In 1994 I spent six months working at a practice in the Yorkshire Moors as a trainee GP. Every Friday afternoon I helped the practice nurse with the weekly vaccination clinic for babies and children.
I did not particularly enjoy making countless little ones burst into tears as I injected them but I shall never forget what one of the GPs said to me about the clinic.
His words were, “This is the single, biggest contribution to the health of your patients you will ever make.”
He was right. We were not diagnosing any illnesses nor curing anyone from anything but we were preventing multiple diseases that had both maimed and killed thousands of children as little as 50 years previously.
Major scientific advances often result when the world faces a dire threat. World War 1 saw the rapid development of synthetic rubber, mass radio communications and the development of plastic surgery to treat those with horrific burns and disfigurement. (1)
World War 2 saw the advent of the jet engine, radar and penicillin. (2)
The world had not faced a major global health threat since the Spanish flu of 1918. Although diseases such as Ebola have brought devastation to some communities in Africa and malaria continues to be one of the biggest killers in many parts of the world, neither have threatened every nation at once or brought the whole world to a standstill.
COVID-19 has changed that. In 2020, for the first time in just over a century, the whole world faced the same disease at the same time. This propelled vaccine development back onto centre stage and, having succeeded in producing safe and effective vaccines against COVID-19, scientists are hoping that this is just the start of the development of vaccines against many other diseases.
Technological Advances
Professor Dame Sarah Gilbert of Oxford University led the team that created the AstraZeneca vaccine. She believes the time is right to work on vaccines for at least 12 more diseases.
Speaking to the BBC, Professor Gilbert used the analogy of baking a cake to explain what has changed in the approach to vaccine development.
She said: “The new generation of vaccines are quick to make and highly flexible. It's like decorating a cake. The old-school method of developing vaccines means you must go back to the raw materials and start from scratch for every vaccine you make. It is like starting with a bench of flour, sugar, eggs and butter. With this type of vaccine [Astra-Zeneca] most of the work has already been done - the cake has been pre-baked, it just needs to be "decorated" in order to match its target.” (3)
This way of developing vaccines is called "Plug-and-Play". The basic cake remains the same, you alter the decorations depending on which disease you want to make a vaccine for.
The “cake” the Oxford team are using is an inactivated chimpanzee virus that causes the common cold in chimps and is harmless to humans.
The two other COVID-19 vaccines currently being used in the UK, Pfizer and Moderna, use a similar “Plug-and-Play” approach.
However, there is a caveat to all of this. With any vaccine, scientists have to identify the specific part of the virus it will need to target. With the coronavirus this was relatively simple – it is the protein spikes which cover the surface of the virus and are easy to identify. To continue the cake decoration analogy scientists knew from very early on that they needed a particular colour of sprinkle for their COVID-19 vaccine to work. If you went shopping for their cake topping in the supermarket you knew you had to buy “red sprinkles” - it would be an easy task, you knew exactly what to buy.
Unfortunately it is less straightforward with most other viruses. It is not obvious which part of their structure the vaccine should be targeted against. It is like being told to go to the supermarket but this time to buy “a decoration for a cake” but you have no idea whether it’s sprinkles, nuts, chocolate, sweets etc. You have to buy everything, and try everything, until the cake finally meets with approval. It takes longer, costs more and there will be a lot of wastage but you don't have to bake the whole cake from scratch.
Advancements in technology will also affect how vaccines are stored and given. Most vaccines have to be kept refrigerated, some at extremely low temperatures. Pfizer’s COVID-19 vaccine has to be stored at -70’C making it impossible to use in the poorer and/or more remote parts of the world that don’t have electricity.
The reason why vaccines have to be stored like this is to keep them stable. They start to degenerate if stored at ambient temperatures. One hope is that new vaccine technologies will also lead to more stable, easy to store vaccines and therefore make them more user-friendly to distribute.
Some vaccines may no longer even need to be given by injection. There is already a flu vaccine used in children that is given as a nasal spray. In theory vaccines for viruses that cause respiratory infections may work better if they could be delivered directly into the lungs, perhaps by inhalation. Different methods of administration is another area scientists are now exploring.
Which diseases could be tackled next?
There are many diseases that have the potential to cause a pandemic of the future including Ebola, Zika, and plague.
It is tempting to think of plague as something assigned to medieval history but sporadic outbreaks of bubonic plague still occur every year with the most recent one in China in 2020. (4)
The Oxford team have already started clinical trials of a vaccine for plague and Moderna is analysing how to use its COVID-19 vaccine technology to develop other vaccines for a variety of diseases including plague.
