Hereditary hemochromatosis restores the virulence of plague vaccine strains.
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.
Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Lemont, University of Chicago, Illinois 60637, USA.
Lauriane E
LE
Quenee
Timothy M
TM
Hermanas
Nancy
N
Ciletti
Helene
H
Louvel
Nathan C
NC
Miller
Derek
D
Elli
Bill
B
Blaylock
Anthony
A
Mitchell
Jay
J
Schroeder
Thomas
T
Krausz
Joseph
J
Kanabrocki
Olaf
O
Schneewind
D000818:Animals; D005260:Female; D058851:GPI-Linked Proteins; D006432:Hemochromatosis / Q000150:complications* / Q000235:genetics; D000071020:Hemochromatosis Protein; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D050296:Microbial Viability; D010930:Plague / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage*; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D022223:Vaccines, Subunit / Q000008:administration & dosage; D014774:Virulence; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity*
D058851:GPI-Linked Proteins; C504414:HJV protein, mouse; D000071020:Hemochromatosis Protein; D008565:Membrane Proteins; D010931:Plague Vaccine; D014613:Vaccines, Attenuated; D022223:Vaccines, Subunit