Development of Recombinant Viral Vaccines for HFRS-Causing Hantaviruses
Abstract
This proposal addresses two of the “Areas of Encouragement” within the Topic Area “Vaccine Development for Infectious Diseases”: (1) Development and fielding of vaccines to prevent Service members from becoming ill from endemic disease exposure during operational deployments – hantavirus hemorrhagic fever with renal/pulmonary syndrome and (2) development of flexible vaccine technologies that can be used to rapidly respond to emerging and re-emerging infectious diseases threats. Hemorrhagic fever with renal syndrome (HFRS) is an often deadly disease that is caused by a several species of widely distributed (throughout Eurasia) Old World hantaviruses that are maintained in rodent reservoirs and are spread by inhalation of rodent excreta. Most prominent are Hantaan (HTNV) and Seoul (SEOV) viruses in Asia and Puumala (PUUV) virus in Europe. Worldwide it is estimated that between 60,000 and 100,000 cases occur annually with a small percentage of these cases resulting in death. As a starting point for an effective vaccine against these HFRS-causing viruses, we will use a different, nonpathogenic virus, vesicular stomatitis virus (VSV), to express a protein from HTNV or PUUV by producing a recombinant VSV (rVSV). A similarly genetically modified VSV that expresses a protein from the Ebola virus is currently being used to combat Ebola in Africa. Additionally, other rVSV targeting other viral infections are showing promise in animal testing. Because of the success of the Ebola vaccine, there is currently great interest in developing additional rVSV vaccines. Although the VSV virus does normally cause disease in humans and the genetically altered vaccine rVSVs tested thus far also appear safe in normal animals, when VSV itself or some rVSVs enter the central nervous system or are used to infect animals that have immune deficiencies, severe disease or death can result. Due to the concerns raised by these findings, we are also engineering rVSVs that are designed to be safer and less likely to cause disease even if they enter the central nervous system or infect a severely immunocompromised individual.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910137
Entities
People
- Paul Bates
Organizations
- United States Army
- University of Pennsylvania