Статья

A bacterial extracellular vesicle‐based intranasal vaccine against SARS‐CoV‐2 protects against disease and elicits neutralizing antibodies to wild‐type and Delta variants

Linglei JiangDepartment of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore MD USATom A. P. DriedonksDepartment of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore MD USAWouter S. P. JongAbera Bioscience AB Uppsala SwedenSantosh DhakalW. Harry Feinstone Department of Molecular Microbiology and Immunology The Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USAH. Bart van den Berg van SaparoeaAbera Bioscience AB Uppsala SwedenIoannis SitarasW. Harry Feinstone Department of Molecular Microbiology and Immunology The Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USARuifeng ZhouW. Harry Feinstone Department of Molecular Microbiology and Immunology The Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USAChristopher CaputoW. Harry Feinstone Department of Molecular Microbiology and Immunology The Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USAKirsten LittlefieldW. Harry Feinstone Department of Molecular Microbiology and Immunology The Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USAMaggie LowmanDepartment of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore MD USAMengfei ChenDepartment of Otolaryngology‐Head and Neck Surgery Johns Hopkins University School of Medicine Baltimore MD USAGabriela Trzewikoswki de LimaDepartment of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore MD USAОлеся ГололобоваDepartment of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore MD USABarbara J. SmithDepartment of Cell Biology Johns Hopkins University School of Medicine Baltimore MD USAVasiliki MahairakiDepartment of Genetic Medicine and The Richman Family Precision Medicine Centre of Excellence in Alzheimer's Disease Johns Hopkins University School of Medicine Baltimore Maryland USAMorgan R. RichardsonDepartment of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore MD USAKathleen R. MulkaDepartment of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore MD USAAndrew P. LaneDepartment of Otolaryngology‐Head and Neck Surgery Johns Hopkins University School of Medicine Baltimore MD USASabra L. KleinW. Harry Feinstone Department of Molecular Microbiology and Immunology The Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USAAndrew PekoszW. Harry Feinstone Department of Molecular Microbiology and Immunology The Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USACory BraytonDepartment of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore MD USAJoseph L. MankowskiDepartment of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore MD USAJoen LuirinkAbera Bioscience AB Uppsala SwedenJason VillanoDepartment of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore MD USAKenneth W. WitwerDepartment of Genetic Medicine and The Richman Family Precision Medicine Centre of Excellence in Alzheimer's Disease Johns Hopkins University School of Medicine Baltimore Maryland USA

2022en

ABI

Аннотация

Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, desirability of different routes of administration, and emergence of SARS-CoV-2 variants such as the Delta variant. Here, we present a novel, well-characterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden Syrian hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titres of blood anti-RBD IgG as well as detectable mucosal responses. Neutralizing antibody activity against wild-type and Delta variants was evident in all vaccinated subjects. Upon challenge with live virus, hamsters immunized with RBD-OMV, but not animals immunized with unconjugated OMVs or a vehicle control, avoided body mass loss, had lower virus titres in bronchoalveolar lavage fluid, and experienced less severe lung pathology. Our results emphasize the value and versatility of OMV-based vaccine approaches.

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Идентификаторы

DOI: 10.1002/jev2.12192

Цитирования и источники

Цитирований: 2Использованных источников: 0

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