About 35 companies and academic institutions are rushing to create such a vaccine, at least four of which already have candidates they have tested on animals. The first of these – produced by the Boston-based biotechnology company Moderna – will soon enter human trials.
This unprecedented speed is largely due to early Chinese efforts to sequence the genetic material of Sars-CoV-2, the virus that causes Covid-19. China shared the footage in early January, allowing research groups around the world to develop the living virus and study how it invades human cells and makes people sick.
But there is another reason in advance. Although no one could have predicted that the next infectious disease that would threaten the world would be caused by a coronavirus – influenza is generally considered to pose the greatest risk of pandemic – the vaccinologists had covered their bets by working on “prototypes” pathogens. “The speed at which we have [produced these candidates] relies heavily on investment to understand how to develop vaccines for other coronaviruses, ”said Richard Hatchett, CEO of the Oslo-based Coalition for Epidemic Preparedness Innovations (Cepi), which is leading efforts to fund and coordinate the Covid-19 vaccine. development.
Coronaviruses have caused two other recent epidemics – severe acute respiratory syndrome (Sars) in China in 2002-2004 and Middle East respiratory syndrome (Mers), which started in Saudi Arabia in 2012. In both cases, Work began on vaccines which were later put aside when the outbreaks were brought under control. A company, Novavax, based in Maryland, has now re-used these vaccines for Sars-CoV-2, and says it has several candidates ready to enter human trials this spring. Moderna, for its part, built on previous work on the Mers virus at the United States 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 band of ribonucleic acid (RNA) inside a spherical protein capsule which is covered with spikes. The spikes attach to receptors on the surface of cells lining the human lung – the same type of receptor in both cases – allowing the virus to enter the cell. Once inside, he hijacks the reproductive machinery of the cell to produce more copies of himself, before leaving the cell again and killing it in the process.
All vaccines work on the same basic principle. They present some or all of the pathogen to the human immune system, usually in the form of an injection and in a low dose, to induce the system to produce antibodies against the pathogen. Antibodies are a kind of immune memory that, once triggered, can be quickly mobilized again if the person is exposed to the virus in its natural form.
Traditionally, immunization has been carried out using live and weakened forms of the virus, or some or all of the virus once it has been inactivated by heat or chemicals. These methods have drawbacks. The living form can continue to evolve in the host, for example, potentially recovering part of its virulence and making the recipient sick, while higher or repeated doses of the inactivated virus are necessary to achieve the necessary degree of protection. . Some of the Covid-19 vaccine projects use these proven approaches, but others use newer technologies. A more recent strategy – the one Novavax uses, for example – is building a “recombinant” vaccine. This involves extracting the genetic code from the protein tip on the surface of Sars-CoV-2, which is the part of the virus most likely to cause an immune response in humans, and sticking it into the genome d ‘bacteria or yeast – forcing these microorganisms to produce large amounts of protein. Other, even more recent, approaches bypass the protein and build vaccines based on the genetic instruction itself. Moderna and another Boston company, CureVac, both manufacture Covid-19 vaccines from messenger RNA.
Cepi’s initial portfolio of four funded Covid-19 vaccine projects was heavily geared toward these more innovative technologies, and last week it announced partnership funding of $ 4.4 million (£ 3.4 million) ) with Novavax and a vectorized vaccine project from the University of Oxford. “Our experience with vaccine development is that you can’t predict where you’re going to stumble,” says Hatchett, which means diversity is key. And the step where any approach is most likely to fall is that of clinical or human trials which, for some candidates, are about to start.
Clinical trials, the essential precursor to regulatory approval, generally take place in three phases. The first, involving a few dozen healthy volunteers, tests the safety of the vaccine, monitoring for side effects. The second, involving several hundred people, usually in a part of the world affected by the disease, examines the effectiveness of the vaccine, and the third does the same for several thousand people. But there is a high level of attrition as the experimental vaccines go through these phases. “Not every horse that leaves the starting grid will finish the race,” said Bruce Gellin, who heads the Washington DC-based global vaccination program for the Washington DC Sabin Vaccine Institute.
