There is currently no vaccine for the Lassa arenavirus, which causes Lassa fever. This hemorrhagic fever, endemic in West Africa, infects up to 300,000 people each year. Given the urgency of the situation, scientists in the Biology of Viral Emerging Infections Unit and the Viral Genomics and Vaccination Unit at the Institut Pasteur 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. This raises hopes in the fight against a disease that claims between 5,000 and 6,000 lives every year.
Lassa fever, a hemorrhagic fever caused by the Lassa virus (LASV), is responsible for several thousands of deaths in endemic countries in West Africa every year. The natural reservoir of the virus is a peridomestic rodent that lives near or inside homes, so contacts between humans and the infected reservoir in villages are frequent (see our disease fact sheet). Humans are generally infected by ingesting or inhaling material contaminated with the animal's excreta (urine or feces). 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. The results of their research were published in the journal Science Translational Medicine on October 2.
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.
Vaccines inducing immunity to Lassa virus glycoprotein and nucleoprotein protect macaques after a single shot, Science Translational Medicine, 2 octobre 2019
Mathieu Mateo1,2, Stéphanie Reynard1,2, Xavier Carnec1,2, Alexandra Journeaux1,2, Nicolas Baillet1,2, Justine Schaeffer1,2, Caroline Picard1,2, Catherine Legras-Lachuer3, Richard Allan3, Emeline Perthame4, Kenzo-Hugo Hillion4, Natalia Pietrosemoli4, Marie-Agnès Dillies4, Laura Barrot5, Audrey Vallve5, Stéphane Barron5, Lyne Fellmann6, Jean-Charles Gaillard7, Jean Armengaud7, Caroline Carbonnelle5, Hervé Raoul5, Frédéric Tangy8, and Sylvain Baize1 ,2
1 Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Lyon, France
2 Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, CNRS UMR5308, Lyon, France
3 ViroScan3D SAS, Trévoux, France
4 Bioinformatics and Biostatistics Hub – Department of Computational Biology, USR 3756 CNRS, Institut Pasteur, Paris, France
5 Laboratoire P4 INSERM – Jean Mérieux, INSERM US003, Lyon, France
6 SILABE, Université de Strasbourg, fort Foch, Niederhausbergen, France
7 Laboratoire Innovations Technologiques pour la Détection et le Diagnostic (LI2D), Service de Pharmacologie et Immunoanalyse (SPI), Commissariat à l’Energie Atomique, Bagnols-sur-Cèze, France
8 Viral Genomics and Vaccination, Institut Pasteur, CNRS UMR-3569, Paris, France
This study is part of the Vaccinology and Immunotherapy Initiative of the Institut Pasteur's strategic plan for 2019-2023.