In early January 2020, Chinese scientists released genetic information on the coronavirus causing an outbreak of SARS-like illness in Wuhan, China. The Vaccine Research Institute at the US National Institutes of Health (NIH) immediately began development of a new vaccine.
After the 2003 SARS outbreak, it took 20 months from the release of the viral genome to get a vaccine ready for human trials. The zika virus took six months. Now, the NIH is pushing to have a vaccine ready for testing in three to six months. The race is on.
Image: Passengers at Shanghai airport wearing protective face masks during coronavirus outbreak in January 2020.
The NIH team took the template for a SARS vaccine and swapped enough code from the new virus to start a new vaccine. Researchers, having experience with SARS, already knew which part of the virus to choose for the vaccine’s antigen, a sort of red flag for the immune system. This synthetic antigen will prod the body to make antibodies.
‘Vaccines for this novel coronavirus will target the spike protein,’ explains microbiologist Vineet Menachery at the University of Texas Medical Branch, US. Spike glycoproteins stud the surface of the virus and bind to a receptor (ACE2) on human lung cells, analogous to a key for breaking in. Developing antibodies that will bind to the spike protein is one way to stop the virus invading human cells.
Biotech company Moderna in Cambridge, Massachusetts, plans to use the virus genetic information to create synthetic messenger RNA (mRNA) that carries the recipe to make proteins inside human cells, turning them into factories for churning out vaccine antigens. Moderna has mRNA vaccines for respiratory syncytial virus (RSV), Zika and avian influenza H7N9 in clinical trials, and recently initiated a Phase 2 trial for its cytomegalovirus vaccine. The company’s manufacture of the mRNA vaccine against 2019-nCoV will be funded by the Coalition of Epidemic Preparedness Innovations (CEPI).
Inovio and Johnson & Johnson are two other companies with vaccine strategies against the Wuhan coronavirus. Inovio, in Pennsylvania, received a $9m grant from CEPI and announced plans to test its DNA vaccine in China. In 2019, Inovio announced positive results from its first-in-man trial of a DNA vaccine against the MERS coronavirus. This is a DNA plasmid vaccine that expresses the spike glycoprotein from MERS virus. The plasmid transits into a recipient’s cells after they are hit by a short electric buzz via a specialised medical device. The vaccine for the Wuhan virus will take a similar approach.
‘The advantage of the mRNA and the DNA approach is that you can move quickly into design and manufacture,’ says Peter Hotez, a virologist at Baylor College of Medicine in Houston, Texas. ‘The disadvantage is that there has never been a licensed DNA or RNA vaccine.’ Historically, these candidates have not transitioned well from mice studies to humans. Although the companies say they can overcome these hurdles, Hotez says authorities should not overlook older, established technology.
His own group developed a SARS vaccine based on a small portion of the spike protein that binds to the host cell receptor. ‘It does take time to scale up production, and it may need a cold chain,’ he notes. He would like to test the efficacy of his SARS vaccine in patients with the Wuhan virus, and in parallel develop a similar recombinant vaccine against the novel virus itself. ‘We are ready to go, but don’t have the resources. Either someone in China or the NIH could help us accelerate this.’
Johnson & Johnson announced that it will use its adenovirus technology, a similar strategy to that used in its Ebola vaccine, currently deployed in Congo and Rwanda. The company said it could take eight to 12 months before this vaccine reaches clinical trials.
CEPI is also supporting researchers at the University of Queensland, Australia, who will deploy a ‘molecular clamp’ strategy. This involves making viral surface proteins, which attach to cells during infection, clamping them into shape - making it easier for the immune system to recognise the correct antigen. The approach has protected lab animals from flu and Ebola.
‘It will be relatively easy to target the spike protein of a novel coronavirus,’ notes Menachery. ‘The barrier will be safety testing in humans.’ This will be the slowest step too, he adds. ‘I imagine you could see its use in people by the early summer,’ adds Menachery. ‘However, wide distribution usually requires more testing. Normally I’d predict more than a year, but with the current outbreak, we may see more rapid response and implementation.’
A vaccine may only become available after the Wuhan virus has finished blazing around the world. ‘You need three to six months to make and trial a vaccine,’ says Meriadeg Le Gouil, a virologist at the University of Caen in Normandy, France, ‘This virus is going to change a lot in that time.’ Whether the vaccine will still be useful is uncertain, he adds. ‘I’m not saying we shouldn’t develop a vaccine. It is a necessity. But the impact of a vaccine in future is highly unpredictable.’
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