Though nobody could have predicted that the next infectious disease to threaten the globe would be caused by a coronavirus –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 – started human trials.

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.

*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 Coalition for Epidemic Preparedness Innovations (Cepi).

coronaviruses have caused two other 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.

Another American research institute Novavax,

has now repurposed those vaccines for Sars-CoV-2, and says it has several candidates ready to enter human trials this spring.

 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 Boston company, CureVac, both of which are building Covid-19 vaccines out of messenger RNA.

“Our experience with vaccine development is that you can’t anticipate where you’re going to stumble,” says Hatchett, meaning that diversity is key. And the stage where any approach is most likely to stumble is clinical or human trials, which, for some of the candidates, are about to get under way.

Clinical trials, an essential precursor to regulatory approval, usually take place in three phases. The first, involving a few dozen healthy volunteers, tests the vaccine for safety, monitoring for adverse effects. The second, involving several hundred people, usually in a part of the world affected by the disease, looks at how effective the vaccine is, and the third does the same in several thousand people. But there’s a high level of attrition as experimental vaccines pass through these phases. “Not all horses that leave the starting gate will finish the race,” says Bruce Gellin, who runs the global immunisation programme.

There are good reasons for that. Either the candidates are unsafe, or they’re ineffective, or both. Screening out duds is essential, which is why clinical trials can’t be skipped or hurried. Approval can be accelerated if regulators have approved similar products before.  Sars-CoV-2 is a novel pathogen in humans, and many of the technologies being used to build vaccines

are relatively untested too. No vaccine made from genetic material – RNA or DNA – has been approved to date, for example. So the Covid-19 vaccine candidates have to be treated as brand new vaccines, and as Gellin says: “While there is a push to do things as fast as possible, it’s really important not to take shortcuts."

It’s for these reasons that taking a vaccine candidate all the way to regulatory approval typically takes a decade or more

“Like most vaccinologists, I don’t think this vaccine will be ready before 18 months,” says Annelies Wilder-Smith, professor of emerging infectious diseases at the London School of Hygiene and Tropical Medicine. That’s already extremely fast, and it assumes there will be no hitches.

In the meantime, there is another potential problem. As soon as a vaccine is approved, it’s going to be needed in vast quantities – and many of the organisations in the Covid-19 vaccine race simply don’t have the necessary production capacity. Vaccine development is already a risky affair, in business terms, because so few candidates get anywhere near the clinic. Production facilities tend to be tailored to specific vaccines, and scaling these up when you don’t yet know if your product will succeed is not commercially feasible. Cepi and similar organisations exist to shoulder some of the risk, keeping companies incentivised to develop much-needed vaccines. Cepi plans to invest in developing a Covid-19 vaccine and boosting manufacturing capacity in parallel.                                                               Source…The Guardian