Burkholderia pseudomallei Δ tonB Δ hcp1 Live Attenuated Vaccine Strain Elicits Full Protective Immunity against Aerosolized Melioidosis Infection

Abstract

In recent years, an increasing number of melioidosis cases have been reported in several regions where melioidosis is endemic and in areas where melioidosis had not commonly been diagnosed. Currently, the estimated burden of disease is around 165,000 new cases annually, including 89,000 cases that have fatal outcomes. This life-threatening infectious disease is caused by B. pseudomallei, which is classified as a Tier 1 select agent. Due to the high case fatality rate, intrinsic resistance to multiple antibiotic treatments, susceptibility to infection via the aerosol route, and potential use as a bioweapon, we have developed an effective live attenuated PBK001 vaccine capable of protecting against aerosolized melioidosis.

Role of Recipient Susceptibility Factors During Contact-Dependent Interbacterial Competition

“…Understanding the mode of action of antibacterial toxins and their target spectra may help us develop novel antibacterial therapies in biomedical and agricultural applications (Sana et al, 2017;Bernal et al, 2018;Trunk et al, 2018;Khakhum et al, 2019;Allsopp et al, 2020). For example, accumulating evidence indicated that T6SSs in commensal bacteria such as Bacteroides fragilis and Pseudomonas protegens play a critical role in the defense against invading bacterial pathogens and impact microbial community in the gut of mammalian and insect, respectively (Chatzidaki-Livanis et al, 2016;Wexler et al, 2016;Vacheron et al, 2019).…”

“…Based on the current knowledge, we proposed three strategies for defense against pathogens in a polymicrobial community (Figure 6). One conventional way is engineering strains with specific or arrays of various immunity genes that may offer broad-spectrum protection (Sana et al, 2017;Trunk et al, 2018;Khakhum et al, 2019). With the understanding of the RS factors, alternative approaches could be designed in these commensal bacteria with better survival and competitive capacity.…”

Novel multi-component vaccine approaches for Burkholderia pseudomallei

“…Immunization of C57BL/6 mice with Bp82 conferred 100% survival over 60 days against pulmonary melioidosis [64]. In a recent study, immunization of C57Bl/6 mice with a B. pseudomallei strain lacking tonB and hcp1 also provided complete protection against an otherwise lethal aerosol challenge [67]. Vaccination of mice with the ΔrelA ΔspoT mutant resulted in full protection against infection with wild-type B. pseudomallei [65].…”

“…An asd mutant of B. pseudomallei 1026b was avirulent in BALB/c mice, and animals vaccinated with the mutant were protected against acute inhalation melioidosis [66]. In a recent study, immunization of C57Bl/6 mice with a B. pseudomallei strain lacking tonB and hcp1 also provided complete protection against an otherwise lethal aerosol challenge [67]. Immunization with VACCINES FOR EMERGING PATHOGENS: FROM RESEARCH TO THE CLINIC.…”

Antibodies Are Major Drivers of Protection against Lethal Aerosol Infection with Highly Pathogenic Burkholderia spp

“…In this issue of mSphere , a study by Khakhum and colleagues (30) demonstrates that immunization of C57BL/6 mice with a novel B. pseudomallei live attenuated strain (LAS) results in remarkable protection against lethal aerosol challenge with homologous wild-type bacteria. Khakhum et al show that LAS vaccination elicits robust humoral and cellular immune responses, provides 100% survival for a period of up to 27 days after infection with highly pathogenic B. pseudomallei strain K96243, and results in outstanding rates of bacterial clearance in the lungs, liver, and spleen (71%).…”