED
Report Number
DRDC-SUFFIELD-TM-2004-074 — Technical Memorandum
Date of publication
01 Dec 2004
Number of Pages
40
DSTKIM No
CA025626
CANDIS No
523356
Format(s):
CD ROM

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