Burkholderia pseudomallei Complex Subunit and Glycoconjugate Vaccines and Their Potential to Elicit Cross-Protection to Burkholderia cepacia Complex

Abstract

Burkholderia are a group of Gram-negative bacteria that can cause a variety of diseases in at-risk populations. B. pseudomallei and B. mallei, the etiological agents of melioidosis and glanders, respectively, are the two clinically relevant members of the B. pseudomallei complex (Bpc). The development of vaccines against Bpc species has been accelerated in recent years, resulting in numerous promising subunits and glycoconjugate vaccines incorporating a variety of antigens. However, a second group of pathogenic Burkholderia species exists known as the Burkholderia cepacia complex (Bcc), a group of opportunistic bacteria which tend to affect individuals with weakened immunity or cystic fibrosis. To date, there have been few attempts to develop vaccines to Bcc species. Therefore, the primary goal of this review is to provide a broad overview of the various subunit antigens that have been tested in Bpc species, their protective efficacy, study limitations, and known or suspected mechanisms of protection. Then, we assess the reviewed Bpc antigens for their amino acid sequence conservation to homologous proteins found in Bcc species. We propose that protective Bpc antigens with a high degree of Bpc-to-Bcc sequence conservation could serve as components of a pan-Burkholderia vaccine capable of protecting against both disease-causing groups.

Keywords: Burkholderia cepacia complex; Burkholderia mallei; Burkholderia pseudomallei; cystic fibrosis; glanders; glycoconjugate; melioidosis; subunit; vaccines.

Figure 1

Breakdown of the Bcc isolates used in the BLAST screen for Bcc-to-B. pseudomallei antigen sequence conservation based on (a) species, (b) continent of origin, and (c) isolation source. Graphs were created using Graphpad Prism 10.

Figure 2

ChimeraX v1.6.1-generated ribbon structures of β-barrel antigens with a high degree of Bcc-to-B. pseudomallei amino acid sequence identity [170]. Residues not predicted using DeepTMHMM v1.0.24 to be extracellularly oriented are colored in translucent gray [171]. Extracellularly oriented residues that are 100% conserved between the Bcc homologs and the B. pseudomallei K96243 reference are colored light gray. Residues which are substituted or missing in Bcc homologs are colored according to the scale bar to represent the degree of sequence conservation (identity). (a,b) Front and back views of the BamA extracellular loops (AFDB accession AF-Q63T20-F1) [172]. (c,d) Front and back views of the OmpW1 extracellular loops (AFDB accession AF-Q63UP4-F1) [172].

Figure 3

ChimeraX v1.6.1-generated surface structures of OmpA domain-containing antigens [170]. Residues that are 100% conserved between the Bcc homologs and the B. pseudomallei K96243 reference are colored light gray. Residues which are substituted or missing in Bcc homologs are colored according to the scale bar to represent the degree of sequence conservation (identity). (a,b) Front and back views of Omp7 (AFDB accession AF-Q63RA7-F1) [172]. (c,d) Front and back views of Omp1 (AFDB accession AF-Q63W89-F1) [172]. (e,f) Front and back views of Omp3 (AFDB accession AF-Q63RZ9-F1) [172]. The OmpA domain, which is the most likely region to be targetable by antibodies, is the globular domain in the upper half of each panel.