Most emerging infectious diseases affecting humans in the last century have originated in animal reservoirs and are defined as zoonotic. Lassa fever is a significant zoonotic disease threat to human health in West Africa with an estimated 100,000 to 300,000 cases of disease each year, of which about 5,000 are fatal1.
In a recently completed grant-funded project with global partners, it was shown that Lassa fever virus is circulating in mastomys rat populations in West Africa. A species-specific cytomegalovirus (CMV) was isolated and shown to be widespread in these populations2. One of these CMV strains was selected for use as a viral vector to carry Lassa fever virus protective antigens for a Lassa fever vaccine. In controlled studies under Category 4 Biosecurity the vaccine was shown to be immunogenic in inoculated animals, transmissible to naïve co-housed cagemates (essential for a wild-life vaccine) and was shown to reduce Lassa fever virus infection and excretion after challenge.
In anticipation of the successful demonstration of proof-of-principle for this Lassa fever vaccine candidate for use in the reservoir of infection for Lassa fever virus in West Africa, TVG made global patent filings in 2019 and 2020 to protect this invention. We now have a first positive opinion in the UK and expect the patent to be granted imminently. The granted claims cover the ability of the vaccine to achieve the necessary level of Lassa virus immunity before gradually losing the Lassa virus gene, which restores the vaccine to naturally occurring wild type CMV already present in the wild-life populations. A second product-specific patent was also filed subsequently in the UK in December 2022 and is under review currently.
Currently an extended clinical programme is ongoing within a captively bred mastomys rat colony under BSL 4 high level biosecurity conditions. These studies aim to demonstrate the protection provided by the transmitted vaccine, and reduction in Lassa fever carriage upon challenge. Future work will use the vaccine challenge study data to refine the computer model developed to predict the outcomes of Lassa fever control interventions. Continued engagement with stakeholders with an interest in the control of Lassa fever in West Africa, such as the Wellcome Foundation and WHO, will be important to identify the environment in which the tools developed by this project can be deployed. TVG is in discussion with a vaccine manufacturer in West Africa for transfer of the required vaccine and production cell line technologies.
Jeremy Salt, TVG Chief Executive Officer, said: “The original Darpa-funded project delivered a range of tools for use potentially as part of a future control programme for Lassa fever in West Africa. The vaccine candidate developed can play a vital role in controlling Lassa fever virus circulation in the reservoir host populations in West African countries. Ongoing contained clinical studies should deliver the efficacy data that we need to take this vaccine forward into controlled field studies eventually. Liaison with public health bodies to deploy this tool in integrated Lassa fever control programmes in future is essential to make inroads into the reduction of risk of further zoonotic infection of humans. ”