Multivalent Epstein-Barr virus-like particles and uses thereof
Inventors
Ogembo, Javier Gordon • MUTSVUNGUMA, Lorraine Zvichapera • WUSSOW, Felix
Assignees
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Publication Number
US-12303559-B2
Publication Date
2025-05-20
Expiration Date
Abstract
Disclosed are vaccine compositions comprising a VLP comprising two or more EBV envelope glycoproteins and one or more T cell antigens and methods of preventing or treating EBV infections using the vaccine compositions. Also disclosed is an expression system or a single expression vector for co-expressing two or more EBV envelope glycoproteins simultaneously to generate a VLP vaccine. The expression system may include a single vector inserted with two or more nucleic acid sequences that encode two or more EBV envelope glycoproteins linked by one or more linking sequences such that the EBV envelope glycoproteins are co-expressed simultaneously.
Core Innovation
The disclosure describes an expression system for co-expressing a plurality of EBV envelope glycoproteins. The system uses an expression vector having two or more expression cassettes, where each cassette includes a promoter, a nucleic acid sequence encoding two or more EBV envelope glycoproteins, and one or more linking sequences. The plurality of EBV envelope glycoproteins is co-expressed simultaneously and self-cleaved and/or self-processed.
Through the self-cleaved and/or self-processed co-expression, the EBV envelope glycoproteins assemble into one or more glycoprotein complexes. The disclosure identifies glycoprotein complex examples such as gp42-gH/gL and gB-gH/gL, and states that linking sequences can provide self-processing.
The disclosure also describes multivalent EBV virus-like particle vaccines that comprise EBV envelope glycoproteins and T-cell antigens. In this context, multiple EBV envelope glycoproteins are combined and an expression system or single vector co-expresses multiple EBV envelope glycoproteins simultaneously to enable assembly of glycoprotein complexes. The document further describes expression vectors including polycistronic pCAGGS and MVA-BAC constructs, as well as gene insertion sites and packaging strategies.
Claims Coverage
The independent claims are directed to an expression system and a composition, each enabling simultaneous co-expression of two or more EBV envelope glycoproteins from an expression vector with multiple expression cassettes, where self-cleavage and/or self-processing assembles glycoprotein complexes. The main inventive features center on the multivalent EBV envelope glycoprotein co-expression, the linking strategy, and the resulting glycoprotein complexes.
Simultaneous co-expression and self-cleavage/self-processing assembly of EBV envelope glycoprotein complexes
An expression system for co-expressing a plurality of EBV envelope glycoproteins comprising an expression vector having two or more expression cassettes, wherein each cassette comprises a promoter, a nucleic acid sequence encoding two or more EBV envelope glycoproteins, and one or more linking sequences, wherein the two or more EBV envelope glycoproteins are co-expressed simultaneously, self-cleaved and/or self-processed to assemble into one or more glycoprotein complexes.
Expression vector with multiple expression cassettes enabling co-expression and self-cleavage/self-processing to assemble glycoprotein complexes
A composition comprising an expression vector having two or more expression cassettes, wherein each cassette comprises a promoter, a nucleic acid sequence encoding two or more EBV envelope glycoproteins, and one or more linking sequences, wherein the two or more EBV envelope glycoproteins are co-expressed simultaneously, self-cleaved and/or self-processed to assemble into one or more glycoprotein complexes; and wherein the expression vector is capable of co-expressing a plurality of EBV envelope glycoproteins.
Defined glycoprotein complex pairings
One or more glycoprotein complexes include gp42-gH/gL or gB-gH/gL.
Linking sequences containing 2A sequences for ribosomal skipping
The linking sequences contain 2A sequences encoding 2A peptides that mediate ribosomal skipping.
Expression vector implemented as an MVA vector
The expression vector is an MVA vector.
Two or more expression cassettes inserted into selected insertion sites
The two or more expression cassettes are inserted into insertion sites selected from Del2 insertion site, IGR3 insertion site, G1L/18R insertion site, and Del3 insertion site.
Overall, claim coverage centers on an expression vector architecture with two or more expression cassettes encoding multiple EBV envelope glycoproteins linked by one or more linking sequences, enabling simultaneous co-expression with self-cleavage and/or self-processing to assemble into glycoprotein complexes. The dependent claims further specify representative complex compositions, linking sequences using 2A sequences for ribosomal skipping, embodiments using an MVA vector, and example insertion-site options for cassette placement.
Stated Advantages
Multivalent combinations outperform gp350 alone.
Documented Applications
Preventing or treating an EBV infection or an EBV-associated condition by administering a therapeutically effective amount of the composition.
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