Peptide fragments from filoviruses and their uses
Inventors
Assignees
US Department of Health and Human Services
Publication Number
US-11202824-B2
Publication Date
2021-12-21
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 provides isolated peptides comprising one or more antigenic sites of filovirus glycoprotein (GP), particularly from ebolavirus glycoprotein such as Zaire ebolavirus GP, that induce a neutralizing immune response in a subject. These peptide fragments contain identified antigenic sites capable of eliciting an immune response that neutralizes subsequent infection by the virus. The peptides can be conjugated to carriers to facilitate immune system presentation, and nucleic acid molecules encoding these peptides, as well as expression vectors including these nucleic acids, are also disclosed.
The problem being solved relates to the urgent need for effective Ebola virus vaccines due to the severity of Ebola outbreaks, such as the 2014 epidemic in Western Africa. Protection against Ebola Disease is partially attributed to the humoral immune response; however, no single assay predicts protection, and antibody titers are not clearly correlated with immunity. Additionally, vaccine development is impeded by the difficulty of conducting adequate clinical trials and understanding correlates of protection.
The disclosure overcomes these issues by identifying specific antigenic sites on filovirus GP, providing peptides that elicit neutralizing antibodies, and methods to use these peptides or encoding nucleic acids in immunogenic compositions for vaccination or treatment. Such compositions can induce a protective immune response to prevent or treat filovirus infections, including ebolavirus infections, by targeting well-defined antigenic regions of GP.
Claims Coverage
The patent contains independent claims directed to methods of generating an immune response to ebolavirus glycoprotein (GP) by administering specific peptide antigenic sites. The claims focus on the sequences constituting antigenic site VI peptides and their use in vaccination methods.
Use of specific antigenic site VI peptides to generate an immune response
The method involves selecting a subject with or at risk of ebolavirus infection and administering an effective amount of a peptide comprising or consisting essentially of the antigenic site VI amino acid sequence set forth as SEQ ID NOs: 10, 11, 12, 13, or 53 to generate an immune response that inhibits or treats ebolavirus infection.
Inclusion of specific ebolavirus species in method
The ebolavirus in the method is selected from Zaire ebolavirus, Bundibugyo ebolavirus, Sudan ebolavirus, or Tai Forest ebolavirus.
Linkage of peptide to heterologous carriers
The peptide used in the method can be linked to a heterologous carrier, optionally by a linker, where the carrier can be a heterologous protein linked via a peptide linker to form a fusion protein.
Carrier protein selection
The carrier protein can be keyhole limpet hemocyanin (KLH), Concholepas Concholepas Hemocyanin (CCH), ovalbumin, bovine serum albumin, recombinant bacterial or viral toxins or toxoids (including tetanus and diphtheria toxoids, pertussis toxoid, and others), or combinations thereof.
Method claims directed to peptides consisting essentially of specific antigenic site VI sequences
Claims include administration of peptides consisting of or consisting essentially of the antigenic site VI amino acid sequences set forth as SEQ ID NOs: 10, 11, 12, 13, or 53.
The claims cover methods of inducing protective immune responses against ebolavirus infections using isolated antigenic site VI peptides from filovirus GP, optionally conjugated to carriers, encompassing specified peptide sequences and targeting specific ebolavirus species.
Stated Advantages
Identification of antigenic peptide fragments capable of inducing neutralizing immune responses to filovirus glycoproteins.
Use of peptide immunogens that can be conjugated to carriers to enhance immune presentation and response.
Provision of immunogenic compositions and nucleic acid vectors compatible with various vaccine platforms.
Potential for broader immune coverage by targeting conserved antigenic sites among diverse ebolavirus strains.
Methods enable prophylactic and therapeutic intervention against filovirus infections, including prevention and treatment of Ebola virus disease.
Documented Applications
Use of isolated filovirus glycoprotein peptide fragments or nucleic acid molecules encoding them to induce a neutralizing immune response in a subject against filovirus infection, such as Ebola virus infection.
Development of immunogenic compositions (vaccines) comprising peptides conjugated to carriers or nucleic acids encoding peptides for administration to subjects at risk of or infected with ebolavirus.
Use of peptides and peptide-specific antibodies for diagnostic detection of filovirus infection or immune response monitoring.
Application in prime-boost immunization strategies, including DNA-prime/protein-boost regimens or use of viral vectors.
Evaluation of vaccine efficacy by epitope mapping and antibody neutralization assays utilizing disclosed peptides.
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