Coxiella burnetii epitopes for T cell-targeted Q fever vaccines
Inventors
Poznansky, Mark C. • Sluder, Ann Elizabeth • Brauns, Timothy Alan • De Groot, Anne Searls • Moise, Leonard Jeffrey • Garritsen, Anja • Scholzen, Anja
Assignees
Innatoss Laboratories Bv • General Hospital Corp • Epivax Inc
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Publication Number
US-11690902-B2
Publication Date
2023-07-04
Expiration Date
Abstract
Compositions and methods for inducing a protective immune response against Coxiella burnetii, to reduce a subject's risk of developing Q fever.
Core Innovation
The described invention addresses Q fever using an immunoinformatics-driven selection of Coxiella burnetii T-cell epitopes. It predicts HLA class I and HLA class II epitope candidates that are conserved across strains and provides a defined multi-epitope vaccine concept centered on selected Coxiella burnetii source antigens. The selected epitopes are mapped to HLA binding context using HLA-A/B supertypes and specific HLA-DR alleles including DRB1*0101, *0301, *0401, *0701, *0801, *1101, *1301, and *1501.
The invention describes validation of epitope selection using HLA binding competition assays to confirm binding accuracy for the predicted candidates. It further confirms de novo immunogenicity of class II epitopes in HLA-DR3 transgenic mice for the selected set of HLA class II epitopes. In addition, it reports human ex vivo IFN-γ ELISpot recall using naturally exposed individuals, with recall observed for a subset of the class II epitopes and with sparse HLA class I recall.
The described concept supports vaccine delivery using multi-epitope peptide concatemers and nucleic acids encoding the same, optionally linked by linkers. The document describes further polypeptide architecture options, including optional fusion to Mycobacterium tuberculosis Hsp70 and inclusion of B-cell-associated Com1 fusions. It also provides formats for nucleic-acid delivery using viral vectors and RNA transcript forms, and it reports minimal reactogenicity of the tested peptides in a guinea pig delayed-type hypersensitivity model.
Claims Coverage
The document contains one independent claim covering a nucleic-acid-based Q fever composition that encodes a defined multi-epitope Coxiella burnetii polypeptide, optionally linked by linkers, and formulated with a pharmaceutically acceptable carrier. The dependent claims further add specific additional epitope peptides and constrain the nucleic-acid delivery format and polypeptide architecture.
Multi-epitope Coxiella burnetii nucleic-acid-encoded polypeptide
A composition comprising one or more isolated nucleic acids encoding a polypeptide comprising three or more epitope peptides of Coxiella burnetti source antigens, wherein the three or more epitope peptides are selected from p4, p12, p14, p15, p17, p18, p20, p21, p22, p26, p27, p30, p37, p38, p42, p43, p45, and p48, each of which consists of SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO:18, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 30, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 45, and SEQ ID NO: 48 respectively, optionally with linkers therebetween, and a pharmaceutically acceptable carrier.
Expanded set of additional Coxiella burnetii epitope peptides
The composition of the independent claim includes a polypeptide that further comprises additional Coxiella burnetii epitope peptides p2, p6, p19, p23, p24, p31, p46, p47, and p50, each defined by a corresponding SEQ ID NO.
Viral vector delivery of the encoded nucleic acids
The one or more nucleic acids are delivered in an adenoviral vector or a vaccinia viral vector.
RNA transcript format for nucleic-acid delivery
The one or more nucleic acids are present in an RNA transcript.
Concatemer arrangement of three or more epitope peptides
The three or more epitope peptides are in the form of concatemers.
Concatemer fusion to Mycobacterium tuberculosis Hsp70
A polypeptide made of concatemers is fused to Mycobacterium tuberculosis Hsp70.
Overall, the claims focus on a pharmaceutically acceptable composition including one or more isolated nucleic acids encoding a polypeptide with a defined set of three or more Coxiella burnetii epitope peptides, each tied to specified SEQ ID NOs, optionally linked by linkers. Coverage is broadened by adding further SEQ ID-defined epitope peptides and narrowed by specifying viral vector or RNA transcript delivery formats and by constraining the polypeptide to concatemer and optional fusion to Mycobacterium tuberculosis Hsp70.
Stated Advantages
Documented Applications
No documented applications found
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