Monoclonal antibodies against glycoprotein of Ebola sudan boniface virus
Inventors
Dye, John M. • Kuehne, Ana I. • Guest, Shawn B.
Assignees
US Army Medical Research and Development Command
Publication Number
US-9097713-B2
Publication Date
2015-08-04
Expiration Date
2030-09-01
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Abstract
We disclose Ebola Sudan Boniface virus GP Monoclonal antibodies, epitopes recognized by these monoclonal antibodies, and the sequences of the variable regions of some of these antibodies. Also provided are mixtures of antibodies of the present invention, as well as methods of using individual antibodies or mixtures thereof for the detection, prevention, and/or therapeutic treatment of Ebola Sudan Boniface virus infections in vitro and in vivo.
Core Innovation
The invention provides monoclonal antibodies (MAbs) against glycoproteins (GPs) of the Ebola Sudan Boniface Virus (ESB). These antibodies specifically recognize epitopes on the ESB GP and include sequences of the variable regions of certain antibodies such as 16H11, 19B3, 17F6, and 16F6. The invention includes individual antibodies, mixtures of these antibodies, hybridoma cells producing them, and methods for their use in detection, prevention, and therapeutic treatment of Ebola Sudan Boniface virus infections both in vitro and in vivo.
The problem addressed is the lack of known antibodies targeting the Sudan Boniface species of the Ebola virus. Prior research largely focused on the Zaire species, with existing monoclonal antibodies specific to Ebola Zaire but none known against Sudan Boniface virus, which is antigenically distinct and causes significant outbreaks with considerable lethality. The invention solves the need for antibodies specific to Sudan Boniface virus to enable specific detection, diagnostic applications, and therapeutic interventions.
The glycoprotein (GP) of Ebola virus is the sole viral protein responsible for viral attachment, fusion, and entry into host cells, making it a critical target for neutralizing antibodies and vaccine development. The monoclonal antibodies of this invention bind to conformational epitopes on the Sudan Boniface GP sequence and have been shown to provide protection prophylactically and therapeutically in experiments. Recognition of unique epitopes on Sudan Boniface GP supports the development of specific diagnostics and therapeutics that do not cross-react with other Ebola strains, addressing the antigenic diversity within ebolavirus species.
Claims Coverage
The patent presents one independent claim covering an isolated monoclonal antibody and its features, along with related dependent claims addressing compositions, methods of inhibition, detection, and kits. The inventive features focus on antibody structure, specificity, and functional applications.
Isolated monoclonal antibody with specified variable regions binding Ebola Sudan Boniface GP
An isolated monoclonal antibody comprising a heavy chain variable region with at least 90% sequence identity to SEQ ID NO: 8 and a light chain variable region with at least 90% sequence identity to SEQ ID NO: 10. The heavy chain includes residues Glu23, Val24, Lys99 and comprises three complementarity determining regions (CDRs) at defined amino acid positions corresponding to SEQ ID NO: 8. The light chain variable region comprises three CDRs matching SEQ ID NOS: 23, 24, and 25. This antibody specifically binds Ebola Sudan Boniface virus glycoprotein (GP).
Monoclonal antibody comprising exact heavy and light chain variable region sequences
A monoclonal antibody where the heavy chain variable region is the exact amino acid sequence of SEQ ID NO: 8 and the light chain variable region is the exact amino acid sequence of SEQ ID NO: 10.
Composition containing isolated monoclonal antibody
A composition that comprises the isolated monoclonal antibody described, potentially formulated for pharmaceutical use.
Pharmaceutical composition with monoclonal antibody and excipient
A pharmaceutical composition comprising the isolated monoclonal antibody along with a pharmaceutically acceptable excipient suitable for administration.
Method for inhibiting Ebola Sudan Boniface virus replication
A method to inhibit the replication of Ebola Sudan Boniface virus in a mammal by administering an effective amount of the composition containing the monoclonal antibody.
Method of detection of Ebola Sudan Boniface virus in samples
A method comprising incubating a sample with the monoclonal antibody to allow complex formation with the virus, removing unbound antibody, and detecting the antibody-virus complex, where detection indicates the presence or absence of the virus in the sample.
Detection kit for Ebola Sudan Boniface virus
A kit for detecting the virus in biological samples comprising a container holding the isolated monoclonal antibody and instructions for forming and detecting an immunological complex, wherein presence or absence of this complex correlates with virus presence or absence.
The claims cover an isolated monoclonal antibody with specifically defined variable region sequences binding the Ebola Sudan Boniface virus glycoprotein, compositions comprising these antibodies, methods for therapeutic and diagnostic use, and detection kits. These inventive features define the antibody structure, specificity to ESB GP, and practical applications for treatment and detection.
Stated Advantages
These monoclonal antibodies specifically recognize Ebola Sudan Boniface virus with no cross-reactivity to other Ebola strains, allowing precise identification in outbreak situations.
They are effective prophylactic and therapeutic agents that protect against Ebola Sudan Boniface virus infection in vitro and in vivo.
The antibodies facilitate improved detection, enabling sensitive and specific diagnostic assays and immunological test kits for Ebola Sudan Boniface virus.
Antibodies can be humanized or produced in various systems, enhancing suitability for therapeutic use in humans with reduced immunogenicity and improved safety.
Documented Applications
Therapeutic treatment of Ebola Sudan Boniface virus infections in mammals by administering the monoclonal antibodies in effective amounts.
Prophylactic prevention of Ebola Sudan Boniface virus infection by administration of the antibodies before exposure.
Diagnostic detection of Ebola Sudan Boniface virus in biological or environmental samples using immunoassays based on these monoclonal antibodies.
Use in immunoprobes and test kits comprising antibodies for detection of the virus to form immunological complexes as an indicator of virus presence.
Passive vaccination using antibody compositions combining monoclonal antibodies with pharmaceutically acceptable carriers or excipients.
Development of vaccines based on identified antigenic epitopes from the ESB GP to induce protective immune responses.
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