As new disease threats arise and existing pathogens grow resistant to conventional interventions, attention increasingly focuses on the development of vaccines to induce protective immune responses. Given their admirable safety records, protein subunit vaccines are attractive for widespread immunization, but their disadvantages include poor immunogenicity and expensive manufacture. We previously showed that engineered Escherichia coli outer membrane vesicles (OMVs) are an easily purified vaccine-delivery system capable of greatly enhancing the immunogenicity of a low-immunogenicity protein antigen without added adjuvants. Here, we expand the OMV vaccine delivery platform to include carbohydrate antigens. Because carbohydrates are weak stimulators of the adaptive immune system, current carbohydrate-based vaccines require significant modifications and downstream processing to increase their immunogenicity. Using OMV technology, these additional modifications can be circumvented. Specifically, we have engineered E. coli to recombinantly produce OMVs decorated with carbohydrate O-antigens from Francisella tularensis, a highly infectious bacterial pathogen and biowarfare agent. Our results show that these �glycoengineered� OMVs are able to deliver the O-antigens to immune system-associated dendritic cells. Moreover, preliminary immunisations in mice show that these OMVs induce production of O-antigen-specific antibodies and confer protection against lethal challenge with F. tularensis. With the diverse collection of heterologous O-antigens that can be functionally produced in E. coli and localized in OMVs, this work signals the possibility of glycoengineered OMVs as a robust and tunable technology platform for a new generation of prophylactic and therapeutic vaccines.

Scalable biosynthesis of glycoengineered outer membrane vesicles that elicit protective antibodies

247th National Meeting (2014)

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