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. Itsendemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuatedvaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not providedcomplete protection. In this study, we constructed the select-agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccinestrain 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 SCIDgamma (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 challengewith the B. mallei lux (CSM001) wild-type strain.