Recent highlights in bacterial extracellular vesicles: From immune host response to vaccine development
Recent highlights in bacterial extracellular vesicles: From immune host response to vaccine development
Sepideh Meidaninikjeh,1Sepideh Palizban,2Nasim Sabouni,3Ata Khosh Lahni,4Fatah Kashanchi,5Reza Jafari,6,*
1. PhD of Microbiology, Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran 2. Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran. 3. Department of Immunology, Mashhad University of Medical Sciences, Mashhad, Iran. 4. Department of Clinical Laboratory Sciences, Ardabil Branch, Islamic Azad University, Ardabil, Iran. 5. Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, VA, USA. 6. Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
Introduction: Extracellular vesicles (EVs) are double-layer spherical structures which are released by both mammal cells and bacteria. According to their size, they are divided into different groups including exosomes, macrovesicles, and apoptotic bodies [1, 2]. It is believed that bacterial extracellular vesicles (BEVs) are a form of common language for bacteria-host communications. They are produced by both gram-positive and also gram-negative bacteria. These structures regulate bacteria-host and bacteria-bacteria interactions, which lead to promoting health or causing disease by delivering virulence factors [3]. Studies have reported EVs fundamental roles in metabolisms, homeostasis, and immune system regulation [4, 5]. As EVs are different in size, origin and content, they can impact the infection and immune system outcomes such as delivering virulence factors, inflammation, cell death, cell survival, pathogen entry, and survival in the host cells [3]. It was shown that BEVs can be used as an acellular vaccine, because they contain immunogenic antigens which are safer than live pathogenic bacteria and can stimulate immune response in the host [6].
Methods: In this study, articles from Web of Sciences and Scopus databases were searched with bacterial extracellular vesicles (BEVs), immune system, and vaccine keywords. Duplicate articles were removed, and finally 224 English language articles were selected and reviewed.
Results: Vaccines, as a great revolution in the medical world to help human health, still have many undiscovered venues where the research continues to develop and optimize the effectiveness of vaccines with different platforms with particular therapeutic goals [7]. Vaccines are great choice to in the management of infectious disease, although there are not any approved vaccines for a number of infectious disease or illness [8]. BEVs of gram-positive and negative bacteria have lipids, nucleic acids, proteins carbohydrates and other component of bacterial structures. Therefore, it was shown that BEVs can be used as an acellular vaccine, because they contain immunogenic antigens which are safer than live pathogenic bacteria and can stimulate immune response in the host [6]. BEVs enable stimulation and modulation of the innate and adaptive immune system at a suitable and long-term level without pathogenicity as the main golden goal in vaccine design. They have the ability to transport and store bacterial component including proteins, lipids, DNA, and RNA. They can also evade from degradation mechanisms of the host. However, they have some limitations such as BEVs and bacteriotoxin aggregation in the hosts, high cost of isolation, low level of bacterial component expression, and interaction with immune-suppressive molecules of the immune system [9]. The first OMV-vaccines were produced based on Good Manufacturing Practice (GMP) rules for Neisseria meningitidis serogroup B (dOMVB) via detergent extraction method that exerts a promising performance to delivery of meningococcal antigens and providing protective immune responses. In later years, OMV isolated from N. meningitidis, serogroup A (dOMVA), X (dOMVX), and W (dOMVW), were developed in a similar manner [6]. Candidate vaccines based on BEVs are also in preclinical development against bacterial species including Bordetella pertussis, M. tuberculosis, S. Typhimurium, Vibrio cholerae, and Klebsiella pneumoniae. These vaccines have been demonstrated to effectively stimulate both humoral and cellular immunity [10].
Conclusion: BEVs are potential to design vaccine, but more studies are needed to understand different mechanisms of their entry into the host cells, and pathogenicity, especially in gram-positive bacteria.