October 31 2011
Alexey Underwood examines the breakthrough and speaks to the head of charity Malaria No More UK
A successful conclusion to the battle against malaria could soon be within reach, recent clinical trial results of an experimental vaccine have suggested.
The vaccine candidate developed by GlaxoSmithKline (GSK) has been shown to halve the chances of infants experiencing malaria in a large-scale Phase III clinical trial carried out across Sub-Saharan Africa, where the deadly disease is endemic.
The sensational data was presented simultaneously in the New England Journal of Medicine (NEJM) and at the Bill & Melinda Gates Malaria Forum in Seattle and reveals that GSK’s 30-year push to develop a malaria vaccine may be finally reaching fruition.
The drug, known as RTS,S or Mosquirix, would make history if it were to enter the market as the world’s first effective malaria vaccine.
A vaccine couldn’t really arrive at a better time – although the World Health Organization has recently reported that malaria-related deaths have fallen by 20% worldwide, the disease still threatens half of the world’s population.
gair rhydd was able to exclusively speak to Sarah Kline, executive director of Malaria No More UK – a leading charity that has helped save over 5 million lives and aims to help reduce malaria-related deaths to near zero by 2015.
Freshly returned from the Bill & Melinda Gates Malaria Forum, she reminded us that “malaria continues to kill 781,000 people each year – many are young children and pregnant women”. She carried on to hail RTS,S as a “huge scientific achievement” and added that “for the 225 million who contract malaria every year, it could be a life saver”.
Malaria can be classified into two forms: clinical and severe. Clinical malaria is characterised by fever-like symptoms; if untreated, it can lead to severe malaria and its associated deadly effects on the brain, blood and kidneys.
Malaria is caused by Plasmodium parasites infecting and replicating within red blood cells – with Plasmodium falciparum being the deadliest of them all. The parasites are carried within the saliva of mosquitoes – most commonly those of the Anopheles genus.
Mosquitoes flush saliva into their victim through their proboscises – it acts as an anticoagulant and prevents blood clotting around the wound. This way, mosquitoes can feed on a constant stream of blood until they are satisfied.
However, the Plasmodium remain and travel to the liver to mature and replicate – where they are unnoticeable to the immune system. Once mature, the parasites migrate to the red blood cells and replicate within them, again bypassing the immune system.
Because malaria is spread by mosquitoes, current prevention methods mainly revolve around the usage of insecticide sprays and treated bed-nets. These methods alone have proven to be reasonably effective – a recent large-scale implementation of such products in 40 countries has managed to cut malaria deaths by half.
GSK aims to change this. Three simple injections of its RTS,S drug was shown to reduce the chance of children aged 5-17 months experiencing clinical malaria by 56% and severe malaria by 47% over the following 12-month period. This suggests that the vaccine, if used in conjunction with the traditional malaria prevention methods, could significantly reduce the risk of contracting malaria.
RTS,S is not the first experimental malaria vaccine to be trialled. Like most traditional vaccines, they tried to destroy the pathogens as soon as they entered the bloodstream – in the case of malaria, as soon as the Plasmodium were injected into the blood with insectile saliva.
Such vaccine candidates had only minutes to work before the Plasmodium reached the liver for the next stage of their life cycle – after which the pathogens would reside either in hepatic or red blood cells, undetectable to immune cells.
For this reason many scientists have long thought a fully functional malaria vaccine would be impossible to create, and clearly the researchers at GSK had to try a radically different approach. RTS,S works by exploiting our innate cellular immunity.
The drug utilizes T-lymphocytes – immune system cells – that can identify cells infected with the parasite, regardless of whether they are in the bloodstream or in the liver, initiating an immune response. This contrasts with the traditional model of a vaccine, which creates antibodies capable solely of killing off loose pathogens in the bloodstream and other body cavities.
For this to happen, a T-cell response to the malarial Plasmodium would have to be stimulated, which called for adjuvants to be used – substances which indirectly increase the efficacy of a drug or vaccine. The adjuvant contained within RTS,S is the immune-boosting QS-21 Stimulon, a plant derivative developed by Agenus. The compound potentiates the immune response and is currently also being used in the development by GSK of shingles and non-small cell lung cancer vaccines, currently undergoing clinical trials.
The actual clinical trial of RTS,S is perhaps as revolutionary as the drug itself – it is the largest-scale trial to ever be carried out in Africa, with 15,460 children and infants being experimentally immunised across 11 sites in Sub-Saharan Africa. The ground-breaking statistics recently published are derived from the analysis of the final stage Phase III data of 6,000 5-17-month-olds.
This data set, which shows that three injections of RTS,S halve the risk of experiencing malaria over a 12-month follow up period, is the first of three to be released – with the drug’s effect on newborn babies expected in 2012 and the long-term of the efficacy of the drug to be known in 2014. The World Health Organization has advised that it would be prepared to recommend the use of the drug from 2015 onwards if the trial results are satisfactory.
However, it is important to bear in mind that RTS,S is in no way a “silver bullet” – a term that has been bandied around lately in discussions regarding the drug. On the contrary, there are a number of underlying complications that need to be addressed appropriately before the drug is made available to the public.
First of all, the jab is relatively ineffective for a vaccine, reducing the risk of contracting severe malaria by a meagre 47% – by comparison, influenza vaccines are at least 75% effective.
“There are already conversations about the potential need for a booster,” said Sarah Kline of the issue, “how many times the vaccine will need to be administered, and where it will be most cost effective and able to be administered”. She went on to add that there was a “need to wait for the final trial results in 2014 before we can confidently conclude its likely final scope and scale.”
Also of concern is the side-effect profile of the drug – although the serious side-effect prevalence was not significantly larger than that of the control group, the RTS,S side-effects were particularly violent, including meningitis and seizures. GSK have suggested that the side-effects are due to various external factors – and no doubt these issues will be further investigated.
Furthermore, the drug doesn’t eliminate the chances of experiencing malaria – in many cases it simply reduces the severity of the disease, as opposed to offering complete protection from it.
Sarah Kline emphasised the importance of alternative forms of treatments, saying “we also need to track the development of other candidate vaccines; along with the ongoing development of better tools to prevent, diagnose and treat malaria”.
Without a doubt GSK has ushered in a new chapter in the research and development of vaccines, using methods and techniques that were previously thought impossible.
Regardless of whether RTS,S is quite the “miracle drug” some tout it to be, it is a testament to human resilience and determination – and most certainly a step in the right direction, from where modern science can only go forwards.
Malaria No More UK and the Global Poverty Project will be giving a presentation next month at Cardiff University, hosted by People and Planet and Engineers Without Borders.
The presentation will be held in the main building on November 14 at 7.30pm.
For more details and to sign up, visit: http://bit.ly/v2mKHZ