Abstract
The prevailing pandemic of SARS-CoV-2 highlights the desperate need of alternative vaccine-platforms, which are safe, effective, and can be modified to carry antigens of emerging pathogens. The current SARS-CoV-2 vaccines based on mRNA and adenoviral vector technology meet some of these criteria but still face limitations regarding administration route, mass production, stability, and storage. Herein, we introduce a novel SARS-CoV-2 vaccine candidate based on bacterial outer membrane vesicles (OMVs). Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) have been genetically modified to produce increased amounts of detoxified OMVs decorated with the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein. Intranasal immunization with RBD-decorated OMVs induced not only a robust immune response against the bacterial outer membrane components but also detectable antibody titers against the Spike protein. Cell culture infection assays using a Spike-pseudotyped lentivirus confirmed the presence of SARS-CoV-2 neutralizing antibodies. Highest titers against the SARS-CoV-2 Spike protein and most potent neutralization activity were observed for an alternating immunization regimen using RBD-decorated OMVs from ETEC and V. cholerae in turn. These results highlight the versatile vaccine applications offered by OMVs via expression of heterologous antigens in the donor bacterium.
Highlights
Vaccines were invented over 200 years ago, with the recombinant vaccine era beginning in 1981 (Plotkin, 2014)
Genetic engineering of donor strains allowed a deeper characterization of outer membrane vesicles (OMVs) derived from V. cholerae and enterotoxigenic Escherichia coli (ETEC)
We focused on the development of a mucosally delivered, vesicle-based, subunit vaccine, which can stimulate a robust immune response directed against the SARS-CoV2 Spike protein
Summary
Vaccines were invented over 200 years ago, with the recombinant vaccine era beginning in 1981 (Plotkin, 2014). Despite this long experience, generation of effective vaccines against emerging pathogens remains exceedingly difficult and still retains a significant empirical component. The current pandemic of SARS-CoV-2 highlights the desperate need of versatile vaccine-platforms, which can be modified to carry antigens of emerging pathogens. The current and future pandemic outbreaks still warrant that we take a broad approach in developing safe and OMV-Based Vaccine Against SARS-CoV-2 effective vaccine candidates. We present an outer membrane vesicle (OMV)-based vaccine candidate that is decorated with the receptor binding domain (RBD) of the SARSCoV-2 Spike protein
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