Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives

Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance...

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Main Authors: Ayesha Zahid, Hazrat Ismail, Jennifer C. Wilson, I. Darren Grice
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/7/767
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author Ayesha Zahid
Hazrat Ismail
Jennifer C. Wilson
I. Darren Grice
author_facet Ayesha Zahid
Hazrat Ismail
Jennifer C. Wilson
I. Darren Grice
author_sort Ayesha Zahid
collection DOAJ
description Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic immunogenicity, adjuvant properties, and scalability establish OMVs as potent tools for combating infectious diseases and cancer. Recent advancements in genetic engineering and biotechnology have further expanded the utility of OMVs, enabling the incorporation of multiple epitopes and antigens from diverse pathogens. These developments address critical challenges such as antigenic variability and co-infections, offering broader immune coverage and cost-effective solutions. This review explores the unique structural and immunological properties of OMVs, emphasizing their capacity to elicit robust immune responses. It critically examines established and emerging engineering strategies, including the genetic engineering of surface-displayed antigens, surface conjugation, glycoengineering, nanoparticle-based OMV engineering, hybrid OMVs, and in situ OMV production, among others. Furthermore, recent advancements in preclinical research on OMV-based vaccines, including synthetic OMVs, OMV-based nanorobots, and nanodiscs, as well as emerging isolation and purification methods, are discussed. Lastly, future directions are proposed, highlighting the potential integration of synthetic biology techniques to accelerate research on OMV engineering.
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spelling doaj-art-13e61355ef444c3da247e9e80990d9ac2025-08-20T02:47:06ZengMDPI AGVaccines2076-393X2025-07-0113776710.3390/vaccines13070767Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and PerspectivesAyesha Zahid0Hazrat Ismail1Jennifer C. Wilson2I. Darren Grice3Institute for Biomedicine and Glycomics, Griffith University, Gold Coast, QLD 4222, AustraliaMOE Key Laboratory for Membraneless Organelles & Cellular Dynamics and CAS Center for Excellence in Molecular Cell Science, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, ChinaSchool of Pharmacy and Medical Science, Griffith University, Gold Coast, QLD 4222, AustraliaInstitute for Biomedicine and Glycomics, Griffith University, Gold Coast, QLD 4222, AustraliaOuter-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic immunogenicity, adjuvant properties, and scalability establish OMVs as potent tools for combating infectious diseases and cancer. Recent advancements in genetic engineering and biotechnology have further expanded the utility of OMVs, enabling the incorporation of multiple epitopes and antigens from diverse pathogens. These developments address critical challenges such as antigenic variability and co-infections, offering broader immune coverage and cost-effective solutions. This review explores the unique structural and immunological properties of OMVs, emphasizing their capacity to elicit robust immune responses. It critically examines established and emerging engineering strategies, including the genetic engineering of surface-displayed antigens, surface conjugation, glycoengineering, nanoparticle-based OMV engineering, hybrid OMVs, and in situ OMV production, among others. Furthermore, recent advancements in preclinical research on OMV-based vaccines, including synthetic OMVs, OMV-based nanorobots, and nanodiscs, as well as emerging isolation and purification methods, are discussed. Lastly, future directions are proposed, highlighting the potential integration of synthetic biology techniques to accelerate research on OMV engineering.https://www.mdpi.com/2076-393X/13/7/767outer membrane vesiclesbioengineered vaccinesvaccine developmentgenetic engineeringcancer vaccinesmulti-antigen vaccines
spellingShingle Ayesha Zahid
Hazrat Ismail
Jennifer C. Wilson
I. Darren Grice
Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives
Vaccines
outer membrane vesicles
bioengineered vaccines
vaccine development
genetic engineering
cancer vaccines
multi-antigen vaccines
title Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives
title_full Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives
title_fullStr Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives
title_full_unstemmed Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives
title_short Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives
title_sort bioengineering outer membrane vesicles for vaccine development strategies advances and perspectives
topic outer membrane vesicles
bioengineered vaccines
vaccine development
genetic engineering
cancer vaccines
multi-antigen vaccines
url https://www.mdpi.com/2076-393X/13/7/767
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