Recombinant bovine immunodeficiency virus-like particles comprising an influenza HA transmembrane domain and C-terminus
Inventors
Pushko, Peter • Tretyakova, Irina
Assignees
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Publication Number
US-12303560-B2
Publication Date
2025-05-20
Expiration Date
Abstract
Described herein are Bovine immunodeficiency virus gag protein (“Bgag”) recombinant virus like particles (“VLPs”) comprising one or more different types of target pathogen proteins. Also described, are compositions comprising the novel Bgag VLPs and the methods of making and using the novel Bgag VLPs.
Core Innovation
The invention relates to a bovine immunodeficiency virus gag virus like particle (Bgag VLP) that comprises an Influenza HA transmembrane domain and C Terminus (TMCT) and a heterologous antigen. The heterologous antigen is functionally connected to the HA TMCT, and the particle is configured to present influenza-associated TMCT linked antigenic components in association with a heterologous antigen within the particle.
The document further describes Bgag VLP variants in which the heterologous antigen and/or its functional portion are positioned such that the antigen is presented on the VLP surface context. It emphasizes antigen expression and co-localization on the Bgag VLP membrane and describes Bgag VLPs carrying influenza HA and NA components, with HA/NA components showing functional activity including hemagglutination and neuraminidase enzymatic activity.
A further aspect of the invention is directed to methods of making the Bgag VLP using a transfer vector plasmid, a carrier virus, and infection of eukaryotic cells. The method includes cloning a transfer vector plasmid comprising a Bgag gene, one or more genes encoding an Influenza HA TMCT, and one or more genes encoding a heterologous antigen, with a promoter operably linked to the Bgag gene and the TMCT genes, followed by carrier virus preparation and infection of eukaryotic cells to produce the Bgag VLP.
Claims Coverage
The partial content provides two independent claims. Together, the claims identify inventive features centered on Bgag VLP composition with HA TMCT and a heterologous antigen functionally connected to the TMCT, and on a Bgag VLP manufacturing workflow using a single transfer vector approach to produce the particle in eukaryotic cells.
Influenza HA TMCT-connected heterologous antigen on Bgag VLP
A bovine immunodeficiency virus gag virus like particle (Bgag VLP) comprising an Influenza HA transmembrane domain and C Terminus (TMCT) and a heterologous antigen, wherein the heterologous antigen is functionally connected to the HA TMCT.
Single transfer vector plasmid carrier virus production of Bgag VLP
A method of making a bovine immunodeficiency virus gag virus like particle (Bgag VLP), comprising cloning a transfer vector plasmid comprising a bovine immunodeficiency virus gag (Bgag) gene, one or more genes encoding an Influenza HA transmembrane domain and C Terminus (TMCT), and one or more genes encoding a heterologous antigen, with a promoter operably linked to the Bgag gene and the TMCT genes; preparing a carrier virus using the transfer vector plasmid; and infecting eukaryotic cells to produce the Bgag VLP, wherein the carrier virus is prepared in the absence of a second transfer vector plasmid.
Claim coverage centers on Bgag VLPs that include Influenza HA TMCT together with a heterologous antigen functionally connected to the HA TMCT, and on a production method that uses a transfer vector plasmid encoding Bgag, HA TMCT, and the heterologous antigen, with carrier virus preparation performed without a second transfer vector plasmid before infection of eukaryotic cells to produce the Bgag VLP.
Stated Advantages
The Bgag VLP supports HA/NA functional activity, including hemagglutination and neuraminidase enzymatic activity.
The Bgag VLP morphology and size are described as typically larger than M1 VLPs.
The platform provides higher spike capacity and surface area relative to other VLPs described in the document.
The document describes egg-independent single-cycle manufacturing for production using baculovirus transfer.
The document describes diagnostic/differentiation potential using Bgag (DIVA), including differentiation of infected from vaccinated animals.
Documented Applications
Multi-pathogen, multi-target, multi-subtype and multi-clade influenza coverage from a single Bgag VLP carrying influenza HA and NA components, including quadri-subtype H5/H7/H9/H10 and triple-clade H555 coverage as described in the document.
Use of Bgag VLPs incorporating heterologous target pathogen proteins, including configurations involving Ebola glycoprotein constructs (e.g., Ebola GP-TMCT) as described in the document.
Diagnostic use for DIVA/differentiation of infected from vaccinated animals using Bgag as a diagnostic tool, as described in the document.
Vaccine performance evaluation including reported protective efficacy via challenge studies in ferrets and chicken challenge with survival and reduced viral shedding as described in the document.
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