The Vaccine Group, a University of Plymouth spinout company, has successfully completed a project to develop a transmissible vaccine for use in the rats that spread Lassa fever and to reduce its threat to humans.
A small-scale trial of a candidate vaccine in controlled conditions has shown it could be transmitted between rats and significantly improve their immunity to the disease. Technology has also been developed that has the potential to scale up the vaccine for commercial production.
The work, led by University of California, Davis, was funded by the US Defense Advanced Project Research Agency (DARPA) and saw scientists at The Vaccine Group collaborating with academic partners from around the world.
Their work confirmed Lassa fever virus to be circulating in mastomys rat populations in West Africa, and isolated a species-specific cytomegalovirus (CMV) found to be widespread in these populations.
The isolated CMV strains were down-selected based upon growth parameters in vitro, and a candidate vector strain was selected for use as a viral vector for the vaccine candidate.
Two potentially protective antigens were identified from Lassa fever virus, and a lead candidate was selected with a transgene inserted into a single site in the CMV vaccine vector. In addition, a continuous cell line with the potential for commercial scale production of the vaccine was developed from mastomys rat tissues.
A small-scale trial batch of the candidate vaccine was used in controlled studies under biosecurity containment and shown to be immunogenic in inoculated animals and transmissible to naïve co-housed cagemates.
The vaccine was also shown to reduce Lassa fever virus infection and excretion after challenge at highly significant levels. In addition, the vaccine is constructed 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 animals.