There are good reasons for this. Either the candidates are not safe, or they are ineffective, or both. Failure screening is essential, which is why clinical trials cannot be skipped or rushed. Approval can be expedited if regulatory authorities have already approved similar products. The annual flu shot, for example, is the product of a well-established assembly line in which only one or a few modules need to be updated each year. In contrast, Sars-CoV-2 is a new human pathogen, and many of the technologies used to make vaccines are relatively untested as well. No vaccine made from genetic material – RNA or DNA – has been approved to date, for example. Covid-19 candidate vaccines should therefore be treated as new vaccines, and as Gellin says: “While there is pressure to get things done as quickly as possible, it is really important not to take shortcuts. ”
An illustration of this is a vaccine that was produced in the 1960s against the respiratory syncytial virus, a common virus that causes cold symptoms in children. In clinical trials, this vaccine has been shown to worsen these symptoms in infants who then get the virus. A similar effect was observed in animals that received an early Sars experimental vaccine. It was later modified to eliminate this problem, but now that it has been reused for Sars-CoV-2, it will have to undergo particularly rigorous safety tests to exclude the risk of worsening the disease.
It is for these reasons that taking a candidate vaccine until regulatory approval generally takes a decade or more, and why President Trump caused confusion when at a White House meeting on 2 March, he lobbied for a vaccine to be ready by the November US elections – an impossible deadline. “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. It’s already extremely fast, and that assumes there won’t be any problems.
In the meantime, there is another potential problem. As soon as a vaccine is approved, it will be needed in large quantities – and many organizations in the race for the Covid-19 vaccine simply do not have the production capacity to do so. The development of vaccines is already a risky business, in commercial terms, because so few candidates approach the clinic. Production facilities tend to be adapted to specific vaccines, and scaling them up when you don’t yet know if your product will be successful is not commercially feasible. Cepi and similar organizations exist to assume part of the risk, which encourages companies to develop essential vaccines. Cepi plans to invest in the development of a Covid-19 vaccine and increase parallel manufacturing capacity, and earlier this month it appealed for $ 2 billion to allow it to do so.
Once the Covid-19 vaccine is approved, a new set of challenges will arise. “Obtaining a vaccine that has been shown to be safe and effective in humans is at best about a third of the way required for a global immunization program,” said global health expert Jonathan Quick of Duke University in North Carolina, author of The end of epidemics (2018). “Viral biology and vaccine technology may be the limiting factors, but politics and economics are much more likely to be the barrier to vaccination.”
The problem is to make sure that the vaccine gets to everyone who needs it. It is a challenge even within countries, and some have developed guidelines. In the scenario of an influenza pandemic, for example, the United Kingdom would prioritize the vaccination of health and social service workers, as well as those considered to be most at medical risk – including children and pregnant women – with the overall goal of keeping sickness and death rates as low as possible. possible. But in the event of a pandemic, countries also have to compete for drugs.
Because pandemics tend to hit countries with the most fragile and least funded health systems hardest, there is an inherent imbalance between vaccine needs and purchasing power. During the 2009 H1N1 flu pandemic, for example, vaccine supplies were cut by countries that could afford it, leaving the poorest to run out. But you can also imagine a scenario where, for example, India – a major supplier of vaccines to the developing world – decides not without reason to use its vaccine production to protect its own population of 1.3 billion inhabitants before exporting.
Outside pandemics, WHO is bringing governments, charitable foundations and vaccine manufacturers together to agree on a strategy for equitable global distribution, and organizations like Gavi, the vaccine alliance, have developed mechanisms for innovative financing to raise funds on the markets to ensure the supply of the poorest countries. But every pandemic is different, and no country is bound by an arrangement proposed by the WHO – leaving many unknown. As Seth Berkley, CEO of Gavi, points out, “The question is, what will happen in a situation where you have national emergencies? ”
It is debated, but it will take some time to see how it will unfold. The pandemic, says Wilder-Smith, “will likely have peaked and waned before a vaccine is available.” A vaccine could still save many lives, especially if the virus becomes endemic or in perpetual circulation – like the flu – and there are other epidemics, possibly seasonal. But until then, our best hope is to contain the disease as much as possible. To repeat the sage advice: wash your hands.
• This article was modified on March 19, 2020. An earlier version incorrectly stated that the Sabin Vaccine Institute was collaborating with the Coalition for Epidemic Preparedness Innovations (Cepi) on a Covid-19 vaccine.