A modular antigen anchoring strategy for cellular nanoparticle vaccines against Burkholderia pseudomallei

Summary

Developing a vaccine against Burkholderia pseudomallei, the bacterium that causes melioidosis, is difficult because protective immunity requires both antibody and T-cell responses and because existing platforms are not easily adapted to complex antigens. In this study, researchers designed a modular 'plug-and-play' nanovaccine: they chemically attached two B. pseudomallei antigens, the protein Hcp1 and the capsular polysaccharide CPS, to lipid anchors, which then inserted spontaneously into the membranes of macrophage-membrane-coated nanoparticles. The resulting antigen-displayed nanoparticles were stable, kept the antigens accessible on the surface, and were taken up efficiently by dendritic cells, driving their maturation and cytokine production. In mice, the formulations generated strong T-cell responses, high-titer antibodies, and germinal center formation, indicating coordinated cellular and humoral immunity. Because antigen attachment is separate from nanoparticle production, the platform could be rapidly reconfigured to combine multiple antigens, offering a generalizable strategy for vaccines against B. pseudomallei and other complex pathogens; no melioidosis vaccine is currently licensed.