Evaluation of Highly Conserved Burkholderia pseudomallei Proteins as pan-Burkholderia Vaccine Antigen Candidates

Within the Burkholderia genus of Gram-negative bacteria exist two clades known to cause human disease: the B. pseudomallei complex and B. cepacia complex. Species of concern within the B. pseudomallei complex include B. mallei and the eponymous B. pseudomallei. Both are designated as Tier 1 Select Agents on account of their high intrinsic resistance to antibiotics, high mortality rate, and history of use as a biothreat agent. Numerous vaccine candidates to these B. pseudomallei complex species have been developed over the years, though none are currently approved for use in humans. On the other hand, the B. cepacia complex consists of >20 closely related species, many of which are opportunistic pathogens that predominantly infect individuals with weakened immunity or cystic fibrosis. While the B. cepacia complex similarly lacks adequate preventative options and harbors an innate resistance to many antibiotics, only a few groups have developed pre-clinical vaccines to these species. We and others have determined that there exist proteinaceous antigens that are highly conserved between both distinct clades of Burkholderia species, and interspecies cross-reactive immunity to these antigens has been described to a limited degree. This raises the possibility that a vaccine designed to protect against the B. pseudomallei complex may be capable of eliciting protection to B. cepacia complex species—a pan-Burkholderia vaccine. We have performed an in silico reverse vaccinology screen to scan the B. pseudomallei proteome for such highly conserved surface antigens and identified eight that matched our selection criteria. We recombinantly expressed three of these proteins (OmpA1, OmpA2, Pal) and attached them to a highly immunogenic gold nanoparticle vaccine delivery system that we have previously used in B. pseudomallei vaccine development. We first characterized the immune response elicited by these vaccines using splenocyte antigen recall assays and ELISAs, which identified IgA and IgG1/IgG2-balanced antibody responses paired with robust Th1 and Th17 cellular immunity. We also confirmed the ability of the OmpA1 and OmpA2 vaccines to protect mice from a lethal B. pseudomallei challenge. Finally, we measured the ability of vaccine-induced antibodies and splenic T cells to cross-react to more distantly related homologues from B. cepacia complex.

Name thesis:degree_name

Human Pathophysiology and Translational Medicine (Doctoral)

Grantor

The University of Texas Medical Branch at Galveston

Year dc:date.issued

2026

Author dc:creator

• Badten, Alexander Jesse 1995-

Committee members dc:contributor.committeemember

• Rytting, Erik
• McLellan, Susan L.F.
• Leitão, Jorge H.

Language dc:language.iso

English

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/12833

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/12833