Lassa fever: All set for Vaccine trial

There is currently no vaccine for the Lassa arenavirus, which causes Lassa fever. Lassa fever, a hemorrhagic fever caused by the Lassa virus (LASV infects up to 300,000 people each year.

Scientists in the Biology of Viral Emerging Infections Unit and the Viral Genomics and Vaccination Unit at the Institut Pasteur sensing the urgency of the situation evaluated the efficacy of several vaccine candidates. Following their analyses, they identified one of these vaccines, based on the measles platform, as being the most effective to enter clinical testing in humans as soon as possible. The results of their research were published in the journal Science Translational Medicine.

Early diagnosis of Lassa fever is difficult to establish because the first symptoms are non-specific (fever, vomiting and nausea), and there is currently no treatment. Vaccinating the populations concerned is, therefore, the most promising strategy to deal with recurrent outbreaks of Lassa fever. The World Health Organization (WHO) has included Lassa fever in its R&D Blueprint list of epidemic threats needing urgent R&D action.

Frédéric Tangy, Head of the Institut Pasteur's Viral Genomics and Vaccination Unit, said in an interview: "When it comes to vaccines, all the easy work has already been done, and the more difficult work has still not been completed. Fundamental research is vital for the development of new solutions."

To address this public health challenge, Institut Pasteur scientists have therefore developed and tested several vaccines.

Two vaccine candidates to tackle Lassa fever

"The aim of this study was to identify the best potential vaccine for Lassa fever. We wanted a vaccine that would offer protection after a single injection so that it could be used in the urgent context of an outbreak," explains Mathieu Matéo, a scientist in the Institut Pasteur's Biology of Viral Emerging Infections Unit and lead author of the study.

The scientists used two vaccine platforms based on live attenuated viruses that had been modified to express LASV antigens: a recombinant measles vaccine strain developed by Frédéric Tangy, Head of the Institut Pasteur's Viral Genomics and Vaccination Unit, which had already produced very positive results in clinical trials for chikungunya; and a recombinant Mopeia virus, closely related to the Lassa virus but not pathogenic for humans, that was genetically hyperattenuated by the scientists.

"We compared the efficacy of these vaccines in preventing LASV infection in a preclinical animal model. The vaccines were well tolerated and induced protection against Lassa fever after a single shot, but with different levels of efficacy," continues Mathieu Matéo. A comparison of immune responses after infection demonstrated that the best protection was associated with early T and B cell immune responses directed against several Lassa virus proteins. Analyses carried out on samples taken after vaccination also suggest that early induction of innate immunity and activation of immune T cells from just two days after immunization correlates with efficient protection.

"The most effective vaccine, the one based on the measles vaccine platform expressing LASV antigens, was recently selected by the CEPI (Coalition for Epidemic Preparedness Innovations) to enter clinical trials in humans by the end of the year," concludes Sylvain Baize, Head of the Biology of Viral Emerging Infections Unit and last author of the study.