# Antibodies to Burkholderia pseudomallei Outer Membrane Proteins Coupled to Nanovaccines Exhibit Cross-Reactivity to B. cepacia Complex and Pseudomonas aeruginosa Homologues

## TL;DR

This study explores how antibodies from a B. pseudomallei nanovaccine can cross-react with related bacteria, suggesting potential for a broader vaccine.

## Contribution

The study identifies OmpA2 as a promising antigen for a cross-protective vaccine against multiple Burkholderia species and Pseudomonas aeruginosa.

## Key findings

- Antibodies to OmpA2 show highest cross-reactivity with B. cepacia complex and Pseudomonas aeruginosa.
- T cells from Pal and OmpA2 vaccines respond to B. cepacia complex homologues.
- Nanovaccine-induced antibodies bind distantly related proteins in P. aeruginosa.

## Abstract

Burkholderia pseudomallei complex and B. cepacia complex are two evolutionary distinct clades of pathogens causing human disease. Most vaccine efforts have focused on the former group largely due to their biothreat status and global disease burden. It has been proposed that a vaccine could be developed that simultaneously protects against both groups of Burkholderia by specifically targeting conserved antigens. Only a few studies have set out to identify which antigens may be optimal targets for such a vaccine. We have previously assessed the ability of three highly conserved B. pseudomallei antigens, namely OmpA1, OmpA2, and Pal, coupled to gold nanoparticle vaccines, to protect mice against a homotypic B. pseudomallei challenge. Here, we have expanded our study by demonstrating that antibodies to each of these proteins show varying levels of reactivity to homologues in B. cepacia complex, with OmpA2 antibodies exhibiting the highest cross-reactivity. Remarkably, some nanovaccine immunized mice, particularly those that received OmpA2, produced antibodies that bind Pseudomonas aeruginosa, which harbors distantly related homologous proteins. T cells elicited to Pal and OmpA2 responded to stimulation with B. cepacia complex-derived homologues. Our study supports incorporation of these antigens, particularly OmpA2, for the development of a pan-Burkholderia vaccine.