RTS,S; the world’s first malaria vaccine?

According to the World Health Organisation, each year malaria causes an estimated 660,000 deaths worldwide, mostly in Africa, where one child dies of malaria each minute. At present, there is no available vaccine, only preventative measures such as mosquito nets and insecticides which have limited use. In a considerable step forward towards the fight against malaria, British drug firm GlaxoSmithKline (GSK) made headline news earlier this month with the announcement that they are seeking regulatory approval for the world’s first malaria vaccine; RTS,S. Whilst there are some other malaria vaccines in development, RTS,S is the most advanced vaccine targeting Plasmodium falciparum, the most deadly malaria parasite. Understandably, this news generated substantial excitement worldwide, however critics have raised concerns about the efficacy of RTS,S which according to trials so far, is only between 30-60%. This means that RTS,S may be useful in the prevention of malaria in some children, but it may have no effect on others. As yet, little is known about why some children are more receptive to RTS,S than others, nor how we can differentiate between those children more receptive than others.

In a recent study published in BMC MedicinePhilip Bejon and colleagues from the University of Oxford analysed Phase II trial data from two RTS,S trial sites to investigate whether peripheral blood monocyte-to-lymphocyte ratios (ML ratio) affected the efficacy of RTS,S among trial participants. This study identified for the first time that ML ratio could be used to identify children most susceptible to the RTS,S vaccine. This finding could also be used to help target future research towards identifying potential mechanisms for low efficacy of RTS,S, in patients with high ML ratio, which may well hold the key for improving overall efficacy of RTS,S.

On efficacy, Sir Andrew Witty, CEO of GSK, commented that:

“while we have seen some decline in vaccine efficacy over time, the sheer number of children affected by malaria means that the number of cases of the disease the vaccine can help prevent is impressive”.

GSK’s announcement to seek regulatory approval of RTS,S despite it’s known limitations in efficacy are in line with a goal of the Malaria Vaccine Technology Roadmap which is to ‘develop and licence a first generation malaria vaccine that has protective efficacy of more than 50%’.

In an opinion article published this week in BMC MedicineFreya Fowkes and colleagues from the Burnet Institute discuss the implications of the licensure of a partially efficacious malaria vaccine with regards to the development of a second generation vaccine. The article discusses the potential advances a second generation vaccine may have; would the second generation vaccine be more efficacious? Or would the second generation vaccine be similar to the first but perhaps cheaper,  easier to administer, have a longer duration, or target additional malaria parasites? Each of these potential advances poses unique methodological challenges with regards to the design of clinical trials for second generation vaccines which are discussed within the article.

In response to the announcement from GSK, Freya Fowkes commented:

“the announcement that GSK is seeking licensure of the first generation malaria vaccine is a landmark step in our quest for a malaria vaccine. However it is important that the licensure of a partially efficacious malaria vaccine does not slow down development of more efficacious second generation vaccines and vaccines against vivax malaria.

We eagerly await the outcome of GSK’s attempt to gain approval of RTS,S. Given the recent progress into the development of malaria vaccines, we hope the next few years will provide key advances in significantly reducing the death toll caused by malaria.

Written by Jo Denyer, Assistant Editor, BioMed Central

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