Live attenuated Shigella vaccine
Inventors
Nagy, Gábor • Henics, Tamás • Szijárto, Valeria • Nagy, Eszter
Assignees
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Publication Number
US-9730991-B2
Publication Date
2017-08-15
Expiration Date
Abstract
A live attenuated Shigella vaccine, which is based on a rough Shigella strain lacking LPS O-antigen which is non-invasive through a mutation of the invasion plasmid, specifically for use in the immunoprophylaxis of a subject to prevent infectious diseases, preferably enteral disease, and a Shigella strain, which is a S. flexneri 2a strain with a deletion of the rfb F, ipa B and/or ipa C genes, as well as a recombinant plasmid vector based on a mutated Shigella invasion plasmid comprising a nucleotide sequence encoding at least one heterologous antigen, wherein the plasmid is mutated in at least one of the ipa B and/or ipa C genes.
Core Innovation
The invention provides a live attenuated Shigella vaccine that comprises a non-invasive rough Shigella strain lacking LPS O-antigen. The strain is non-invasive by a mutation in endogenous gene(s) carried in an endogenous invasion plasmid and is not capable of invading eukaryotic cells.
The vaccine further includes attenuation features directed to the endogenous invasion plasmid and to ipa genes, including mutation of ipaB and/or ipaC. In embodiments, the vaccine combines deletion of LPS O-antigen pathway gene(s) with deletion or inactivation of ipaB and/or ipaC to create a non-invasive Shigella that cannot invade eukaryotic cells.
In additional embodiments, the vaccine uses a recombinant endogenous invasion plasmid carrying at least one gene encoding a heterologous antigen. The heterologous antigen gene is positioned such that the at least one antigen is secreted and/or expressed on the bacterial cell surface, supporting serotype-independent cross-protection and heterologous antigen expression.
Claims Coverage
The document includes three independent claims covering a non-invasive rough LPS O-antigen-lacking live attenuated Shigella vaccine, an S. flexneri 2a strain defined by specific deletions, and a mutated Shigella invasion recombinant plasmid vector carrying heterologous antigen sequences.
Non-invasive rough live attenuated Shigella vaccine lacking LPS O-antigen
A live attenuated Shigella vaccine comprising a non-invasive rough Shigella strain lacking LPS O-antigen, which is non-invasive by a mutation in the endogenous gene(s) in an endogenous invasion plasmid and is not capable of invading eukaryotic cells.
S. flexneri 2a strain with rfbF and ipaB/ipaC deletions
An S. flexneri 2a strain comprising a deletion of the rjbF gene and deletion of at least one of the ipaB and/or ipaC genes.
Mutated Shigella invasion recombinant plasmid vector with ipaB/ipaC mutation and heterologous antigen
A mutated Shigella invasion recombinant plasmid vector comprising a mutation in an ipaB and/or ipaC genes, further comprising a nucleotide sequence encoding at least one antigen heterologous to Shigella, wherein said at least one antigen is selected from the group consisting of a bacterial antigen, a viral antigen, a fungal antigen and a parasitic antigen, wherein the Shigella is selected from the group consisting of Shigella dysenteriae, Shigella flexneri, Shigella boydii, and Shigella sonnei.
Overall, claim coverage centers on non-invasive rough Shigella vaccines lacking LPS O-antigen, attenuation via mutations in ipaB and/or ipaC within endogenous invasion plasmid functions, and the encoding of heterologous antigens on mutated Shigella invasion recombinant plasmid vectors.
Stated Advantages
Serotype-independent cross-protection.
Heterologous antigen expression.
Documented Applications
Vaccine.
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