Active Infection & Immunity Genetics & Molecular Biology

DNA-launched Nipah virus vaccines and therapeutics

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Nipah virus has no vaccines or treatments, and a UK research team is now testing a DNA-based platform to change that. The virus kills people and livestock across Southeast Asia, yet no licensed vaccines or therapies exist. The team has already developed an injectable DNA delivery system—using polymer and peptide nanoformulations—that proved effective for a Zika vaccine in animal models. They now aim to adapt this same platform for Nipah. The researchers will isolate new therapeutic antibodies from human volunteers in Malaysia who recovered from Nipah infection, then test both DNA-encoded vaccines and antibody candidates in mice, pigs, and hamsters. They will also compare standard plasmid DNA with a synthetic DNA system that could enable single-dose efficacy and faster manufacturing. If successful, the work could produce affordable, stable, and scalable vaccines and treatments for both humans and livestock. That would give outbreak responders a practical tool to contain Nipah in affected regions, potentially preventing the virus from spreading through animals and into people.

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Background: Despite the significant threat Nipah virus poses to both human and animal populations across Southeast Asia, neither vaccines nor therapeutics are currently available to prevent or treat infection. If the delivery challenge could be overcome, DNA-launched approaches have advantages over other platforms (including mRNA) for vaccines and therapeutics, such as low production cost, time-to-impact, and enhanced stability for transportation/storage. We have generated an injectable DNA vaccine platform which we are exemplifying as a Zika vaccine (IUK, SBRI funding), which is currently being tested in mouse and non-human primate models. Translating the gains of the effective delivery system with DNA-encoded antigens or therapeutics would be transformative for tackling Nipah virus. Study aims: We propose to exploit our recently established DNA-delivery platform to advance the development of effective, affordable, and scalable Nipah virus vaccines and therapeutics. Our platform is based on polymer/peptide nanoformulations that are vectors for DNA delivery. Due to the simplicity of formulation this opens up the possibility of a tractable and deployable method to vaccinate and treat Nipah in a ‘One Health’ approach tackling both human and animal disease. This study aims to generate the pre-clinical efficacy data needed to support the further translation of the approach. The approach: Whilst the protective antigens from the Nipah virus are well defined and could be readily engineered into the DNA vaccine platform, there are a limited number of human monoclonal antibody (mAb)-based therapeutic candidates, with only one in clinical testing. We therefore propose to isolate new therapeutic candidate mAbs from human volunteers in Malaysia, who previously recovered from Nipah virus infection. Both DNA-encoded vaccine and therapeutic mAb candidates will be evaluated in preclinical animal models. After initial optimisation using a mouse model, vaccine and therapeutic candidates will be assessed evaluated for immunogenicity and pharmacokinetics, respectively, in pigs. And their efficacy to protect against Nipah virus infection will be tested in hamsters. We will also compare plasmid and synthetic DNA systems (dbDNA) which will improve low and single-dose efficacy, with more rapid and deployable manufacture. Outputs: The major gain here is the discovery and preclinical testing of DNA encoded Nipah virus vaccine and therapeutic candidates, supporting their further clinical development. Furthermore, the livestock testing of the platform could be transformative as a route as an agricultural vaccine, which could prevent and contain Nipah virus outbreaks in affected areas of Southeast Asia

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Researchers

James Dixon (Co-Investigator)Li Yen Chang (Co-Investigator)Simon Graham (Principal Investigator)Won Fen Wong (Co-Investigator)

Related Research

Grants with similar aims, by meaning.

Development of a Next-Generation, Dual-Target Rabies/Flavivirus Infectious DNA (iDNA) Vaccine
Development of a Nipah model of disease
A Nipah vaccine to eliminate porcine reservoirs and safeguard human health
A live attenuated pseudorabies virus vectored Nipah vaccine for enhanced protection in pigs
DNA-based delivery of antiviral antibodies for Zika and Influenza prevention

Original classification

Research and Innovation

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