Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders.
Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. mallei lux (CSM001) wild-type strain.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Christopher L
CL
Hatcher
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Tiffany M
TM
Mott
Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas, USA.
Laura A
LA
Muruato
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Elena
E
Sbrana
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA Institute for Translational Sciences, University of Texas Medical Branch, Galveston, Texas, USA Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA altorres@utmb.edu.
Alfredo G
AG
Torres
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D042726:Burkholderia mallei / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005896:Glanders / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D007114:Immunization; D007117:Immunization, Secondary; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D009154:Mutation; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated