Dr. Melanie Saville, the Director of Vaccine Development at the Coalition for Epidemic Preparedness Innovations (CEPI), discusses what a successful vaccine against COVID-19 would involve, some of the unknowns and challenges that vaccine developers are wrestling with, and how CEPI will ensure equitable distribution of a vaccine.

How can CEPI measure success across its COVID-19 vaccine portfolio?

We manage our portfolio to make sure the most promising vaccines move forward, based on three key criteria of speed, scale, and access. The portfolio currently consists of nine vaccines, and we are currently assessing other potential candidates to invest in. We hope to progress at least three candidates from our portfolio to licensure.

When assessing potential candidates against our key criteria, the starting point is what’s called the ‘target product profile’ for a vaccine: essentially what you’d like to see in terms of the effectiveness and safety profile of a vaccine. These are the minimum requirements. The U.S. Food and Drug Administration (FDA) has set the bar at 50% more effective than placebo at preventing the disease, and obviously, you’d want higher than that.

The Holy Grail is prevention of infection — prevention of transmission from one person to another. But I think we need to manage people’s expectations. A good way of looking at it is to consider seasonal influenza. That’s a disease that’s not dissimilar to COVID-19. And we manage it well globally through vaccination, which is extremely successful at preventing morbidity and mortality in the elderly and high-risk populations even though in the elderly, vaccines are [sometimes] not 100% protective.

What other criteria does CEPI use to consider the pros and cons of different vaccine candidates?

It’s very complex to weigh up what each individual candidate or platform can offer, in addition to preventing disease and potentially preventing transmission.

You might find that one vaccine works really well in 20-year-olds but doesn’t work so well in the elderly. So, we have to look at who we are trying to prevent disease in, and to make sure we have a portfolio of vaccines that can protect at-risk populations, which are diverse. You would ideally want a vaccine that can be used in pregnant women, and a vaccine that you might want to use in children, if needed — and that might be different from another vaccine. We should avoid giving the impression that one vaccine will provide the answer to everything.

And then there are other criteria we look at when we’re evaluating CEPI’s portfolio, such as manufacturing, and scalability. There’s also delivery — and the key point here of one-dose versus two-doses. The ideal would be a one-dose vaccine for a few reasons. One reason is faster protection: a single dose could be used potentially to control an outbreak as well as vaccinate people for general protection, whether they’re at significant risk or not. There’s also far more compliance with a single-dose regimen. And for vaccination campaigns, a single dose is far easier and far less expensive. In low-income and middle-income countries, a single-dose campaign is likely to be more successful than a two-dose regimen. We’ve identified that’s a gap in our portfolio and we want to prioritise a single-dose regimen as one of our priorities.

And then, there’s the cold chain, which is important from an access perspective. Whether your vaccine needs to be stored at minus 70°C or 4°C are very different things. You’re adding a huge amount of complexity if you need to build a minus 70°C requirement into a cold chain. Obviously, we want to move those vaccine candidates forward with the best overall profile. I’d rather give a vaccine that’s at minus 70°C and 90% protective than one that can be stored at 2°C to 8°C but which is only 10% protective, as an example. You just have to weigh everything up together to get the best balance.

Source: Wellcome

There’s a debate around the length of immunity. Does that complicate vaccine development?

This is a really important question. We are 9 months into the disease. So that’s the maximum data that we have at the moment. With respiratory diseases in particular, we do see waning antibodies. And we don’t know whether that waning of antibody will equate to loss of protection. We need to gather data to see whether people are being re-infected or not, and what the disease looks like, if they are re-infected. All of that information will help vaccine developers decide if booster doses of vaccine might be needed in the future, for example. So, it’s important that the work is being done. We need to follow it up in the longer term. We need to see how that waning of antibody from natural infection compares with waning antibody in vaccinated individuals, and continue to build on how best to use vaccines.

How does CEPI’s portfolio approach support the different vaccine programs?

One of the things we’re investing in is centralised laboratory testing, so scientists can use the same assays [tests for detecting presence of viral material, including antibodies]. We want to develop a gold-standard assay, so vaccine developers and regulators can understand and compare the merits of each of the vaccines that are being developed. We’re looking at making sure that people are using either the same or at least similar endpoints in clinical trials, so the definitions are the same. We’re putting a lot of effort into these types of activities, so we don’t end up comparing apples and pears.

Can we think in terms of ending the pandemic?

What does ending the pandemic mean? We need to recognise that we’re likely to get to a situation like seasonal flu. Or take measles as another example: we have a highly effective vaccine against measles, but measles still exists. We need to manage expectations. When we say: end the pandemic, we don’t mean we are ending the disease, but we can end the acute situation, which is paralysing the globe.

How is CEPI working to ensure equitable access to COVID-19 vaccines?

CEPI, Gavi, the Vaccine Alliance, and the World Health Organization have launched a global initiative called COVAX, which aims to deliver fair and equitable access to COVID-19 vaccines. Making vaccines available to those who need them most — regardless of where they live or whether they can afford to pay — is the fastest, as well as the fairest, way to bring the pandemic to a manageable stage. We know for sure that initial global demand for COVID-19 vaccines is going to vastly outstrip supply, so we will have to carefully manage this scarce resource so that it has the greatest possible impact.

Together our goal is to produce two billion doses of vaccine and distribute them globally and fairly by the end of 2021. All countries which participate in COVAX, regardless of income levels, will have equal access to these vaccines once they are developed, which should be enough to protect high risk and vulnerable people, as well as frontline healthcare workers. By protecting those most at risk first — wherever they are on the planet — we’ll end the acute phase of the pandemic more rapidly.

This piece originally appeared on CEPI’s website and has been edited and republished with permission.

Featured Photo: CEPI