Brazilian scientist Paulo Verardi professor of pathobiology and veterinary science 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 the status of epidemic. Back in the United States, Verardi then called 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 preclinical studies, with animals.
Modern advances in genetic technology have accelerated the vaccine development process. In the past, researchers needed access to the real virus. Currently, only obtaining the genetic sequence of the microorganism can be enough 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 genetic sequence of Zika, Verardi and Jasperse developed and tested several candidate vaccines, which would create virus-like particles (VLPs). This 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 do not have genetic material and are unable to replicate, that is, they are safe.
The vaccine developed by the two scientists based on a viral vector, the vaccinia virus, which they modified to express part of the sequestration genetics of Zika and thus produce particles similar to it. The immunizer has an additional safety feature: although, in the body, it is able to replicate, which would be dangerous, this process normally occurs in cell culture in the laboratory. “Essentially, we include an on / off button,” synthesizes Jasperse. “We can turn on the viral vector in the lab 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 laboratory with different mutations in a genetic sequence that acts as a signal to secrete proteins. The scientists assessed how these mutations affected Zika expression and VLP formation, and then selected the candidate substance that had the highest express of particles to test in a mouse model of Zika virus pathogenesis.
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 the infected mice, which were exposed to the virus after immunization.
Zika is part of a viral group known as flavivrus, 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 vaccine candidates against other viruses, including Powassan, a flavivirus transmitted by ticks that can cause fatal encephalitis. The Brazilian emphasizes that the development of viral immunizers – in this case, for Zika – helps the world better prepare for new and emerging outbreaks, through the implementation of structures for vaccine development. “The emerging viruses will not stop appearing so soon, so we need to be prepared,” says Verardi. “Part of the preparation to continue the development of these platforms.”
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