In 1934, in their spare time, two American biologists, Pearl Kendrick and Grace Eldering, developed a vaccine for whooping cough, then the biggest killer of children in the United States. Within four years their vaccine was being used throughout Michigan and within six it was being used nationwide. Whooping cough rapidly retreated.
Since then there have been spectacular advances in biology, including the identification of the genetic material, the ability to read its code, an understanding of the structure of viruses and the proteins from which they are made, plus knowledge of how immunity works. So why are we facing a wait of at least a year, maybe much more, for a vaccine for coronavirus? It has been one of the shocks of recent weeks to realise how little progress vaccine development has made. It’s still a bit of an art.
“Vaccine development,” warned Wayne Koff, president of the Human Vaccines Project, last year, “is an expensive, slow and laborious process, costing billions of dollars, taking decades, with less than a 10 per cent rate of success…There is clearly an urgent need to determine ways to improve not just the effectiveness of the vaccines themselves but also the very processes by which they are developed.”
A vaccine is an “antigen” protein that alerts the body’s immune system to an invader and against which an effective “antibody” is then created by the immune system. First, you have to give a version of the disease to an animal so that the vaccine can be tested. Ferrets are used for Sars, for instance. Getting a good animal model took two months in the case of Zika.
Then, traditionally, you have to grow the virus itself, in chicken eggs in the case of influenza. Then you have to work out how to inactivate it without altering it too much, what chemical adjuvants to add to stabilise it and so on – which can often take years. Inadequate inactivation caused an early polio vaccine to give polio to thousands of people in 1955. Contamination of the vaccine with other viruses is another problem – the SV40 monkey virus contaminated a lot of polio vaccines in the 1960s – but this is now largely preventable.
There are now at least two other higher-tech options to bypass this gardening-cum-cookery, but neither has produced a working vaccine for human beings yet. The first involves programming bacteria to manufacture one of the proteins in the virus. Novavax in Maryland has achieved this with the coronavirus’s spike protein. The second involves injecting the genetic instructions for the spike protein into a host body so its own cells manufacture the protein. This is what Moderna in Massachusetts is trying with promising results in mice followed by experiments with humans. Fortunately, both firms were already working on a similar coronavirus called Mers that has been killing small numbers of people in the Middle East.
But even supposing you get a vaccine that prevents infection with the disease in a mouse, there are huge hurdles to overcome. You have to prove it is safe in people. Some experimental vaccines exacerbate the disease: an early vaccine against Sars did this in mice and one against respiratory syncytial disease did the same in people.
Then you have to prove that the vaccine works. That is, it makes people immune to the disease for a long period and that this immunity applies against the latest mutations of the virus. That means recruiting lots of healthy people for lengthy trials over many months. Many promising candidates fail this test. The whole process costs billions of dollars and it is no coincidence that most vaccine development and testing takes place in India where volunteers for trials can be recruited.
By the time all this has happened, the epidemic is often over, which is why big pharmaceutical companies do not get much involved in vaccine development. In the case of Ebola, an experimental vaccine was first developed in November 2014. By the following June the epidemic was over and the firm was struggling to find volunteers for the latest trials.
It was precisely to solve this problem that the Coalition for Epidemic Preparedness Innovation (CEPI) was founded in 2017, funded by the Wellcome Trust, the Gates Foundation and the Indian and Norwegian governments, based in Oslo. But, although it is now funding lots of urgent projects on coronavirus, CEPI has yet to achieve the silver bullet of a vaccine-development process that is adaptable to any new disease and ready to go.
In an emergency it is of course possible to cut corners and strip away some of the red tape that surrounds clinical trials, but not all of it. Vaccines that make diseases worse, or cause severe reactions, are a real risk. In 1976 a handful of cases of swine flu led to mass immunisation of almost 25 per cent of Americans with a vaccine that caused a severe reaction among some people. It is likely that the vaccine killed more people than swine flu did.
Cures for coronavirus may yet emerge, but a vaccine is not coming to our rescue in the next few months.