Use of cross-protection to identify novel vaccine candidates...

Chemistry: molecular biology and microbiology – Micro-organism – per se ; compositions thereof; proces of...

Reexamination Certificate

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C424S234100, C424S236100, C530S350000, C530S412000

Reexamination Certificate

active

07579182

ABSTRACT:
This invention discloses methods for identifyingFrancisella tularensisvaccine candidates. It enables identification of novel vaccine candidates and quality assurance for vaccine batches, assessment of protection in vaccinates and identification of the infecting agent in vaccinates. Mice were first vaccinated withBrucella abortusO-polysaccharide (OPS) vaccine. These animals were then given 10 LD50s ofF. tularensislive vaccine strain (LVS). Sixty percent (60%) of the vaccinated mice survived the multiple lethal doses. Sera were collected from these surviving mice and the antibodies were used to probe supernatant and cell lysates of liveF. tularensisLVS cultures. SeveralF. tularensiscomponents were identified only by the noted “survivor” antisera. Of these identified proteins, enzyme digestions and chemical oxidation suggest post-translational modifications of some proteins e.g. a 52 kDa glycoprotein, a 45 kDa lipoprotein and a 19 kDa nucleoprotein. The 52 kDa component caused nitrous oxide induction in tissue cultures at low concentrations, cell death at high concentrations. Vaccination with this gave partial protection while addition of other components acted synergistically to give enhanced protection from 250 LD50s ofF. tularensisLVS.

REFERENCES:
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Conlan et al, Mice vaccinated with the O-antigen ofFrancisella tularensisLVS lipopolysaccharide conjugated to bovine serum alburnin develop varying degrees of protective immunity against systemic or aerosol challenge with virulent type A and type B strains of the pathogen, Vaccine 20 (2002), pp. 3465-3471.
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