posted on 03/04/2021 06:00
Brazilian scientist Paulo Verardi is a professor of pathobiology and veterinary sciences at the North American University of Connecticut (Uconn). In the summer of 2015, he was visiting his family in Brazil, when the Zika outbreak began to spread, reaching epidemic status. Back in the United States, Verardi called then-doctoral student Brittany Jasperse into her office and told her that she wanted to apply her newly developed vaccine platform to work on an immunizer for the disease-causing virus. Scientific Reports magazine, an article describing the success of the substance in pre-clinical studies with animals.
Modern advances in genomic technology have accelerated the vaccine development process. In the past, researchers needed to have access to the real virus. Currently, just obtaining the genetic sequence of the microorganism can be sufficient to arrive at an immunizer, as was the case with vaccines against covid-19 approved for emergency use and the substance described for Zika by Verardi and Japerse. The duo has already applied for a provisional patent for the new technology.
Using the Zika genetic sequence, Verardi and Jasperse developed and tested several candidate vaccines, which would create virus-like particles (VLPs). It is an attractive approach because the fragments resemble native viruses and, therefore, activate the immune system to mount a defense comparable to what would occur during a natural infection. The important thing is that VLPs have no genetic material and are unable to replicate, that is, they are safe.
The vaccine developed by the two scientists is based on a viral vector, the vaccinia virus, which they modified to express a part of the Zika genetic sequence and thus produce particles similar to it. The immunizer has an additional safety feature: although it is able to replicate in the body, which would be dangerous, this process normally occurs in cell culture in the laboratory. “Essentially, we have included an on / off button”, synthesizes Jasperse. “We can turn on the viral vector in the laboratory when we are producing it, simply by adding a chemical inducer, and we can turn it off when it is being administered as a vaccine, to increase safety.”
The team developed five vaccine candidates in the laboratory with different mutations in a genetic sequence that acts as a signal to secrete proteins. The scientists evaluated how these mutations affected the expression and formation of Zika VLPs and then selected the candidate substance that had the highest particle expression to test in a mouse model of the pathogenesis of the Zika virus.
Verardi and Jasperse found that mice that received a single dose of the vaccine developed a strong immune response and were completely protected from Zika infection. Scientists found no evidence of the virus in the blood of infected mice, who were exposed to the virus after immunization.
Zika is part of a viral group known as flavivirus, which includes the causes of dengue, yellow fever and West Nile fever. The findings of Verardi and Jasperse – in particular, the mutations they have identified that increase the expression of Zika’s VLPs – may be useful in improving the production of vaccines against these diseases, the scientists said.
The ongoing work at the Verardi laboratory incorporates these new mutations in candidate vaccines against other viruses, including Powassan, a tick-borne flavivirus that can cause fatal encephalitis. The Brazilian emphasizes that the development of viral immunizers – in this case, for Zika – helps the world to better prepare for new and emerging outbreaks, through the implementation of structures for vaccine development. “The emerging viruses are not going to stop appearing anytime soon, so we need to be prepared,” says Verardi. “Part of the preparation is to continue the development of these platforms.”
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