Peptide fragments from filoviruses and their uses
Inventors
Assignees
US Department of Health and Human Services
Publication Number
US-11833199-B2
Publication Date
2023-12-05
Expiration Date
2037-10-31
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Abstract
Isolated peptides comprising one or more antigenic sites of filovirus glycoprotein and methods of their use and production are disclosed. Nucleic acid molecules encoding the peptides are also provided. In several embodiments, the peptides can be used to induce an immune response to filovirus glycoprotein, such as Zaire ebolavirus glycoprotein, in a subject, for example, to treat or prevent infection of the subject with the virus.
Core Innovation
The invention discloses isolated peptides comprising one or more antigenic sites of filovirus glycoprotein (GP), including epitopes from ebolavirus GP, such as Zaire ebolavirus glycoprotein, that induce a neutralizing immune response in a subject. These peptides can be used to induce an immune response to filovirus GP to treat or prevent infection with the virus. Nucleic acid molecules encoding these peptides and immunogenic compositions comprising the peptides, nucleic acids, or expression vectors including the nucleic acids are also provided. The peptides can be conjugated to carriers to facilitate immune presentation and can be administered with adjuvants to enhance immunogenicity.
The problem being solved addresses the urgent need for effective vaccines against ebolavirus, especially considering the severe 2014 epidemic and the risk of future outbreaks. Protective immunity is partially attributable to humoral responses, but no single assay is predictive of protection, and difficulties in conducting adequate randomized controlled trials further impede vaccine development. The disclosed peptides and compositions aim to provide well-defined immunogens that elicit neutralizing immune responses to filovirus GP, facilitating vaccine preparedness and control of outbreaks.
Claims Coverage
The patent claims focus on methods for generating an immune response in a subject using isolated peptides comprising specific filovirus GP antigenic sites, with inventive features relating to peptide sequences, conjugation to carriers, and immunization methods.
Use of a defined peptide sequence to induce immune response
A method of generating an immune response to ebolavirus glycoprotein in a subject by administering an effective amount of a peptide comprising the amino acid sequence set forth as SEQ ID NO: 3, with the peptide being no more than 40 amino acids in length.
Specificity for ebolavirus strains
The method wherein the ebolavirus is selected from Zaire ebolavirus, Mayinga ebolavirus, Kikwit ebolavirus, or Makona ebolavirus, targeting these strains for immune response induction.
Peptide conjugation to heterologous carrier
The peptide is linked to a heterologous carrier molecule, optionally via a linker, which can be a peptide linker, forming fusion proteins or conjugates to enhance immunogenicity.
Selection of carrier proteins
Carriers include a list of proteins such as Keyhole Limpet Hemocyanin (KLH), Concholepas Hemocyanin (CCH), Ovalbumin (OVA), bovine serum albumin, tetanus toxoid, diphtheria toxoid, and bacterial toxins or variants thereof, providing diverse options for conjugation.
Peptide sequence definitions
The peptide administered can consist of or consist essentially of the amino acid sequence SEQ ID NO: 3 or the antigenic site V.7 sequence set forth as SEQ ID NO: 3.
Subject selection criteria and therapeutic effect
Methods include selecting subjects who have or are at risk of ebolavirus infection, where the induced immune response inhibits or treats ebolavirus infection.
The claims comprehensively cover methods of immunization using defined minimal peptide fragments of ebolavirus glycoprotein, with sequences specifically set forth as SEQ ID NO: 3, linked or unlinked to carriers, targeting relevant ebolavirus strains, and methods to induce immune responses to prevent or treat infection.
Stated Advantages
Development of peptides that induce a neutralizing immune response capable of protecting against ebolavirus infection.
Broad epitope repertoire induced by optimal dosages, enhancing vaccine efficacy.
Identification of IgM antibodies as important contributors to virus neutralization.
Peptide vaccines allow for focused immune responses to conserved and protective antigenic sites across diverse ebolavirus strains.
Documented Applications
Use of isolated peptides comprising filovirus GP antigenic sites to induce immune responses in mammals, including humans, for treatment or prevention of ebolavirus infection.
Development of immunogenic compositions including peptides, nucleic acids encoding peptides, or vectors expressing peptides as vaccines against ebolavirus.
Use of peptides and immunogenic compositions in prime-boost vaccination protocols for enhanced immunity.
Methods for detection and diagnosis of filovirus infection by detecting antibodies to filovirus GP using isolated peptides.
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