Employing Escherichia coli-derived outer membrane vesicles as an antigen delivery platform elicits protective immunity against Acinetobacter baumannii infection

Abstract

Outer membrane vesicles (OMVs) have proven to be highly immunogenic and induced an immune response against bacterial infection in human clinics and animal models. We sought to investigate whether engineered OMVs can be a feasible antigen-delivery platform for efficiently inducing specific antibody responses. In this study, Omp22 (an outer membrane protein of A. baumannii) was displayed on E. coli DH5α-derived OMVs (Omp22-OMVs) using recombinant gene technology. The morphological features of Omp22-OMVs were similar to those of wild-type OMVs (wtOMVs). Immunization with Omp22-OMVs induced high titers of Omp22-specific antibodies. In a murine sepsis model, Omp22-OMV immunization significantly protected mice from lethal challenge with a clinically isolated A. baumannii strain, which was evidenced by the increased survival rate of the mice, the reduced bacterial burdens in the lung, spleen, liver, kidney, and blood, and the suppressed serum levels of inflammatory cytokines. In vitro opsonophagocytosis assays showed that antiserum collected from Omp22-OMV-immunized mice had bactericidal activity against clinical isolates, which was partly specific antibody-dependent. These results strongly indicated that engineered OMVs could display a whole heterologous protein (~22 kDa) on the surface and effectively induce specific antibody responses, and thus OMVs have the potential to be a feasible vaccine platform.

Engineered outer membrane vesicle is potent to elicit HPV16E7-specific cellular immunity in a mouse model of TC-1 graft tumor

“…[13][14][15][16] The vesicles contain the bacterial outer membrane and periplasm components, including lipopolysaccharides, nucleotide acids, lipids, outer membrane proteins, periplasmic proteins, inner membrane proteins and cytoplasm proteins. [13][14][15][16][17] OMVs were found to be highly immunogenic and elicit efficient immune responses, independent of additional adjuvants, against the bacterium from which they were isolated. 16 However, their potential as a novel antigen delivery carrier has not been well studied.…”

Outer membrane vesicles for vaccination and targeted drug delivery

“…Schematic diagram of the construction of recombinant Omp22‐OMVs. (Reprinted with permission from Huang et al (). Copyright 2016 Springer Nature)…”

Les vaccins dans la prévention des infections associées aux soins

“…Pour les autres bactéries à gram négatif responsables d'IAS, les études vaccinales sont encore à des stades préclinique [78][79][80][81][82]. Des études récentes suggèrent toutefois que l'utilisation des vésicules membranaires des bactéries à gram négatif pourrait être une piste intéressante pour le développement de nouvelles stratégies vaccinales contre les bactéries à gram négatif telles que A. baumanii [83], K. pneumoniae [80] et E. coli [84].…”