AUTHOR=Biryukov Sergei S. , Cote Christopher K. , Klimko Christopher P. , Dankmeyer Jennifer L. , Rill Nathaniel O. , Shoe Jennifer L. , Hunter Melissa , Shamsuddin Zain , Velez Ivan , Hedrick Zander M. , Rosario-Acevedo Raysa , Talyansky Yuli , Schmidt Lindsey K. , Orne Caitlyn E. , Fetterer David P. , Burtnick Mary N. , Brett Paul J. , Welkos Susan L. , DeShazer David 

TITLE=Evaluation of two different vaccine platforms for immunization against melioidosis and glanders

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.965518

DOI=10.3389/fmicb.2022.965518

ISSN=1664-302X

ABSTRACT=<p><italic>Burkholderia pseudomallei</italic> and the closely related species, <italic>Burkholderia mallei</italic>, produce similar multifaceted diseases which range from rapidly fatal to protracted and chronic, and are a major cause of mortality in endemic regions. Besides causing natural infections, both microbes are Tier 1 potential biothreat agents. Antibiotic treatment is prolonged with variable results, hence effective vaccines are urgently needed. The purpose of our studies was to compare candidate vaccines that target both melioidosis and glanders to identify the most efficacious one(s) and define residual requirements for their transition to the non-human primate aerosol model. Studies were conducted in the C57BL/6 mouse model to evaluate the humoral and cell-mediated immune response and protective efficacy of three <italic>Burkholderia</italic> vaccine candidates against lethal aerosol challenges with <italic>B. pseudomallei</italic> K96243, <italic>B. pseudomallei</italic> MSHR5855, and <italic>B. mallei</italic> FMH. The recombinant vaccines generated significant immune responses to the vaccine antigens, and the live attenuated vaccine generated a greater immune response to OPS and the whole bacterial cells. Regardless of the candidate vaccine evaluated, the protection of mice was associated with a dampened cytokine response within the lungs after exposure to aerosolized bacteria. Despite being delivered by two different platforms and generating distinct immune responses, two experimental vaccines, a capsule conjugate + Hcp1 subunit vaccine and the live <italic>B. pseudomallei</italic> 668 Δ<italic>ilvI</italic> strain, provided significant protection and were down-selected for further investigation and advanced development.</p>