Flaviviruses – a group of viruses transmitted by ticks or mosquitoes – infect an estimated 400 million people annually with diseases such as yellow fever, dengue fever, West Nile virus and, most recently, the Zika virus.
Outbreaks of the Zika virus, a flavivirus native to Africa, were once rare and isolated events. But it came to America in 2015 and quickly spread to 27 countries within a year.
Outbreaks of the Zika virus have now been recorded throughout Southeast Asia, the South Pacific, South America and Central America. To protect the health of billions of people at risk and prevent future outbreaks, a team of Virginia Tech researchers received a R01 million grant from the National Institutes of Health to create a safe, effective single-dose vaccine candidate for the Zika -Virus to develop.
This grant focuses on a new strategy we have developed to create safe and effective flavivirus vaccines. The aim is to prevent these viruses – in this case the Zika virus – from occurring in humans. “
Jonathan Auguste, Assistant Professor, Department of Entomology, College of Agriculture and Biosciences
Irving Allen, an associate professor, and XJ Meng, a distinguished university professor, both from the Department of Biomedical Sciences and Pathobiology at the Virginia-Maryland College of Veterinary Medicine, join Auguste as co-investigators. With this grant, they will test the safety and effectiveness of this vaccine candidate.
“The Auguste Lab recently developed an exciting and highly innovative vaccine platform that has the potential to revolutionize vaccine development against other flaviviruses that infect humans and other animals. The flaviviruses pose a tremendous burden on public and veterinary health and are therefore evolving effective vaccines against flaviviruses such as the Zika virus will help prevent and control disease outbreaks more effectively, “said Meng, whose expertise is in virology and vaccine.
To develop their vaccine platform, Auguste’s lab isolated a virus from mosquitoes that can only multiply in mosquito cells – meaning it cannot infect mammals. Together with James Weger-Lucarelli of the Institute of Biomedical Sciences and Pathobiology at the Virginia-Maryland College of Veterinary Medicine, they replaced the proteins that code for the behavior of the virus with proteins that make it look like a pathogen. Ultimately, they created a virus that looks identical to the Zika virus, but it cannot replicate itself.
“It has many advantages because it is exceptionally safe – if it cannot replicate it does not cause disease. It cannot acquire mutations that cause disease because its replication is defective. So it grows very well in cell cultures. It is.” easy to produce. With just one vaccination you can get a really good immune response, “said Auguste, who is also a faculty member at the Fralin Life Sciences Institute and the Center for Emerging, Zoonotic, and Arthropod-borne Pathogens.
In vaccine development, there is a tradeoff between safety and immunogenicity, the ability to elicit an immune response. A vaccine against killed viruses is exceptionally safe, but multiple doses can be taken to produce a sufficiently strong immune response to protect the individual. On the other hand, an attenuated live virus vaccine is made from an attenuated form of the virus so that the response it produces is more immunogenic and effective. By combining elements from both vaccine development strategies, Auguste, Allen and Meng developed a platform that safely generates a sufficiently robust immune response with just one dose.
“This project is exciting as it uses a novel strategy to generate and validate a vaccine candidate against Zika that should have the benefits of the live attenuated vaccine and the safety profile of the inactivated vaccine,” said Allen, who will contribute experience of immunology to understand how the vaccine works so effectively.
The team has already had success testing its vaccine platform on mice, showing that it completely protects against replication of the virus in the blood. Their vaccine also treats one of the most serious effects of Zika infection – microcephaly. It occurs when a mother infected with Zika transfers the virus to the fetus, resulting in shrinkage of the baby’s head and poor brain development. But this vaccine platform “completely protected mice from transmitting Zika in the uterus,” Auguste said.
In the next steps in vaccine development, Auguste and his colleagues need to do some preliminary studies and compare their vaccine with other vaccine candidates.
“I look forward to comparing my platform to other platforms that are already in clinical trials. This one-to-one comparison gives me a really good understanding of where this platform can go. If this is a very good platform, it can be used as a The basis for the production of vaccines that you can protect against multiple flaviviruses with just one vaccination, “said Auguste.
If this is a platform worth pursuing, researchers will run tests on higher order animals, such as non-human primates, to ensure the vaccine’s safety and effectiveness. If all goes well, the vaccine will later move into clinical testing.
A treatment or vaccine against the Zika virus and other flaviviruses does not yet exist. With the recent emergence of flaviviruses and the associated public health threat, Auguste and his colleagues are testing whether their vaccine can also protect people from multiple flaviviruses.
“It’s really important in places like the tropics where people go on vacation all the time. For example, in my home country of Trinidad and Tobago, we have yellow fever, Zika and dengue fever on the same island,” he said. “So such a vaccine is not only desirable – it is necessary.”