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Promise of Synthetic Biology for Covid-19 Vaccine

Reporter: Irina Robu, PhD

Researchers and epidemiologists’ race to develop vaccines to block the new Covid-19 pathogen that currently emerged. It’s a rush against the clock, and sometimes the good guys lose: It simply takes too long to identify an effective antigen and produce enough of it to make a dent.

Even as companies rush to advance and test vaccines against the new coronavirus, the Bill and Melinda Gates Foundation and the National Institutes of Health are gambling that scientists can do even better than what’s now in the pipeline. The traditional vaccine-development development is decades old. It involves shipping a sample of the purified virus to a vaccine-development laboratory, developing a nonpathogenic variant of the virus, propagating that new variant in eggs or cultured cells and harvesting them to produce the vaccine.

To develop a coronavirus vaccine, synthetic biologists are currently racing against the clock. It is quite possible that the new Covid-19 virus will become a permanent part of the world’s microbial menagerie rather than being eradicated like the earlier SARS coronavirus, next-gen approaches will be needed to address inadequacies of even the most cutting-edge vaccines: They take years to develop and manufacture, they become obsolete if the virus evolves, and the immune response they produce is often weak.

Neil King, a researcher from University of Washington has been hunting for a coronavirus vaccine since 2017, because he knew that would be another coronavirus epidemic similar to SARS and MERS. His group designed and built nanoparticles out of proteins and attach viral molecules in a repetitive array with the intention of, when the whole thing is packed into a vaccine, it can make people resistant to the new coronavirus. Using computers, they are designing new, self-assembling protein nanoparticles scattered with antigens. If tests in lab animals of the first such nanoparticle vaccine are any indication, it should be more potent than either old-fashioned viral vaccines like those for influenza or the viral antigens on their own (without the nanoparticle).

King and his colleagues (Cell, 2019) developed an experimental vaccine against respiratory syncytial virus (RSV) made of a computer-designed nanoparticle that self-assembles from protein building blocks and is scattered with an engineered version of RSV’s key antigen. When tested in mice and monkeys, it produced 10 times more antibodies than an experimental RSV vaccine based on traditional technology. They believe that with a few tweaks, the nanoparticle can be scattered with molecules from additional coronaviruses such as the original SARS virus, MERS, and a mutated form of the Covid-19-causing virus. As Covid-19 spreads, King and his colleagues are carefully optimistic that it might work.

But even though, Moderna Terapeutics, CureVac and Inovio pharmaceuticals are speeding toward human testing via experimental vaccines that contain synthetic strands of RNA or DNA, the synthetic biology approach has its own advantages. These experimental vaccines contain synthetic strands of RNA or DNA that code for protein molecules on the virus’s surface. Once the vaccine delivers the genetic material into cells, the cells follow the genetic instructions to churn out the viral protein. The knowledge is that the body would perceive that as foreign, generate antibodies to it, and if all goes well thus acquire immunity to the virus.

Researchers already know how to do vaccine development the old-fashioned way, and their manufacturing facilities are set up accordingly. The regulatory approvals required to produce their vaccines are geared to this older technology, as well, and updating those processes and approvals could take considerable time. So even though, researchers are racing against time to find a solution to Covid-19 virus, synthetic biology has such a vast potential.

SOURCE

To develop a coronavirus vaccine, synthetic biologists try to outdo nature