Development of Novel Vaccination Approaches for New World Hantaviruses

Hantaviruses are a group of zoonotic viruses carried by a wide range of different species, including mice, rats, voles, shrews, moles, and bats. Most hantaviruses known to cause disease in humans are found in rodents and infection occurs through inhalation of the virus found in rodent excreta or secreta. Depending on location, hantaviruses can cause two distinct diseases, though there is some overlap in symptoms and disease manifestations. In Europe and Asia, hantaviruses cause hemorrhagic fever with renal syndrome, a disease primarily impacting the kidneys. In the Americas, they cause hantavirus cardiopulmonary syndrome (HCPS). HCPS is a severe respiratory disease that can have a case fatality rate of up to 40%. Critically there are no approved vaccines or treatments for HCPS. This project aims to design and develop vaccines that can prevent HCPS in hantavirus exposed individuals. We have recently developed 3 different vaccine approaches to test in preclinical animal models, against Andes virus and Sin Nombre virus, two key hantaviruses found in South and North America, respectively. One of these is a classic protein subunit-based vaccine. One is a protein-liposome based approach based on fusion of the viral proteins to an immunogenic liposome carrier. And the last is a viral-vectored vaccine based on Newcastle Disease virus, an approach that has been used previously for several vaccines and approved for use in humans for COVID-19. Our preliminary data has shown that we can produce these vaccines and they can induce strong immune responses in mice and hamsters. Ongoing studies will determine protection of each vaccine against HCPS using the Syrian hamster model of infection, representing the only small animal model of hantavirus disease. This work will advance our understanding of hantavirus vaccine-mediated protection and lay the foundation for future vaccine development and approval for hantaviruses.