Much excitement has greeted the publication of a major study which shows that RTS,S – a vaccine developed by GlaxoSmithKline – halved the risk of malaria.
The first results of the largest-ever malaria vaccine study have been published in the New England Journal of Medicine and were announced at the Malaria Forum hosted by the Bill & Melinda Gates Foundation in Seattle. The trial, conducted at 11 sites in seven countries across sub-Saharan Africa, showed that three doses of RTS,S reduced the risk of children experiencing clinical malaria and severe malaria by 56% and 47%, respectively.
This analysis was performed on data from the first 6,000 children aged five to 17 months, over a 12-month period following vaccination. The trial is ongoing and efficacy and safety results in six to 12 week-old infants are expected by the end of 2012, though an analysis of severe malaria episodes so far reported in all 15,460 infants and children enrolled in the trial at six weeks to 17 months showed 35% efficacy over a follow-up period ranging between 0 and 22 months (average 11.5 months).
Seizures and meningitis higher with RTS,S
The data did demonstrate differences in rates of serious adverse events such as seizures and meningitis, which were higher in the malaria vaccine group. However the researchers noted that the seizures were considered to be related to fever and the meningitis cases were unlikely to be vaccine-related. Further information about the longer-term protective effects of the vaccine, 30 months after the third dose, should be available by the end of 2014.
The vaccine, which was invented, developed and manufactured at GSK Biologicals’ headquarters in Belgium in the late 1980s, is being developed in partnership with the PATH Malaria Vaccine Initiative (MVI), which gets major funding from the Gates Foundation. GSK has invested more than $300 million to date into RTS,S and expects to spend another $50-100 million before the completion of the project.
Tsiri Agbenyega of the Agogo Presbyterian Hospital in Ghana and a principal investigator of the trial, said that having worked in malaria research for more than 25 years, “I can attest to how difficult making progress against this disease has been. Sadly, many have resigned themselves to malaria being a fact of life in Africa”. However, he added that “this need not be the case” and “renewed interest in malaria by the international community, and scientific evidence such as that we are reporting today, should bring new hope that malaria can be controlled.”
On ‘cusp of having the world’s first malaria vaccine’
GSK chief executive Andrew Witty said that “these data bring us to the cusp of having the world’s first malaria vaccine, which has the potential to significantly improve the outlook for children living in malaria endemic regions across Africa”. He added that the addition of a malaria vaccine to bed nets and insecticide spraying “could potentially help prevent millions of cases of this debilitating disease”.
Mr Witty went on to say that “development is however only half the task, but GSK remains committed to…ensuring that this vaccine will reach those who need it.” In January, he announced that the eventual price of RTS,S will cover the cost of manufacturing the vaccine together with a small return that will be reinvested in R&D for second-generation malaria vaccines or vaccines against other neglected tropical diseases.
Reaction to the trial has been pretty positive. In an editorial in the NEJM, Nicholas White of the Faculty of Tropical Medicine, Mahidol University, Bangkok, said “it’s been a long time coming, and indeed we are still not there yet, but it is becoming increasingly clear that we really do have the first effective vaccine against a parasitic disease in humans”.
Trial published ‘with less than half efficacy results’
He does have reservations, noting that “it is not usual practice to publish the results of trials in pieces, and there does not seem to be a clear scientific reason why this trial has been reported with less than half the efficacy results available”. Prof White added that “the target population for this vaccine is young infants who would receive the malaria vaccine together with routine immunisations, but the critical efficacy results in this subgroup will not be reported for another year”. Even then, “only results on short-term efficacy will be available, findings that will be insufficient to assess the public health role of this vaccine”.
He also expressed concern about the significantly more cases of meningitis among children receiving RTS,S than among those receiving the comparator vaccines. “There seems to be no plausible explanation for this, and it may well turn out to be a chance finding”, he said, “but it cannot be ignored”, while the increased risk of seizures “may be real, reflecting the reactogenicity of this highly immunogenic vaccine”.
Prof White concluded by saying the investigators “who have laboured long and hard in the development and evaluation of this malaria vaccine deserve congratulations”. He said “it is a great achievement and an important advance, but they know that this partially protective vaccine is not the sole solution to the control and elimination of malaria”.
