Since the beginning of civilisation, trees and plants have been the source of many medicinal remedies, preparations and potions. Aspirin from willow, analgesics from poppies, even chemotherapies from yew and periwinkle.
As scientists are learning, more of these ancient approaches can lead to life saving discoveries, as evidenced by one of this year’s Nobel prize winners: a Chinese scientist who recognised the potential of wormwood for treating malaria.
But these discoveries are not just limited to potential treatments. Trees are also helping researchers find new ways to develop vaccines to prevent diseases and make existing vaccines more effective and longer-lasting. This is opening up exciting new avenues for vaccine research.
One such advance uses an extract from the soap bark tree, commonly found in Chile. This tough, drought-proof evergreen has a long history of medicinal use by the Andean people. They used extracts of the inner bark for various ailments, including chest conditions, as well as for washing – hence the ‘soap’ in soap tree.
When extracted and purified, a compound from the tree’s bark, known as QS-21, can be mixed with other ingredients to create an ‘adjuvant’. The adjuvant is added to the antigen in vaccines to turbo-charge the body’s immune defences. This increases their ability to sense pathogens, alerts the immune system to their presence. The result is an increased speed and magnitude with the response.
This adjuvant approach is unlocking the potential for breakthroughs in vaccination for diseases where targeting the pathogen (whether bacteria, virus or parasite) with an antigen alone is not enough. Along the way, it is also helping us learn more about how the immune system works.
Dr Moncef Slaoui, Chairman of our vaccines business said: “GSK has invested in adjuvant research to help tackle hard-to-develop vaccines since 1989. This focus has helped us identify the potential benefits of certain compounds like the soap bark tree extract. Adjuvants have helped us go beyond a single disease itself or even the target population to find better solutions."
For example, this approach helped us discover that the adjuvant used in our malaria vaccine – for infants and babies – would also be the best tool to boost the ageing immune response of the elderly in our shingles candidate vaccine.
Most vaccines use a version of a virus or bacteria that has been altered to ensure that it doesn't trigger the disease itself but can provoke an immune response, by weakening, inactivating or using only part of the pathogen. An adjuvant is often needed to ensure that strong enough protection is achieved. This is the case for a number of widely used vaccines for diseases such as diphtheria, tetanus, polio, pneumonia or hepatitis.
This year, the world’s first vaccine against malaria, RTS,S, received a positive scientific opinion from European regulators for use in babies and children in Africa. Not only was this the first vaccine for malaria but also the first against any disease caused by a parasite.
The battle to develop a vaccine effective against the malaria parasite has been waged by scientists for decades. This microscopic enemy has proved particularly hard to tackle. It not only transforms its complex genetic makeup and its appearance as it passes through the body, but it also quickly goes to ‘hide’ in the liver where it’s hard to get at, foxing the immune system at every turn.
GSK scientists, including Dr Slaoui, realised that designing a vaccine for malaria required first helping the immune system to recognise the parasite so it could mount a defence. For RTS,S, a portion of the parasite main surface protein was fused to something more recognisable, in this case a hepatitis B virus surface protein. The hypothesis is that this would help to stimulate the immune system to fight off infection by the malaria parasite in the blood. Crucially, they also identified that the soap tree-derived adjuvant, developed by Agenus – a biotechnology company focused on developing immunotherapies – could activate T-cells to go after the parasite in the liver and boost the overall immune response.
The experience gained from RTS,S is now lending itself to other vaccines, for example GSK’s shingles candidate vaccine. Shingles is a painful and debilitating disease that can be experienced by anyone who has had chickenpox and has the herpes zoster virus lying dormant in their nerve cells. Typically it affects older people the most.
For years, the wisdom has been that achieving high levels of effectiveness is harder in older people whose immune systems may be less reactive. But with the use of an adjuvant system, an unparalleled level of effectiveness has been shown. This opens the way for high efficacy vaccines against other infections that impact older people or those with weakened immune responses.
The soap tree has been around for millennia, but we are only now realising the potential of the compounds contained within its bark. Although vaccines are the oldest medical intervention, they represent one of the most vibrant and innovative research fields of our time. This adjuvant approach is heralding the way for a new wave of vaccine breakthroughs, changing the boundaries of what was previously possible, with profound implications for human health.