Development of a Recombinant VSV-Based Vaccine for Nipah Virus
Abstract
Nearly 20 years ago, Nipah virus (NiV) was first isolated and identified as a new virus belonging to the family of paramyxoviruses. Its name originated from Sungai Nipah, a village in the Malaysian Peninsula where pig farmers became ill with brain swelling, known as encephalitis. NiV causes encephalitis and respiratory illness in humans, and is 100% fatal in some outbreaks. Scientists have identified two strains of NiV that occur in different areas, one called the Malaysia strain (abbreviated NiVM) and one called the Bangladesh strain (abbreviated NiVB). The NiVB strain appears to more pathogenic because more people die from an infection with this strain. Fortunately, we have developed an animal model using monkeys that mimics the differences between the NiVM and NiVB strains, 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 NiV disease. Several new experimental vaccines have been developed. These vaccines are made by using non-infectious parts of NiV so that the animal or person vaccinated makes an immune response against real, infectious NiV. In other words, the vaccines contain non-harmful parts of NiV. When they are injected into an animal or person, the animal’s or person’s immune system thinks it is being exposed to real infectious NiV, and the animal or person can then make a protective response against the deadly NiV. While the majority of vaccines that have been developed against NiV have been shown to make a good immune response in laboratory animals, many have failed to fully protect against lethal disease in animals. A number of these vaccines require several doses (shots) to be effective. However, a single-shot vaccine is preferred, especially in areas in Asia where NiV is in nature and for future events where terrorists might use NiV as a weapon. In the case of preventing natural infections, giving several doses of the vaccine is both too costly and not practical in developing countries. In the case of an intentional release of NiV, 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 NiV is best if given in a single dose. Previously, we developed several NiV vaccines that use 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 NiV to generate a good immune response against real, infectious NiV. These vaccines were evaluated 28 days after a one-dose vaccination in ferrets and were shown to keep the ferrets from getting lethal NiV disease. An important consideration with regard to the animal studies conducted to date is that all of the studies used the less deadly NiVM strain and not the deadlier NiVB strain. This is important because we recently showed that a treatment against NiV given to animals that were already infected with NiV worked if the animals were exposed to NiVM, but did not work if the animals were exposed to the more lethal NiVB. Considering these new data, the current vaccines against NiVM need to be tested against the more deadly NiVB strain. To address this concern, we recently used our rVSV-based NiVB vaccines in a new monkey model of NiVB. This new model mimics exactly what is seen in humans, in which more deaths are seen with the NiVB strain. Importantly, a single shot with the rVSV-based NiVB vaccine protected all the monkeys after they were exposed to the deadlier NiVB strain 28 days after vaccination; the vaccine that worked is called rVSV-NiVBG. The main objective of our research is to develop a rVSV-based vaccine against NiV that can give protection quickly that lasts a long time, especially for the deadlier NiVB strain. Importantly, our
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910028
Entities
People
- Thomas W Geisbert
Organizations
- United States Army
- University of Texas Medical Branch