Caroline Green

Nature: Scientists Are Developing Nanovaccines to Fight Coronavirus

Blog Post created by Caroline Green on Apr 29, 2020

As infections from SARS-CoV-2 spread from Wuhan, China, to all over the world, researchers are scrambling to develop a vaccine and life science companies are providing help.


On January 28, 2020, a few weeks after the first official report of the first case of coronavirus in 2019, the U.S. Department of Health and Human Services held a press conference in Washington, D.C., saying that SARS-CoV-2 infected thousands of people and that millions of people in China were isolated, but there was no way to treat the virus. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), told reporters: "We are considering the worst case scenario, that is, the outbreak is further expanding." To stop the outbreak and save lives, the world needs a vaccine, he said.


Since the severity of the outbreak is unknown, at least five research groups are working to develop a vaccine that uses various strategies to stimulate an effective immune response. However, the development of vaccines may be slow compared to the rate of spread of SARS-CoV-2. Vaccine development took at least six months in cases of Zika virus, Ebola virus, and swine influenza in 2009, which is still hailed as a record rate.


Preclinical and clinical trials require significant time, as does scale-up production and distribution. And it will take a lot of time to develop prototype vaccines. In the past few years, vaccines have often come too late to help contain the initial outbreak. This time, researchers are accelerating and life science companies are becoming key players in the development of SARS-CoV-2 vaccines.


On January 10, the Chinese Center for Disease Control and Prevention released the complete genome sequence of the then unnamed coronavirus to public databases, and the competition for vaccine research and development officially began. This was particularly noted by Genscript, a life science company based in Piscataway, New Jersey.


The company's manufacturing facilities are located in China and the United States and have made it a mission to support the development of the SARS-CoV-2 vaccine; many Chinese scientists have cancelled their holidays to keep the laboratory running 24 hours a day. Less than two weeks after the release of the viral genome sequence, Genscript released a novel SARS-CoV-2 assay for initial screening, and its researchers are responding to the needs of genes, proteins, and peptides from vaccine developers around the world.


To accelerate the development of prototype vaccines, Genscript provides complete genes within a few days. To this end, the company first synthesized thousands of DNA fragments on a set of computer-controlled platinum electrodes on a semiconductor chip, adding one nucleotide to each growth fragment at a time. After they synthesized these fragments or oligonucleotides, they stitched them together using a proprietary technique to produce high-quality long-stranded DNA, which was then cloned and sequenced to verify no errors.


Novavax, a biopharmaceutical company based in Gaithersburg, Maryland, turned to Genscript to accelerate the development of recombinant nanoparticle vaccines. “We're never exposed to viruses,” said Gregory Glenn, president of research and development at the company. “We design the genes we want, and then they make them,” he said.


On January 10, shortly after the complete genome sequence of SARS-CoV-2 went online, Novavax ordered the full-length gene of the S protein of SARS-CoV-2 from Genscript. This syringe-like protein attaches to cells in the respiratory tract and injects them with viral RNA.


Novavax, which is committed to developing the next generation of vaccines for serious infectious diseases, plans to insert the full-length S protein gene into a baculovirus that infects insect cells. When this virus infects laboratory-cultured insect cells, Glenn says, the coronavirus S protein is produced, which is folded and encapsulated in a sugar coat, as if it were produced by human cells.


Novavax will then insert this S protein into micelles, an artificial membrane system the size of viral particles. The micelles show part of a spike protein called an epitope, which has evolved little and is therefore very similar from one coronavirus to another. These antigenic determinants are usually out of reach of the immune system, but in Novavax's vaccine, they are “naked to the world”, Glenn said. For this reason, they trigger an immune response that should target many variants of this S protein and therefore prevent all variants of SARS-CoV-2 that one may encounter.


Even today, building a full-length gene like the S gene still requires high-quality engineering, which is difficult to achieve, and for Novavax, every day is important. Genscript synthesized the full-length gene of SARS-CoV-2 and delivered it at 3. “It's amazing,” says Glenn.


Since then, Novavax has been accelerating the development of the vaccine and will conduct clinical trials before the early summer, Glenn said. Other vaccine developers are moving forward at an extremely rapid rate, using DNA vaccines, messenger RNA vaccines, or a vaccine called molecular clamps to stabilize viral proteins. No one knows which one will win.


Nevertheless, the race to the clinic is still going on because many lives are at stake.