Lassa Viral Transmission and Immunoprotection: Defective Interfering Particles (DIPs) in Carrier Rodents and Lassa Virus-Infected People

The World Health Organization lists Lassa virus (LASV) as one of the of top 10 pathogens with high epidemic potential. LASV is currently endemic to West Africa, infecting up to 500,000 people, annually. It causes Lassa fever (LF) with symptoms ranging from malaise/deafness to haemorrhaging through all orifices. LASV can be as dangerous as Ebola and SARS-CoV-2. About 20% of LASV-infected people develop disease that can severely damage the brain, liver, spleen, kidney and other vital organs. Hospital fatality of LF patients can be as high as 69%. But, the reasons why LASV-infected people mount such varying immune responses are not understood. LASV is transmitted to humans mainly through the aerosols of urine/faeces of rodents. As an RNA virus, it has an inaccurate system of replication. 'Errors' in replication can lead to the production of defective interfering viral particles (DIPs) that are known to modulate immune response, in other RNA viruses. DIPs are present in LASV-infected mice, but their relevance in LF in humans is unknown. Therefore, during my Fellowship, I will determine whether (i) DIP levels vary between rodent species and modify transmissibility to humans, and how (ii) DIPs modulate immune responses in LASV-infected people, and regulate disease severity in LF patients. DIPs will be measured in rodent urine, faeces and tissue to understand how individuals in endemic areas are exposed to Lassa antigens. DIPs and antibodies in the patients' blood will be studied to reveal their role in disease progression and immunity. Because DIPs stimulate immune response without causing infection, DIPs are considered as vaccine candidates (e.g., Ebola, SARS-CoV-2, Dengue, Zika). No satisfactory treatment or vaccine is available to fight against LF. Hence, understanding LASV transmission and immunogenicity via a One Health approach, and identifying novel LASV vaccine candidates and diagnostic approaches are of paramount importance to prevent a LF pandemic.