scholarly journals An Intranasal Vaccine Based on Outer Membrane Vesicles Against SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Himadri B. Thapa ◽  
Anna M. Müller ◽  
Andrew Camilli ◽  
Stefan Schild
Keyword(s):  
Outer Membrane ◽  
Neutralizing Antibodies ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Spike Protein ◽  
Emerging Pathogens ◽  
Robust Immune Response ◽  
Antibody Titers ◽  
Bacterial Outer Membrane ◽  
Membrane Components

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.

scholarly journals Robust Immune Response Induced by Schistosoma mansoni TSP-2 Antigen Coupled to Bacterial Outer Membrane Vesicles

2021 ◽  
Vol Volume 16 ◽  
pp. 7153-7168
Author(s):  
Mayra M F Barbosa ◽  
Alex I Kanno ◽  
Giovana C Barazzone ◽  
Dunia Rodriguez ◽  
Violeta Pancakova ◽  
...  
Keyword(s):  
Immune Response ◽  
Schistosoma Mansoni ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Robust Immune Response ◽  
Bacterial Outer Membrane

scholarly journals Bacterial Outer Membrane Vesicles as Nano‐Scale Bioreactors: A Fatty Acid Conversion Case Study

ChemCatChem ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4080-4086
Author(s):  
Ji‐Won Song ◽  
Yoonjin Baeg ◽  
Ha‐Yeon Jeong ◽  
Jinwon Lee ◽  
Deok‐Kun Oh ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Nano Scale ◽  
Bacterial Outer Membrane

scholarly journals Aggregatibacter actinomycetemcomitans Leukotoxin Is Delivered to Host Cells in an LFA-1-Indepdendent Manner When Associated with Outer Membrane Vesicles

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 414 ◽  
Author(s):  
Justin Nice ◽  
Nataliya Balashova ◽  
Scott Kachlany ◽  
Evan Koufos ◽  
Eric Krueger ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Membrane Vesicles ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Aggressive Periodontitis ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Type I ◽  
Outer Membranes ◽  
Independent Mechanism ◽  
Bacterial Outer Membrane

The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans, has been associated with localized aggressive periodontitis (LAP). In particular, highly leukotoxic strains of A. actinomycetemcomitans have been more closely associated with this disease, suggesting that LtxA is a key virulence factor for A. actinomycetemcomitans. LtxA is secreted across both the inner and outer membranes via the Type I secretion system, but has also been found to be enriched within outer membrane vesicles (OMVs), derived from the bacterial outer membrane. We have characterized the association of LtxA with OMVs produced by the highly leukotoxic strain, JP2, and investigated the interaction of these OMVs with host cells to understand how LtxA is delivered to host cells in this OMV-associated form. Our results demonstrated that a significant fraction of the secreted LtxA exists in an OMV-associated form. Furthermore, we have discovered that in this OMV-associated form, the toxin is trafficked to host cells by a cholesterol- and receptor-independent mechanism in contrast to the mechanism by which free LtxA is delivered. Because OMV-associated toxin is trafficked to host cells in an entirely different manner than free toxin, this study highlights the importance of studying both free and OMV-associated forms of LtxA to understand A. actinomycetemcomitans virulence.

scholarly journals Bacterial outer membrane vesicles engineered with lipidated antigens as a platform for Staphylococcus aureus vaccine

2019 ◽  
Vol 116 (43) ◽  
pp. 21780-21788 ◽  
Author(s):  
Carmela Irene ◽  
Laura Fantappiè ◽  
Elena Caproni ◽  
Francesca Zerbini ◽  
Andrea Anesi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Vaccine Platform ◽  
Transport Pathway ◽  
Protective Antigens ◽  
Tlr4 Agonist ◽  
Engineering Strategy ◽  
Bacterial Outer Membrane

Bacterial outer membrane vesicles (OMVs) represent an interesting vaccine platform for their built-in adjuvanticity and simplicity of production process. Moreover, OMVs can be decorated with foreign antigens using different synthetic biology approaches. However, the optimal OMV engineering strategy, which should guarantee the OMV compartmentalization of most heterologous antigens in quantities high enough to elicit protective immune responses, remains to be validated. In this work we exploited the lipoprotein transport pathway to engineer OMVs with foreign proteins. Using 5 Staphylococcus aureus protective antigens expressed in Escherichia coli as fusions to a lipoprotein leader sequence, we demonstrated that all 5 antigens accumulated in the vesicular compartment at a concentration ranging from 5 to 20% of total OMV proteins, suggesting that antigen lipidation could be a universal approach for OMV manipulation. Engineered OMVs elicited high, saturating antigen-specific antibody titers when administered to mice in quantities as low as 0.2 μg/dose. Moreover, the expression of lipidated antigens in E. coli BL21(DE3)ΔompAΔmsbBΔpagP was shown to affect the lipopolysaccharide structure, with the result that the TLR4 agonist activity of OMVs was markedly reduced. These results, together with the potent protective activity of engineered OMVs observed in mice challenged with S. aureus Newman strain, makes the 5-combo-OMVs a promising vaccine candidate to be tested in clinics.

scholarly journals Optimizing Production and Purification of Bacterial Outer Membrane Vesicles

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Tyler Pugeda ◽  
Milena Dinu ◽  
Lea Michel ◽  
Timothy Chapman ◽  
Michael Pichichero
Keyword(s):  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Bacterial Outer Membrane

Adjuvant effect of bacterial outer membrane vesicles with penta-acylated lipopolysaccharide on antigen-specific T cell priming

Vaccine ◽  
2011 ◽  
Vol 29 (46) ◽  
pp. 8293-8301 ◽  
Author(s):  
Dong Ho Lee ◽  
Sang-Hyun Kim ◽  
Wonseok Kang ◽  
Yoon Seok Choi ◽  
Sang-Ho Lee ◽  
...  
Keyword(s):  
T Cell ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Adjuvant Effect ◽  
Bacterial Outer Membrane ◽  
T Cell Priming
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