Zoonotic disease Nipah virus (NiV) killed more than 100 people in a 1999 Malaysian outbreak. Simon Graham outlines his work to establish an international consortium that aims to develop a dual purpose (bivalent) vaccine for pigs.
Nipah virus can have devastating consequences for both humans and animals. Carried by fruit bats, NiV can infect pigs and then be transferred to humans, where it can cause encephalitis (brain inflammation), leading to severe illness or even death. The only current way of controlling an outbreak is through animal culling. During the Malaysian outbreak, almost half the nation’s pig population had to be destroyed, devastating a rural economy.
Despite the continued threat of NiV, commercial development of a vaccine is limited: companies understandably fear limited marketability due to the sporadic occurrence of outbreaks. To address this gap, The Pirbright Institute is bringing together an international consortium of scientists and commercial partners to develop a vaccine and companion diagnostic test for NiV infection in pigs.
Together, a two-year, £1.5 million project has been established, funded by the Department of Health and Social Care (DHSC) as part of the UK Vaccine Network (UKVN) – a UK aid programme to develop vaccines for diseases with epidemic potential in low- and middle- income countries (LMICs).
We have teamed up with the Friedrich- Loeffler-Institut (FLI) in Germany and three leading UK companies – EnsiliTech, Global Access Diagnostics and BioVacc Consulting – to create the first-ever bivalent NiV vaccine that could be routinely used to protect pigs against NiV and reduce the risk of future outbreaks.
The project builds on FLI’s expertise in genetic engineering of pseudorabies virus (PrV) which should allow us to develop a vaccine that can provide immunity after a single immunisation. Since live attenuated PrV vaccines are widely used to immunise pigs against Aujeszky’s disease across Asia, the new vaccine could be readily implemented as a bivalent vaccine.
The consortium’s UK partners bring a range of commercial skills and expertise to vaccine Credit: Diego San development. EnsiliTech specialises in biologicals without refrigeration, allowing a silica-coated vaccine to be stored and transported in tropical regions without cold storage; Global Access Diagnostics develop innovative rapid lateral flow immunoassay tests – and will develop a companion diagnostic test that will discriminate infected from vaccinated pigs; and BioVacc Consulting provides expert insight into veterinary vaccine research and development.
We are confident the consortium will be able to make significant progress: the partnership builds on a previous study which developed a two-shot immunisation regime to provide a high level of protection against NiV. And the three UK companies bring unique expertise. For instance, the majority of today’s vaccines require constant refrigeration to ensure efficacy, which may not be available in remote rural regions with limited infrastructure. EnsiliTech’s novel technology, ensilication, could make vaccines thermally stable, removing the need for the cold-chain altogether.
With our bivalent vaccine, we aim to prevent a repeat of the first NiV outbreak caused by transmission from pigs to humans, which brought major economic losses and long-term damage to the Malaysian pig industry
Live attenuated PrV vaccines are highly effective and have been used for successful eradication of pseudorabies from domestic pigs in many countries. These vaccines can be engineered to express antigens from other pathogens. We previously constructed and tested a PrV vaccine that produced both the NiV F and G glycoproteins in a soluble form.
The NiV neutralising antibody response stimulated by prime-boost vaccination was comparable to those seen with protective vaccine candidates. The inclusion of the NiV proteins into the PrV vaccine did not hinder PrV-specific immune responses. Overall, the data suggested that the bivalent PrV-NiV vaccine candidate would likely provide protection against both viruses. However, the immune responses suggest that two doses may be required. The new project will improve the combined PrV-NiV vaccine to provide protection after a single shot by engineering NiV glycoproteins to be expressed on the surface of infected cells and PrV particles, thereby enhancing antibody responses. A ‘one shot’ solution is paramount for its practicability. We will compare the new and original vaccine to determine whether we have improved immunogenicity, and the best candidate will then be tested for its ability to protect pigs against both PrV and NiV infections.
Since NiV infection restricts the ability of countries to trade pigs or pig products, it is essential that any NiV vaccine has a companion test that enables the discrimination of infected from vaccinated pigs. We have already established a lab-based assay that allows such discrimination, and we are working to translate it into a rapid ‘penside’ test that can used in the field.
The lessons of history show us that simple, practical, field-based solutions work best. Human NiV infections have been reported from Malaysia, Singapore, the Philippines, Bangladesh and India, and serological evidence for NiV circulation in bats in Vietnam and Thailand has been published.
With our bivalent vaccine, we aim to prevent a repeat of the first NiV outbreak caused by transmission from pigs to humans, which brought major economic losses and long-term damage to the Malaysian pig industry. Such a vaccine would reduce the major risk NiV poses to both developing pig industries and the livelihoods of poor livestock keepers in LMICs.
Professor Simon Graham is group leader, porcine reproductive and respiratory syndrome (PRRS) immunology, at The Pirbright Institute
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This research is funded by the Department of Health and Social Care using UK Aid funding and is managed by Innovate UK. The views expressed in this publication are those of the author(s) and not necessarily those of the Department of Health and Social Care
