Abstract
The World Health Organization has indicated that we are entering into a post-antibiotic era in which infections that were routinely and successfully treated with antibiotics can now be lethal due to the global dissemination of multidrug resistant strains. Conjugate vaccines are an effective way to create a long-lasting immune response against bacteria. However, these vaccines present many drawbacks such as slow development, high price, and batch-to-batch inconsistencies. Alternate approaches for vaccine development are urgently needed. Here we present a new vaccine consisting of glycoengineered outer membrane vesicles (geOMVs). This platform exploits the fact that the initial steps in the biosynthesis of most bacterial glycans are similar. Therefore, it is possible to easily engineer non-pathogenic Escherichia coli lab strains to produce geOMVs displaying the glycan of the pathogen of interest. In this work we demonstrate the versatility of this platform by showing the efficacy of geOMVs as vaccines against Streptococcus pneumoniae in mice, and against Campylobacter jejuni in chicken. This cost-effective platform could be employed to generate vaccines to prevent infections caused by a wide variety of microbial agents in human and animals.
Highlights
Most successful current antibacterial vaccines are glycoconjugates, composed of cell surface carbohydrates chemically attached to an appropriate carrier protein
We present an alternative platform for vaccines consisting of glycoengineered outer membrane vesicles (OMVs) derived from non-pathogenic engineered Escherichia coli strains expressing bacterial surface glycans encoded by the bacterial pathogenic organisms
We predicted that expressing the S. pneumoniae capsule in an E. coli strain lacking its own O antigen would result in an LPS consisting of capsular polysaccharide attached to the lipid A core
Summary
Most successful current antibacterial vaccines are glycoconjugates, composed of cell surface carbohydrates chemically attached to an appropriate carrier protein These are effective means to generate protective immune responses to prevent a wide range of diseases. ® ® ® based meningococcal vaccines (i.e., MenBvac , MeNZB , and BexSero ) have been successfully developed and employed within various countries[9,10,11,12,13,14,15,16] Due to their success, other OMV vaccine candidates for various pathogenic bacteria including Vibrio cholerae[17,18], Bordetella pertussis[19], Burkholderia pseudomallei[20,21], Acinetobacter baumannii[22] and even Gram-positive bacteria, such as Bacillus anthracis[23], have been tested. As a proof of principle, we demonstrate the efficacy of geOMVs as vaccines for S. pneumoniae serotype 14, and the common foodborne pathogen C. jejuni
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