Vaccine composition
Inventors
BISWAS, SUMI • Jin, Jing • DABBS, REBECCA ALICE • LABBÉ, GENEVIEVE MARIE CATHERINE
Assignees
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Publication Number
US-12433944-B2
Publication Date
2025-10-07
Expiration Date
Abstract
The present invention relates to vaccine compositions, most notably vaccine compositions wherein the antigenic component is large, for example over 50 kDa, or multimeric, i.e. comprised of subunits. Such antigenic components are of particular interest, because they may represent antigenic components from pathogens that currently it is not possible to vaccinate against. The invention relates to a composition comprising a particle displaying an antigenic component, wherein said composition comprises an antigenic component comprising a first peptide tag, and a moiety comprising a second peptide tag, wherein the antigenic component and the moiety are linked via an isopeptide bond between said first and second peptide tags, and wherein the antigenic component is over 50 kDa, or alternatively is multimeric.
Core Innovation
The disclosed invention relates to a vaccine composition that includes a virus-like particle displaying an antigenic component. The antigenic component is linked to a particle-forming moiety through an isopeptide bond between paired peptide tags, where the antigenic component comprises a first peptide tag and the moiety comprises a second peptide tag.
In particular embodiments, the antigenic component is over 50 kDa and is multimeric, and the moiety is a hepatitis B virus surface antigen (HBsAg) that multimerises to form the virus-like particle. The tagging strategy supports oriented, repetitive display of large, multimeric antigenic or protein components rather than soluble antigens or random chemical conjugation.
The description further provides that covalent conjugation is mediated by peptide tag pairs such as SpyTag/SpyCatcher, including systems and alternatives for isopeptide-tag mediated linkage. Exemplified antigenic components include HCMV pentamer subunits and RSV-F pre-fusion trimer constructs configured with the tagging strategy for particle display.
Characterization and mouse immunogenicity results are provided comparing virus-like particle conjugates to the corresponding unconjugated antigen proteins. The reported outcomes include stronger serum IgG and neutralizing activity for HCMV pentamer-HBsAg VLP compared to unconjugated pentamer protein, and for RSV-F VLP conjugates compared to RSV-F protein.
Claims Coverage
The independent claims cover a VLP vaccine composition with a covalently linked antigenic component and an HBsAg moiety, where the linkage is specifically defined by an isopeptide bond between SpyTag and SpyCatcher sequence-defined peptide tags. The inventive features focus on multimeric over-50 kDa antigen display on an HBsAg-derived VLP via SpyTag/SpyCatcher isopeptide bond formation, with dependent claims refining linkage context and providing immunogenic or vaccine, kit, pharmaceutical, and example antigenic component structures.
Isopeptide-bonded tagged antigen and HBsAg VLP moiety
A composition comprising a virus-like particle displaying an antigenic component, wherein the antigenic component comprises a first peptide tag and a moiety comprises a second peptide tag, and wherein the antigenic component and the moiety are linked via an isopeptide bond between said first and second peptide tags.
Over-50 kDa multimeric antigenic component
The antigenic component is over 50 kDa and is a multimer.
HBsAg moiety multimerises to form the virus-like particle
The moiety is a surface antigen of the hepatitis B virus (HBsAg) and multimerises to form the virus-like particle.
SpyTag/SpyCatcher sequence-defined isopeptide linkage
The first peptide tag is a SpyTag having the amino acid sequence set out in SEQ ID NO: 30, and the second peptide tag is a SpyCatcher having the amino acid sequence set out in SEQ ID NO: 38.
Linker between moiety and SpyCatcher
The composition further defines that the moiety is connected to the SpyCatcher via a linker.
Immunogenic or vaccine composition context
The composition is defined as an immunogenic composition or a vaccine composition.
Prime and booster immunogenic compositions in a kit
A kit includes a first immunogenic composition and one or more booster compositions, where each includes a second immunogenic composition, and where the first and/or second immunogenic compositions correspond to the composition of the isopeptide-bonded tagged VLP antigen configuration.
HCMV pentamer antigenic component subunits
The antigenic component is an HCMV pentamer made up of one or more of gH, gL, pUL128, pUL130, and pUL131 subunits.
Pharmaceutical composition with pharmaceutically acceptable formulation components
A pharmaceutical composition includes the composition of the tagged VLP antigen configuration together with one or more pharmaceutically acceptable buffer, excipient, carrier, and/or adjuvant components.
Across the independent claim coverage reflected in the provided claim text, the core inventive structure is a VLP displaying an over-50 kDa multimeric antigenic component linked to an HBsAg moiety via an isopeptide bond formed between a SpyTag (SEQ ID NO: 30) and a SpyCatcher (SEQ ID NO: 38), with dependent refinements adding linkage context, kit-based first and booster immunogenic compositions, and specified antigenic component and formulation contexts.
Stated Advantages
Stronger serum IgG and neutralizing activity for HCMV pentamer-HBsAg VLP versus unconjugated pentamer protein.
Stronger immunogenic outcomes for RSV-F VLP conjugates versus RSV-F protein.
Documented Applications
Use as a vaccine composition for eliciting immune responses, including serum IgG and neutralizing activity in mouse immunogenicity experiments.
HCMV pentamer and RSV-F pre-fusion trimer antigen display on an HBsAg-based VLP as described in the constructs and characterization.
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