Antiviral InteliStrat Inc.

Recombinant, virus vector-based vaccines developed as both prophylactic and therapeutic vaccine against EBV infection and malignancies;

Represents a combination of VLP vaccines that can be administered together to elicit EBV-specific neutralizing antibody and T-cell responses in animal models;

The gH/gL-EBNA1 VLP vaccine is based on sponsor's Newcastle Disease Virus (NDV) virus-like particle (VLP) platform (McGinnes LW and Morrison TG., 2013) that consists of NDV modified as a vector to co-express on the VLP surface recombinant EBV envelope glycoproteins gH and gL that are required together to assure gL transport to the cell surface and formation of a stable cell surface gH/gL complex needed to mediate EBV entry into both epithelial and B cells, along with intracellular latency protein EBNA1 packaged inside the VLPs;
For efficient expression, the construct was realized as follows: the gH ectodomain was fused to the NDV fusion (F) protein transmembrane (TM)/cytoplasmic (CT) domains, while the gL ectodomain was fused to NDV hemagglutinin-neuraminidase protein TM/CT domains;
A truncated form of EBNA1 (Gly-Ala region removed), fused to full-length NDV nucleocapsid protein (NP), was used in the construct to allow proper cytotoxic T-cell recognition;

The  gB-LMP2 VLP vaccine is similarly based on the NDV VLP platform with the EBV gB envelope glycoprotein, involved in fusion with epithelial cells, expressed on the VLP surface while intracellular latent membrane protein 2 (LMP2) is packaged inside the VLPs;
For efficient expression, the construct was realized as follows: the gB ectodomain was fused to the NDV fusion (F) protein TM/CT domains, and the full-length LMP2 sequence was fused to NDV NP;

The gp350/220-EBNA1 vaccine is similarly designed, with the EBV gp350/220 surface glycoprotein fused to the NDV fusion (F) protein TM/CT domains, and the truncated EBNA1 sequences fused to full-length NDV nucleocapsid protein (NP);

All cDNA sequences encoding EBV surface glycoproteins and latent membrane proteins are derived from the B95-8 virus strain, and the different vaccine VLPs are produced in Chinese hamster ovary (CHO) cells;

All three vaccine candidates induced neutralizing Abs and generated EBNA1- or LMP2-specific T-cells in immunized wild-type BALB/c mice


Ref.: Perez EM et al., Oncotarget. 2017 Mar 21;8(12):19255-19273 [pubmed.ncbi.nlm.nih.gov/27926486]; McGinnes LW and Morrison TG., Curr Protoc Microbiol. 2013 Oct 2:30:18.2.1-18.2.21 [pubmed.ncbi.nlm.nih.gov/24510891]; Ogembo JG et al., J Transl Med. 2015 Feb 6:13:50 [pubmed.ncbi.nlm.nih.gov/25885535]; Zhong L et al., NPJ Vaccines. 2022 Dec 9;7(1):159 [pubmed.ncbi.nlm.nih.gov/36494369]