Coronaviruses like SARS-CoV-2, which was identified as the cause of an outbreak of respiratory illness that began in Wuhan, China, are covered with protein spikes, colored red in this illustration, that help them bind to host cells.Credit: Alissa Eckert and Dan Higgins/CDC
On 28 January 2020, just weeks after the first official reports of the 2019 novel coronavirus began to emerge from Wuhan, China, the U.S. Health and Human Services called a press conference in Washington, D.C. SARS-CoV-2 had infected thousands, millions were quarantined in China, and no decent treatment for the virus existed. “We’re looking at the worst scenario that this becomes a bigger outbreak,” Anthony Fauci, director of the National Institute of Allergy and Infectious Disease (NIAID), told reporters. To stop that outbreak and save lives, he said, the world needs a vaccine.
With the extent of the outbreak still unclear, at least five research teams are working furiously to develop a vaccine, using a variety of strategies to spur an effective immune response. But vaccine development can be slow, relative to the speed of transmission of SARS-CoV-2. In the cases of Zika, Ebola and the 2009 swine flu, vaccine development took at least six months, which is still celebrated as record speed.
Preclinical and clinical trials consume a lot of that time, as does scaling up manufacturing and distribution. But developing a prototype vaccine can take significant time as well. In years past, vaccines have often come too late to help stem the initial outbreak. This time researchers are stepping up the pace — and life science companies are emerging as key players in the development of a SARS-CoV-2 vaccine.
The race to develop a vaccine began in earnest on January 10, when the Chinese Centers for Disease Control released the complete genome sequence for then-unnamed coronavirus to public databases. One life science company, Genscript, based in Piscataway, New Jersey, took particular notice.
The company, whose manufacturing facilities are located in China and the U.S., has made it a mission to support the development of a SARS-CoV-2 vaccine; many of its Chinese scientists canceled their holidays to keep the lab running around the clock. Less than two weeks after the viral genome sequence was released, Genscript released a new SARS-CoV-2 detection assay for initial screening, and its researchers were fielding requests for genes, proteins and peptides from vaccine developers across the world.
To speed development of prototype vaccines, Genscript delivers full-length genes in a matter of days. To do so, the company first synthesizes thousands of snippets of DNA on an array of computer-controlled platinum electrodes over a semiconductor chip, by adding one nucleotide at a time to each growing snippet. After they synthesize the snippets, or oligonucleotides, they use a proprietary technology to stitch them together to produce long strands of high-quality DNA, which they then clone and sequence to verify that there are no mistakes.
Novavax, a late-stage biopharmaceutical company based in Gaithersburg, Maryland, turned to Genscript to speed development of a recombinant nanoparticle vaccine. “We never touch the virus,” says Gregory Glenn, the company’s president of research and development. “We design the gene we want, and they make it,” he says.
Soon after the full SARS-CoV-2 genome sequence went live on 10 January, Novavax ordered from Genscript the full-length gene for SARS-CoV-2’s spike protein. This syringe-like protein latches on to cells in the respiratory-tract and injects them with viral RNA.
Novavax, which focuses on developing next-generation vaccines for serious infectious diseases, plans to insert the full-length spike gene into a baculovirus, a virus that infects insect cells. When that virus infects lab-grown insect cells, it produces coronavirus spike protein that’s folded and sugar-coated as if human cells had produced it, Glenn says.
Novavax will then insert the spike protein into a micelle, an artificial membrane system the size of a virus particle. The micelle displays parts of the spike protein called epitopes that evolve very little, and are therefore similar from one strain of coronavirus to the next. These epitopes are normally inaccessible to the immune system, but in Novavax’s vaccine, they’re “naked to the world,” Glenn says. For that reason, they provoke an immune response that should target many variants of the spike protein, and therefore ward off all the variants of SARS-CoV-2 people may yet encounter.
Even today, constructing a full-length gene like the spike gene takes quality engineering that’s difficult to pull off, and for Novavax, every day mattered. Genscript synthesized the SARS-CoV-2 spike gene and delivered it in just three days. “That was remarkable,” Glenn says.
Since then Novavax has been moving apace with their vaccine, and will be in clinical trials by early summer, Glenn says. And other vaccine developers are pushing forward at breakneck speed, using DNA vaccines, messenger RNA vaccines or a vaccine called a molecular clamp that stabilizes viral proteins. Which one will ultimately prevail is anyone’s guess.
Nonetheless, the race to the clinic is on, and lives hang in the balance.
To learn more about the plasmids built specifically to study SARS-CoV-2 and speed new detection and therapeutic research, visit this page on GenScript's open-source plasmid repository platform, MolecularCloud.