Speed, success, diplomacy and delivery: the formula for a Covid-19 vaccine

Numerous coronavirus vaccines are being developed, but none is assured of success

It may feel like the Covid-19 pandemic has been with us for an age, but it only emerged early this year. And from the perspective of developing a new vaccine, a few months is the blink of an eye. Vaccines typically take several years to move through research, development, testing and large-scale manufacture before making it into widespread use.

But with Covid-19 things are different.

The push is on to develop a vaccine at unprecedented speed against the SARS-CoV-2 virus that causes Covid-19. And while the World Health Organisation recently warned that there may never be a "silver bullet", effective vaccines could play an important role in protecting human health from this disease.

So how might such vaccines work? Do we need several types? And what barriers do they need to overcome?

Different approaches

As of early August, more than 180 potential SARS-CoV-2 vaccines are in various stages of research and testing worldwide, with a handful now in larger-scale human trials. There are several approaches to developing a Covid-19 vaccine, says Prof Kingston Mills, who is professor of experimental immunology at Trinity College Dublin.

One is the tried-and-tested method of taking the whole SARS-CoV-2 virus, inactivating it so it can’t cause disease and then introducing it to the body. Then the immune system can take note of it and remember what it looks like should the real SARS-CoV-2 virus ever try to infect.

“This is an old-fashioned way of doing it, it is how the injectable polio virus vaccine worked,” says Mills. “Progress is being made with this approach for SARS-CoV-2, but the issue here is that it is difficult to make large-scale amounts of this type of vaccine quickly.”

A slightly more targeted method takes a part of the SARS-CoV-2 virus (often the spike protein sticking out of its surface), and introduces that into the body with an adjuvant, a material that helps to generate an immune response against the virus. Mills and colleagues at Trinity College Dublin are using this strategy in their research. “We are looking at how to deliver the spike protein in a way that encourages the body to develop a long-term memory of SARS-CoV-2,” he says.

A newer take on the SARS-CoV-2 vaccine uses genetic material from the virus to stimulate the body's immune system. The first SARS-CoV-2 vaccine to make it into human trials, developed by a company called Moderna in the United States, uses this approach. "This is a new technology for vaccination," says Mills. "It's smart, and it has been tested for some other viruses, but it has not been used in a licensed vaccine to date."

Another way is to take genetic instructions from the SARS-CoV-2 and put that into a vector virus. This carries the instructions into the body so that we make SARS-CoV-2 proteins, and that in turn generates an immune response. A group at Oxford University has recently shown that their vector virus carrying SARS-CoV-2 genetic material stimulates the human immune system to develop antibodies and other immune cells that kill cells infected with the Covid-19 virus.

Scaling up options

An advantage of using the genetic material from SARS-CoV-2 as a vaccine - whether by itself or carried in a vector virus - is that such a vaccine could be scaled up relatively rapidly, notes Mills. “These are relatively new technologies in vaccination terms, and they have the potential to be made quickly.”

As well as quantity, in an ideal world we would have several types of vaccine against Covid-19 in use, according to Mills, but we have to be realistic. “It depends on how things work out, but I think it will be next year before we have any vaccine in wide use,” he says. “Of course it would be great to have even one, and in that case we would need to ensure that high-risk groups such as healthcare workers could get it, but ideally we want to have more than one type of vaccine, that would be our best bet.”

Need for speed

The steps to develop a Covid-19 vaccine are similar to those we have seen with previous emerging infectious diseases such as Zika and Ebola, explains Dr Anne Moore, a senior lecturer at University College Cork's School of Biochemistry and Cell Biology.

But what sets Covid-19 apart is the way investment is happening simultaneously in development (finding the vaccine), manufacturing (making the vaccine) and distribution, notes Moore. “The usual process of getting a vaccine into use takes longer largely because of securing investment of resources to be able to move to the next step. Usually, we first gain confidence that a vaccine has a good potential for protecting against infection before committing to large-scale manufacture,” she says.

“However, for Covid-19 vaccines, multiple manufacturing facilities are being prepared or repurposed to produce millions of doses of a vaccine that could fail in the clinic, or that may not be used in the millions. Governments, funding bodies and companies are taking the risk in this investment in the interests of expediency, knowing that not all vaccines will likely make it to final licensing and use. Mass manufacturing in parallel to trials means that doses will be ready to deploy if the trial works.”

This parallel investment, as well as multiple vaccines entering the final phases of clinical testing at the same time, help to explain the ambition of getting a Covid-19 vaccine into widespread use as soon as possible, explains Moore.

“It’s nothing to do with trial setup or rigorous analysis of the safety or immunity or how well the vaccine protects - you cannot shorten this timeframe,” she says. “All of these essential analyses must and will occur to the highest standards, as we have seen with the vaccine trials that have occurred so far. Large clinical trials in tens of thousands of people will give a really good insight into safety and efficacy in diverse populations.”

Need for diplomacy

Ultimately, international diplomacy will be key to any proven vaccine doing its job, notes Moore. “There needs to be a global understanding that the vaccine first needs to be deployed to where it is most needed, to the populations that are at the highest risk of suffering from Covid-19 disease,” she says. “We have to look at how this can be defined, for example is it healthcare workers globally, or is it entire populations where the infection rate is increasing, or both?”

There are also the practicalities of delivering it. “This will take time,” says Moore, whose own research at UCC is on a patch that can deliver vaccines at room temperature and without the need for hypodermic needles. “In the longer term, maybe there will be a vaccine that can be self-administered, but more immediately we will need clinics to deploy a Covid-19 vaccine, and that people are willing to take it.”

Moore hopes that everything will line up to protect us. "We might know that a vaccine works by the end of 2020, but it could be late 2021 before we see it in Ireland, " she says. "And if vaccination works, eventually at a global level we could plan for eradication of SARS-CoV-2. It's ambitious but possible - worldwide we eradicated smallpox through immunisation and we have almost eliminated polio virus.

“If you compare Ireland in the 1950s with the reality of polio compared to the 1960s onwards, you can see how the world we live in can be positively impacted by vaccination to reduce or eliminate a circulating disease.”

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