Development of a Recombinant VSV-Based Vaccine for Lassa Fever
Abstract
Lassa fever (LF) was discovered in 1969 and is named after the town in Nigeria where the first cases occurred. LF disease is severe and sometimes fatal, and it belongs to a group of diseases known as “viral hemorrhagic fevers” that involve multiple organ systems often accompanied by bleeding (hemorrhage). The virus that causes LF is called Lassa virus (LASV). It has been estimated that LASV infects over 300,000 individuals per year across West Africa (including Sierra Leone, Guinea, Liberia, and Nigeria), causing over 3,000 deaths. The proportion of hospitalized people that die from LF ranges from 15% to 50%, but can be as high as 69%. Airline travelers may bring LF to Europe and the USA, which is how the disease is spread outside Africa. In addition to being a naturally acquired infection, there is concern by the US government that LASV could be deliberately misused to make people sick and cause deaths in places outside where LASV infections naturally occur. Importantly, there are different strains of LASV that occur in the different regions of Africa. Some strains of LASV are more widespread than others, while some strains appear to cause more severe disease in laboratory animals than others. We have developed animal models using monkeys that mimics LF caused by different strains of LASV, just like what is seen in humans. This is important because it allows us to test different vaccines and drugs to make sure that they are effective, well before we do advanced testing in people. Currently, there are no licensed vaccines for the prevention of LF, but several experimental vaccines have been developed. These vaccines are made by using non-infectious parts of LASV so that the animal or person vaccinated makes an immune response against real, infectious LASV. In other words, the vaccines contain non-harmful parts of LASV. When the vaccine is injected into an animal or person, the animal or persons’ immune system thinks it is being exposed to real infectious LASV, and the animal or person can then make a protective response against the deadly LASV. While the majority of vaccines that have been developed against LASV have been shown to make a good immune response in laboratory animals, many have failed to fully protect against lethal disease in animals and most have only been tested against one type (strain) of LASV. A number of these vaccines require multiple doses (shots) to be effective. However, a single shot vaccine is preferred, especially in areas in Africa where LASV is found in nature and for future events where terrorists might use LASV as a weapon. In the case of an intentional release of LASV, there would be little time to give a vaccine that requires several shots over several weeks or months. Thus, in most instances a vaccine against LASV is best if given in a single dose. We developed a vaccine that uses a non-harmful virus called recombinant vesicular stomatitis virus (rVSV) as a way to engineer the vaccine. We made the rVSV vaccine to contain and deliver non-harmful parts of LASV to generate a good immune response against real, infectious LASV. We previously showed that a single shot of this rVSV-based LF vaccine was able to completely prevent monkeys from dying if they were exposed to LASV at a dose that is normally lethal. The vaccine is called rVSV-LASVGPC. Very recently, we performed another study in monkeys and showed that the rVSV-LASVGPC vaccine also protected all the monkeys from death by a very different strain of LASV. This is important because it shows that the rVSV-LASVGPC vaccine can protect against different types of LASV. One important consideration is that all past monkey studies were conducted when the animals were exposed to LASV 28 days after vaccination, but it is not known whether the rVSV-LASVGPC vaccine will still work if animals are exposed to LASV shortly after vaccination or a long time after vaccination. The main objective of our research is to develop a rVS
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910027
Entities
People
- Thomas W Geisbert
Organizations
- United States Army
- University of Texas Medical Branch