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

Robert J Hogan,Eric R Lafontaine

doi:10.1128/msphere.00674-18

Abstract

Burkholderia pseudomallei and Burkholderia mallei are the causative agents of melioidosis and glanders, respectively. There is no vaccine to protect against these highly pathogenic bacteria, and there is concern regarding their emergence as global public health (B. pseudomallei) and biosecurity (B. mallei) threats. In this issue of mSphere, an article by Khakhum and colleagues (N. Khakhum, P. Bharaj, J. N. Myers, D. Tapia, et al., mSphere 4:e00570-18, 2019, https://doi.org/10.1128/mSphere.00570-18) describes a novel vaccination platform with excellent potential for cross-protection against both Burkholderia species. The report also highlights the importance of antibodies in immunity against these facultative intracellular organisms.

Highlights

Burkholderia pseudomallei and Burkholderia mallei are closely related bacteria causing fatal infections in humans and animals
Comparative analyses indicate that B. mallei evolved from B. pseudomallei through genomic reduction, and the genes retained by B. mallei have an average identity of 99% with B. pseudomallei orthologs [7,8,9,10]
Best-in-class vaccines afford increased survival against lethal challenge but do not prevent persistence of the organisms; mice develop lesions with high tissue burden and succumb to chronic infection despite possessing humoral and cellular immunity against B. pseudomallei and B. mallei. This failure to eliminate infection is a major obstacle in the field and emphasizes the need to expand the current pool of Burkholderia antigens for vaccine generation and to develop efficacious vaccination platforms

Summary

Introduction

Burkholderia pseudomallei and Burkholderia mallei are closely related bacteria causing fatal infections in humans and animals. The model produces hallmarks of melioidosis and glanders (low infectious and lethal doses, rapid bacterial replication in the lungs, dissemination to deep tissues, and formation of chronic lesions), and infected mice produce antibodies against antigens known to be targets of the human immune response, demonstrating immunological parallels [19,20,21,22,23,24,25,26].

Results

Conclusion