Some diseases will prove much harder to develop a vaccine for than others. The HIV virus for example is constantly mutating and alters its appearance so much that the immune system can’t easily recognise it. BioNTech are in the initial stages of looking into whether the technology behind their COVID-19 vaccine, the Pfizer vaccine, could be used to develop an HIV vaccine.
The roll out of the first ever malaria vaccine last month was a significant milestone in the fight against this disease but it is only around 30% effective because the malaria parasites keep changing and evading both drugs and vaccines. Scientists are continuing to work on malaria vaccines in the hope of producing one that will be at least 75% effective. (5)
Why is improving vaccine technology so critical?
Both new diseases, such as COVID-19, and recurring diseases such as flu, Ebola and plague have been responsible for millions of deaths throughout history.
Until recently the one thing that helped prevent mass transmission of disease was the fact that there was very little international travel. However, this changed rapidly during the 20th century.
The Spanish flu pandemic of 1918-1920 killed over 50 million people worldwide. A large proportion of the deaths occurred in the three months after the end of World War 1 when the mass movement of soldiers returning home allowed the virus to spread across borders. (6)
Human behaviour has changed enormously over the past 100 years. We live in increasingly dense urban areas and frequent, international travel for business and leisure has become the norm. This means that many infectious diseases now have a way to spread around the world more quickly and easily than ever before. Whilst many of these diseases may originate in the poorer nations of the world, the richer ones cannot be complacent and consider themselves immune. If COVID-19 has taught us anything it is that viruses do not care about borders, they will take hold and spread wherever they can.
Vaccines must be prioritised in the low- and middle-income countries both for the benefit of the people of those places and for the world as a whole. Only the equitable distribution of vaccines will lead to ultimate success in disease control. Current events do not auger well on that score. Despite many promises that the COVID-19 vaccines would be fairly distributed, the reality is that the wealthier nations have had by far the greater share. If this remains the case with future vaccines, then we will continue to have outbreak after outbreak of preventable diseases. (7)
Well known diseases are getting a stronger grip on the world.
For example, dengue fever was once only seen in Thailand and the Philippines but is now found in Latin America, South East Asia, India, Africa, Australia and the Pacific Islands. Rates are highest in the major cities of the developing world primarily because of the combination of poor sanitation and overcrowding. Cases of dengue fever have been increasing over recent years and the WHO (World Health Organisation) is closely monitoring outbreaks as it becomes an increasing global health threat. The one dengue fever vaccine currently available can only be used in people with confirmed previous dengue virus infection and not in children or travellers at all. This vaccine was the centre of controversy in 2017 when it was rolled out to children in The Philippines despite a lack of trial data to support its safety. The vaccine contributed to the deaths of some of the children who received it and an enquiry found that its roll out had been rushed such was the desperation to have a vaccine against this deadly disease. (8)
Cholera continues to cause hundreds of thousands of deaths every year. The older injectable vaccine has become ineffective and there is now an oral vaccine given as two doses no more than six weeks part – but protection lasts just six months or less. A better, more effective and long lasting vaccine for cholera is desperately needed.
Typhoid is an infection of the bowel caused by a bacteria called Salmonella typhi. As its name suggests this bacteria is related to the one that causes salmonella food poisoning. The WHO estimates that there are around 17 million cases of typhoid worldwide each year. It is widespread throughout Africa, Asia and South America. The infection can quickly spread throughout the body and is fatal in up to 30% of untreated cases. Typhoid is treated with antibiotics but some strains of typhoid are now resistant to all antibiotics and of particular concern is that this resistant strain has emerged in densely populated areas in both Asia and South America.
The current typhoid vaccines do work against the antibiotic resistant strain but none of them can be given to children aged under 2 yet they are amongst the most vulnerable to typhoid infection. (9)
Development of a typhoid vaccine that can be given to babies and very young children is urgently needed to help control the inevitable typhoid outbreaks that continue to occur.
In Conclusion
There is much to be learned from the COVID-19 pandemic, not least in the field of vaccine development. International travel and an ever-increasing world population provide ideal means and opportunity for infectious diseases to spread. Future pandemics are a certainty, not a possibility.
The COVID-19 pandemic has accelerated new technologies in the world of vaccine development opening up the possibility of producing vaccines against a whole host of infectious diseases, many of which have the potential to cause future pandemics.
Vaccines are without doubt the most effective way to control infectious disease outbreaks and the rapid development of the COVID-19 vaccines shows what science can achieve. However, alongside this lessons must be learnt from episodes such as the dengue fever vaccine controversy of 2017 - as vaccine research and development accelerates it needs to be as flawless and irreproachable as possible.
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