Location: Zoonotic and Emerging Disease Research
Project Number: 3022-32000-027-021-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Aug 15, 2024
End Date: Aug 14, 2026
Objective:
The objective of this proposal are to develop and evaluate the immunogenicity of a virus like particle vaccine for Nipah virus.
Approach:
Nipah virus (NiV) is a zoonotic paramyxovirus of the genus Henipavirus, an emerging pandemic threat. NiV and closely related Hendra viruses (HeV) are highly pathogenic bat-borne paramyxoviruses recently included in the WHO Blueprint priority diseases list. Past NiV outbreaks causing human disease were a result of zoonotic exposure to the natural reservoir, fruit bats of the Pteropodidae family (flying foxes), and found across Oceania, Asia, and Africa. Contact with infected pigs, bat saliva or urine on fruit trees, consumption of contaminated fruits and raw date palm juice, contact with horses or consumption of horse meat or human-to-human contact led to infection in humans.
Vaccination remains the most effective way for control, prevention, and eradication of infectious diseases with pandemic potential. Complimentary to this, plant biopharming is recognized for its scalability, speed, versatility, and low production costs and is an increasingly promising molecular pharming platform for human vaccines. The feasibility of the plant transient expression system to rapidly manufacture clinical grade vaccines and biotherapeutics in response to pandemic outbreaks and biosecurity (sponsored by the Defense Advanced Research Projects Agency, DARPA, Blue Angel Project), was successfully demonstrated in the past. One of the grantees demonstrated that more than 10 million doses of influenza H1N1 virus-like particle (VLP) vaccines could be produced in 1 month. Since then, drug developers have overcome many of the technical and regulatory concerns that plant-based protein expression for target vaccines and biotherapeutics posed before. Recently, Medicago and GlaxoSmithKline (GSK) gained approval from Health Canada for Covifenz®, the companies’ plant-based COVID-19 VLP vaccine. Molecular farming can be established in various settings with minimal cold-chain requirements and could thus ensure rapid and global-scale deployment of biopharmaceuticals, promoting equitable access to pharmaceuticals.
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. The team already successfully assembled VLPs of members of the Paramyxoviridae family i.e. pigeon paramyxovirus and Newcastle disease (ND) VLPs. Nipah virus (NiV) is also a paramyxovirus. NiV-G is considered to bind to the ephrin-B2/B3 receptor, whilst NiV-F drives membrane fusion for viral entry and therefore NiV-G is considered the major determinant glycoprotein. Nevertheless, the efficacy of the minimal structural proteins, including the Fusion-protein and Matrix protein to successfully assemble VLPs in plant and yeast cell factories will be assessed.
Well established platforms are pivotal to pandemic preparedness for Nipah disease outbreaks of human disease that might emerge in the future. We hypothesize that an efficacious plant produced NiV VLP, antigenically matched to a strain of concern will elicit the known correlates of protection in pigs.
