Predictive and experimental immunogenicity of burkholderia collagen‐like protein 8‐derived antigens

Abstract

Burkholderia pseudomallei is an infectious bacterium of clinical and biodefense concern, and is the causative agent of melioidosis. The mortality rate can reach up to 50% and affects 165,000 people per year; however, there is currently no vaccine available. In this study, we examine the antigen‐specific immune response to a vaccine formulated with antigens derived from an outer membrane protein in B. pseudomallei, Bucl8. Here, we employed a number of bioinformatic tools to predict Bucl8‐derived epitopes that are non‐allergenic and non‐toxic, but would elicit an immune response. From these data, we formulated a vaccine based on two extracellular components of Bucl8, the β‐barrel loops and extended collagen and non‐collagen domains. Outbred CD‐1 mice were immunized with vaccine formulations—composed of recombinant proteins or conjugated synthetic peptides with adjuvant—to assess the antigen‐specific immune responses in mouse sera and lymphoid organs. We found that mice vaccinated with either Bucl8‐derived components gen-erated a robust TH2‐skewed antibody response when antigen was combined with the adjuvant Ad-daVax, while the TH1 response was limited. Mice immunized with synthetic loop peptides had a stronger, more consistent antibody response than recombinant protein antigens, based on higher IgG titers and recognition of bacteria. We then compared peptide‐based vaccines in an established C57BL/6 inbred mouse model and observed a similar TH2‐skewed response. The resulting formulations will be applied in future studies examining the protection of Bucl8‐derived vaccines.