Even at their most effective – and draconian – containment strategies have only slowed the spread of the respiratory disease Covid-19. With the World Health Organization finally declaring a pandemic, all eyes have turned to the prospect of a vaccine, because only a vaccine can prevent people from getting sick.
About 35 companies and academic institutions are racing to create such a vaccine, at least four of which already have candidates they have been testing in animals. The first of these – produced by Boston-based biotech firm Moderna – will enter human trials imminently.
This unprecedented speed is thanks in large part to early Chinese efforts to sequence the genetic material of Sars-CoV-2, the virus that causes Covid-19. China shared that sequence in early January, allowing research groups around the world to grow the live virus and study how it invades human cells and makes people sick.But there is another reason for the head start. Though nobody could have predicted that the next infectious disease to threaten the globe would be caused by a coronavirus – flu is generally considered to pose the greatest pandemic risk – vaccinologists had hedged their bets by working on “prototype” pathogens. “The speed with which we have [produced these candidates] builds very much on the investment in understanding how to develop vaccines for other coronaviruses,” says Richard Hatchett, CEO of the Oslo-based nonprofit the Coalition for Epidemic Preparedness Innovations (Cepi), which is leading efforts to finance and coordinate Covid-19 vaccine development.Coronaviruses have caused two other recent epidemics – severe acute respiratory syndrome (Sars) in China in 2002-04, and Middle East respiratory syndrome (Mers), which started in Saudi Arabia in 2012. In both cases, work began on vaccines that were later shelved when the outbreaks were contained. One company, Maryland-based Novavax, has now repurposed those vaccines for Sars-CoV-2, and says it has several candidates ready to enter human trials this spring. Moderna, meanwhile, built on earlier work on the Mers virus conducted at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.
Sars-CoV-2 shares between 80% and 90% of its genetic material with the virus that caused Sars – hence its name. Both consist of a strip of ribonucleic acid (RNA) inside a spherical protein capsule that is covered in spikes. The spikes lock on to receptors on the surface of cells lining the human lung – the same type of receptor in both cases – allowing the virus to break into the cell. Once inside, it hijacks the cell’s reproductive machinery to produce more copies of itself, before breaking out of the cell again and killing it in the process.
All vaccines work according to the same basic principle. They present part or all of the pathogen to the human immune system, usually in the form of an injection and at a low dose, to prompt the system to produce antibodies to the pathogen. Antibodies are a kind of immune memory which, having been elicited once, can be quickly mobilised again if the person is exposed to the virus in its natural form.
Traditionally, immunisation has been achieved using live, weakened forms of the virus, or part or whole of the virus once it has been inactivated by heat or chemicals. These methods have drawbacks. The live form can continue to evolve in the host, for example, potentially recapturing some of its virulence and making the recipient sick, while higher or repeat doses of the inactivated virus are required to achieve the necessary degree of protection. Some of the Covid-19 vaccine projects are using these tried-and-tested approaches, but others are using newer technology. One more recent strategy – the one that Novavax is using, for example – constructs a “recombinant” vaccine. This involves extracting the genetic code for the protein spike on the surface of Sars-CoV-2, which is the part of the virus most likely to provoke an immune reaction in humans, and pasting it into the genome of a bacterium or yeast – forcing these microorganisms to churn out large quantities of the protein. Other approaches, even newer, bypass the protein and build vaccines from the genetic instruction itself. This is the case for Moderna and another company, CureVac, both of which are building Covid-19 vaccines out of messenger RNA.