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Glycocalyx and its Functions01:14

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The glycocalyx is a carbohydrate-rich, fuzzy-appearing layer on the outer surface of the cell membrane. It is highly hydrophilic, because of this it attracts large amounts of water to the cell's surface. This aids the cell's interaction with the watery environment and also helps it to obtain substances dissolved in the water. It is also important for cell identification, self/non-self determination, and embryonic development and is used in cell-to-cell attachments to form tissues.
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Gram-negative bacteria utilize sophisticated protein secretion systems to transport proteins across their double-membrane envelope into the extracellular environment or host cells. Based on their mechanism of action, these systems are classified into one-step and two-step pathways.One-Step Secretion Systems (Types I, III, IV, and VI)One-step secretion systems bypass the periplasm entirely, forming a continuous channel that spans both the inner and outer membranes:Type I Secretion System (T1SS):...
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Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
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Microorganisms play a fundamental role in vaccine development, gene therapy, and therapeutic production. Their biological properties are harnessed to advance medicine and public health. Beyond immunization, microorganisms contribute to gut health, antibiotic synthesis, and genetic disease treatment.Live Attenuated and Inactivated VaccinesLive attenuated vaccines, such as the measles, mumps, and rubella (MMR) vaccine, utilize weakened forms of pathogens to closely resemble natural infections.
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Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of...
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A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
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Glycoengineered Outer Membrane Vesicles as a Platform for Vaccine Development.

Ezequiel Valguarnera1, Mario F Feldman1

  • 1Washington University School of Medicine, St. Louis, MO, United States.

Methods in Enzymology
|September 23, 2017
PubMed
Summary
This summary is machine-generated.

Novel glycoengineered outer membrane vesicles (geOMVs) offer a promising new platform for developing vaccines against bacterial infections. This approach engineers bacterial outer membrane vesicles to display specific surface carbohydrates, enhancing their potential as effective antibacterial vaccines.

Keywords:
AntigenEscherichia coliGlycoengineeringLPSOuter membrane vesiclesUTIVaccinegeOMVs

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Area of Science:

  • Vaccinology
  • Microbiology
  • Biotechnology

Background:

  • The rise of the postantibiotic era necessitates new strategies for preventing bacterial infections.
  • Current glycoconjugate vaccines, while effective, face manufacturing challenges including biosafety risks and slow serotype inclusion.
  • Outer membrane vesicles (OMVs) from Gram-negative bacteria are emerging as promising vaccine delivery platforms due to their inherent immunogenicity and potential for engineering.

Purpose of the Study:

  • To develop and validate a novel vaccine platform using engineered outer membrane vesicles (OMVs).
  • To demonstrate the feasibility of displaying specific bacterial surface glycans on OMVs for enhanced immunogenicity.
  • To present a detailed method for preparing glycoengineered OMVs (geOMVs) using a uropathogenic Escherichia coli (UPEC) O25b O-antigen as a proof of concept.

Main Methods:

  • Engineering of OMVs to display specific bacterial surface glycans.
  • Preparation of glycoengineered OMVs (geOMVs) displaying the O-antigen from UPEC serotype O25b.
  • Evaluation of geOMVs in relevant animal models of infection.

Main Results:

  • Engineered OMVs successfully displayed target bacterial glycans on their surface.
  • The developed geOMVs demonstrated efficacy in preclinical animal models of bacterial infection.
  • A detailed protocol for geOMV preparation was established, showcasing a viable new vaccine manufacturing approach.

Conclusions:

  • Glycoengineered OMVs represent a versatile and potentially superior platform for developing next-generation antibacterial vaccines.
  • This technology addresses limitations of current glycoconjugate vaccines, offering a faster and safer route to broader pathogen coverage.
  • The successful demonstration with UPEC O25b highlights the potential of geOMVs against significant bacterial pathogens.