Coronavirus: The race to find a vaccine against the world’s enemy

A race is being fought from every corner of the world to find a coronavirus vaccine. It is an immense effort involving co-operation between countries, institutions and researchers in a collective move against one enemy; the greatest health threat to humanity in a century.

Some 35 companies and academic institutions – some with Irish virologists and immunologists – are involved. At least four say they already have candidates being tested in animals and want to test on humans. But this requires careful evaluation of need; risk in cutting some corners (understandable given what’s unfolding) and efficacy.

The one discordant note was a report – later denied – that US president Donald Trump was seeking to acquire the expertise of a German biotech company regarded by many as leading the race. CureVac hopes to have an experimental vaccine ready by June or July, and will then seek go-ahead from regulators for human testing with a view to it being available by year end.

Unprecedented speed is thanks in large part to China. It sequenced the genetic make-up of Sars-CoV-2 (its medical term) and shared it in January, allowing researchers around the world to grow the live virus and study how it invades human cells and makes people sick.

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This also assisted in developing testing kits to confirm infectivity and potential antiviral agents. Past experience with Sars, Mers, H1N1 and swine flu also suggests vaccine development could be quicker than before.

Another vaccine developed by US biotech company Moderna is to be injected into healthy volunteers in Seattle shortly. "This was reputedly prepared and ready for testing in 42 days, which is an incredibly rapid response," says Trinity College Dublin immunologist Prof Kingston Mills.

A vaccine is the single best way to achieve “herd immunity”, ie protection for whole populations, while vaccination of care givers and medical staff would do a lot to prevent exposure to the more vulnerable.

Dr Cillian de Gascun, director of the National Virus Reference Laboratory in University College Dublin says the technology required is not hugely challenging. There is a vaccine already in use in agriculture to prevent avian bronchitis virus – a coronavirus. The difficulty centres around demonstrating safety, efficacy and scaling up manufacturing.

He cites the case of generating a flu vaccine every year, work on which is conducted in February-March for use the following winter season. There is a six-month lead in but that is made possible by the body of built-up research. That kind of work has not been done with Covid-19. That is why the predominant view is that a vaccine is 12 to 18 months away.

Trials

A major difficulty will be where trials are conducted. They are usually done where there is uncontrolled community transmission, de Gascun explains, yet most places in the world are now locked down or subject to social isolation. Moreover, large numbers are required, because we are talking about vaccinating whole populations.

That means tens of thousands of people at the critical Phase 3 stage of evaluation. It may be a case of going back to China as it has lifted restrictions (except on foreign travel).

Developing a vaccine is not straightforward; there are many unknowns. It remains to be seen if it’s going to become a seasonal flu-like virus. While Sars became extinct because of effective infection controls, de Gascun notes Covid-19 has challenging characteristics. These include a very high “viral load” initially, which may even be high before the onset of symptoms, and yet there is no link between viral load on how sick a person becomes.

A big question is what happens when containment is lifted. He believes a certain proportion of people will have immunity. If it behaves like flu, there is a risk it might come back in the autumn. “It’s going to be here for a while. The big question is: does it become like seasonal flu? It’s too early to say.”

The first phase in testing sees a small number of healthy adults given the vaccine. The Seattle trial will enrol 45 adults. Phase 2 trials test safety in a larger group of people and look for expected effects in the body. The stringent testing is Phase 3 when many thousands of people are required.

The European Medicines Agency and US Food and Drug Administration determine if the vaccine can be licensed. This might be based on more limited safety and efficacy testing than normal, if regulators speed up decision making. "They may change the rules when there's a pandemic.[BUT] they will not regulate a vaccine unless happy it is safe and effective," Mills underlines.

He acknowledges frustration among the public about the absence of a drug or vaccine. “But if you put something on the market that doesn’t work or causes side effects, then you lose the confidence of the public.”

Many are involved because small groups of people may turn out to be at risk of rare side effects because of age, genetic makeup or underlying health conditions. On the upside, Sars-CoV-2 is not expected to change much whereas influenza tends to mutate.

Age-targeted formulations

Irish scientist Dr David Dowling is looking at how substances called adjuvants could render Covid-19 vaccines more effective. The aim is to design formulations that work well in older people – the most vulnerable – which can be delivered widely and affordably, where a lesser dose is needed but protection is conferred.

“Right now, we are working with collaborators in moving forward several vaccines against the virus,” says Dowling, principal investigator with the Precision Vaccines Program at Boston Children’s Hospital in the US.

“Our research has already shown we can do this age targeting for babies with the pneumococcal vaccine – a vaccine that’s very expensive to produce,” he explains. “Delivering the pneumococcal vaccine along with adjuvants that stimulate the immune response in babies means you need less of the actual vaccine for it to work, so it’s more cost-effective.”

With colleagues at Harvard Medical School they are researching new, age-targeted formulations using an existing experimental vaccine against the 2003 Sars coronavirus, to prove the concept. They will need time to be developed and tested, but he hopes this will lead to more useful vaccines.

“I would like to see several vaccines available against this coronavirus, because different groups of people may need different vaccine approaches,” says Dowling, who is from Bray and got his PhD from Dublin City University. “If we don’t take factors like age-related changes in immune responses and vaccine cost into account, this could potentially lead to shortages and conflicts later on. It is worth investing in the research on this now.”

The Coalition for Epidemic Preparedness Innovations is supporting many of the lead vaccine contenders. Created in 2017 to speed vaccine development for new diseases because of heightened risk of a pandemic from a flu or novel coronavirus, it's funded by governments in Germany, Japan and Norway, the Bill & Melinda Gates Foundation and Wellcome Trust.

Because a vaccine is up to 18 months away, other treatments assume greater importance, notably antivirals, de Gascun says. A number of options are already in clinical trials. They are easier to do with a different risk-benefit ratio. All told, it’s an easier sell in terms of investment, doing the checks and going into production. But scaled-up action on both fronts must be the global priority.