Conserved region T cell vaccines for coronavirus and methods of use
Inventors
Korber, Bette T. M. • Theiler, James • BAROUCH, Dan • Weissman, Drew • Hanke, Tomas
Assignees
Oxford University Innovation Ltd • Beth Israel Deaconess Medical Center Inc • University of Pennsylvania Penn • Triad National Security LLC
Publication Number
US-12364750-B1
Publication Date
2025-07-22
Expiration Date
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Abstract
Immunogenic compositions and methods of their use in eliciting immune responses to coronaviruses, such as SARS-CoV-2 are provided.
Core Innovation
Provided herein are immunogenic compositions and methods of their use in eliciting immune responses to coronaviruses, such as SARS-CoV-2. The methods include administering to the subject a composition comprising one or more polypeptides with at least 95% sequence identity (such as at least 99% sequence identity) to any one of SEQ ID NOs: 1-14 and 18 or a composition comprising one or more nucleic acids encoding one or more polypeptides with at least 95% sequence identity (such as at least 99% sequence identity) to any one of SEQ ID NOs: 1-14 and 18, thereby eliciting an immune response to the coronavirus. In particular embodiments, the nucleic acid encoding the one or more polypeptides is mRNA, which in some embodiments is formulated in a lipid nanoparticle (for example ALC-0315), and in other embodiments the nucleic acid is included in an adenovirus vector (for example Ad5, Ad26, Ad35, Ad52, ChAdOx1, or ChAdOx2).
The disclosure addresses the need for vaccines that elicit T cell responses to conserved regions of coronaviruses by targeting the most conserved regions in the viral proteome across a diverse sampling of Sarbecoviruses or the viral diversity that has evolved within the SARS-CoV-2 global pandemic. The conserved region approach uses long contiguous amino acid stretches, including artificial sequences derived using the Epigraph algorithm, to maximize the number of potential epitopes, increase cross-reactive potential, and target regions believed to be under fitness constraints and difficult to escape without a fitness cost.
Claims Coverage
Independent claims identified: 1, 8, and 13. The claims disclose three main inventive features relating to an immunogenic composition, a vector, and a method of eliciting an immune response.
Immunogenic composition comprising conserved region polypeptides or encoding nucleic acids
An immunogenic composition comprising one or more polypeptides with at least 99% sequence identity to any one of SEQ ID NOs: 11-14; or a nucleic acid encoding a polypeptide with at least 99% sequence identity to any one of SEQ ID NOs: 11-14.
Pharmaceutically acceptable carrier for the immunogenic composition
The immunogenic composition further comprises a pharmaceutically acceptable carrier.
Vector comprising nucleic acid encoding conserved region polypeptide
A vector comprising a nucleic acid encoding a polypeptide with at least 99% sequence identity to any one of SEQ ID NOs: 11-14.
Method of eliciting an immune response by administering the disclosed composition
A method of eliciting an immune response to a coronavirus in a subject, comprising administering to the subject the immunogenic composition comprising the disclosed polypeptides or nucleic acids, thereby eliciting an immune response to the coronavirus.
The independent claims cover (1) immunogenic compositions containing one or more polypeptides or nucleic acids corresponding to conserved region sequences (SEQ ID NOs: 11-14) together with a pharmaceutically acceptable carrier, (2) vectors comprising nucleic acids encoding those conserved region polypeptides, and (3) methods of eliciting an immune response by administering the disclosed immunogenic composition.
Stated Advantages
Elicits T cell responses to conserved regions of coronaviruses that are highly likely to be cross-reactive with variants and diverse Sarbecoviruses.
Targets protein regions that are under fitness constraints and would not be able to readily escape immune responses, making escape difficult without a fitness cost.
Uses long contiguous conserved stretches to maximize the number of potential epitopes available for T-cell targeting.
Provides improved virus-specific immunity (e.g., T cell-based immune responses) and increased coverage and representation of immunogenic epitopes by including optimized viral polypeptides and epigraph sequences.
Documented Applications
Eliciting an immune response to a coronavirus (such as SARS-CoV-2) in a subject by administering an immunogenic composition comprising conserved region polypeptides or nucleic acids.
Immunogenic compositions formulated as vaccines, including polypeptide-based vaccines or nucleic acid-based vaccines (for example mRNA formulated in lipid nanoparticles or nucleic acids delivered by adenovirus vectors).
Vectors comprising nucleic acids encoding conserved region polypeptides, including adenovirus vectors such as Ad5, Ad26, Ad35, Ad52, ChAdOx1, or ChAdOx2.
mRNA-LNP formulations encoding disclosed polypeptides, with exemplary lipid nanoparticles including ALC-0315.
Use in prime-boost vaccination regimens, including combinations of disclosed immunogenic compositions and other coronavirus vaccines.
Preclinical evaluation and efficacy testing in mouse models, including intranasal challenge with SARS-CoV-2 to assess viral load and weight loss as measures of vaccine efficacy.
Preventing, treating, or ameliorating coronavirus disease by eliciting immune responses that reduce infection or viral replication.
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