Location: Zoonotic and Emerging Disease Research
Project Number: 3022-32000-027-018-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Aug 1, 2024
End Date: Aug 1, 2025
Objective:
The objective of this project is to develop and test a safe and efficacious Nipah virus like particle vaccine.
Approach:
Virus-like particle (VLP) vaccines are non-replicating multiprotein shells similar in size and shape to the intact virus but lack the viral genome and are therefore non-infectious. VLPs are free from live virus yet are highly immunogenic as they display epitopes in a dense and repetitive array similar to a live virus. We hypothesize that an efficacious plant produced NiV VLP (Fig. 1), antigenically matched to a strain of concern will elicit the known correlates of protection in pigs as an animal model.
The aim of the study is to transiently express and assemble NiV VLPs in plant leaf tissue (and yeast as an alternative expression platform) as a vaccine product using a prefusion-stabilized Fusion protein (pre-F), Glycoprotein (G) and matrix (M) structural proteins. CLPs presenting key NiV epitopes will be assembled as a potential booster vaccine. These products will be evaluated as a potential vaccine in preclinical studies in pigs to protect against NiV.
Milestone 1 (Year 1) Assembly of Nipah VLPs and CLP-NiV epitopes as vaccine products
Objective 1:
1a to design, synthesise, clone, express and assemble NiV-G/F and M VLPs in plant leaf tissue;
1b to display 5 independent NiV epitopes using a CLP display platform in plant leaf tissue;
1c to clone relevant gene sequences in selected constructs for yeast expression;
1d Compare yield of plant and yeast cell factories for optimal assembly of VLPs;
1e to define downstream purification processes (DSP) for plant and yeast expression platforms.
Milestone 2 (Year 2) Production and characterisation of NiV VLPs and CLP vaccine products for pig study with the focus on correlates of protection including neutralizing antibodies and cell-mediated responses. Tailoring appropriate adjuvants.
Objective 2:
2a to produce NiV VLPs and CLPs;
2b to fully characterise the vaccine products including glycosylation patterns and potential cytotoxicity;
2c to validate the vaccine products in pigs as an animal model.
