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J Infect Dis. 2012 Oct 1;206(7):1050-8. doi: 10.1093/infdis/jis433. Epub 2012 Aug 14.

Hereditary hemochromatosis restores the virulence of plague vaccine strains.

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Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Lemont, University of Chicago, Illinois 60637, USA.


Nonpigmented Yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout (Hjv(-/-)) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis. Unlike wild-type mice, Hjv(-/-) mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv(-/-) mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines.

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