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Mol Ther. 2017 Feb 16. pii: S1525-0016(17)30016-3. doi: 10.1016/j.ymthe.2017.01.010. [Epub ahead of print]
Safe Recombinant Outer Membrane Vesicles that Display M2e Elicit Heterologous Influenza Protection.
Watkins HC1, Rappazzo CG1, Higgins JS2, Sun X3, Brock N3, Chau A2, Misra A4, Cannizzo JP5, King MR1, Maines TR3, Leifer CA6, Whittaker GR6, DeLisa MP4, Putnam D7.
Author information
Abstract
Recombinant, Escherichia coli-derived outer membrane vesicles (rOMVs), which display heterologous protein subunits, have potential as a vaccine adjuvant platform. One drawback to rOMVs is their lipopolysaccharide (LPS) content, limiting their translatability to the clinic due to potential adverse effects. Here, we explore a unique rOMV construct with structurally remodeled lipids containing only the lipid IVa portion of LPS, which does not stimulate human TLR4. The rOMVs are derived from a genetically engineered B strain of E. coli, ClearColi, which produces lipid IVa, and which was further engineered in our laboratory to hypervesiculate and make rOMVs. We report that rOMVs derived from this lipid IVa strain have substantially attenuated pyrogenicity yet retain high levels of immunogenicity, promote dendritic cell maturation, and generate a balanced Th1/Th2 humoral response. Additionally, an influenza A virus matrix 2 protein-based antigen displayed on these rOMVs resulted in 100% survival against a lethal challenge with two influenza A virus strains (H1N1 and H3N2) in mice with different genetic backgrounds (BALB/c, C57BL/6, and DBA/2J). Additionally, a two-log reduction of lung viral titer was achieved in a ferret model of influenza infection with human pandemic H1N1. The rOMVs reported herein represent a potentially safe and simple subunit vaccine delivery platform.
Copyright ? 2017 The American Society of Gene and Cell Therapy. All rights reserved.
KEYWORDS:
M2e; adjuvants; endotoxin; influenza; outer membrane vesicles; subunit vaccine delivery
PMID: 28215994 DOI: 10.1016/j.ymthe.2017.01.010
[PubMed - as supplied by publisher]
Safe Recombinant Outer Membrane Vesicles that Display M2e Elicit Heterologous Influenza Protection.
Watkins HC1, Rappazzo CG1, Higgins JS2, Sun X3, Brock N3, Chau A2, Misra A4, Cannizzo JP5, King MR1, Maines TR3, Leifer CA6, Whittaker GR6, DeLisa MP4, Putnam D7.
Author information
Abstract
Recombinant, Escherichia coli-derived outer membrane vesicles (rOMVs), which display heterologous protein subunits, have potential as a vaccine adjuvant platform. One drawback to rOMVs is their lipopolysaccharide (LPS) content, limiting their translatability to the clinic due to potential adverse effects. Here, we explore a unique rOMV construct with structurally remodeled lipids containing only the lipid IVa portion of LPS, which does not stimulate human TLR4. The rOMVs are derived from a genetically engineered B strain of E. coli, ClearColi, which produces lipid IVa, and which was further engineered in our laboratory to hypervesiculate and make rOMVs. We report that rOMVs derived from this lipid IVa strain have substantially attenuated pyrogenicity yet retain high levels of immunogenicity, promote dendritic cell maturation, and generate a balanced Th1/Th2 humoral response. Additionally, an influenza A virus matrix 2 protein-based antigen displayed on these rOMVs resulted in 100% survival against a lethal challenge with two influenza A virus strains (H1N1 and H3N2) in mice with different genetic backgrounds (BALB/c, C57BL/6, and DBA/2J). Additionally, a two-log reduction of lung viral titer was achieved in a ferret model of influenza infection with human pandemic H1N1. The rOMVs reported herein represent a potentially safe and simple subunit vaccine delivery platform.
Copyright ? 2017 The American Society of Gene and Cell Therapy. All rights reserved.
KEYWORDS:
M2e; adjuvants; endotoxin; influenza; outer membrane vesicles; subunit vaccine delivery
PMID: 28215994 DOI: 10.1016/j.ymthe.2017.01.010
[PubMed - as supplied by publisher]