The lead candidate malaria vaccine (RTS,S/AS01E) provides young African children with sustained protection against malaria for at least 15 months after vaccination, making it a very promising public-health intervention with the potential to save hundreds of thousands of lives, according to an Article published Online First in The Lancet Infectious Diseases.
The RTS,S/AS01E vaccine was developed for use in Africa where malaria kills nearly 900, 000 people a year, mainly young children under the age of five. The RTS,S/AS01E vaccine works by attacking the malaria parasite in its early stages, when it first enters the bloodstream or liver cells, with the aim of completely preventing infection of red blood cells (erythrocytes) and the development of serious symptoms.
A phase 2 study was established to assess the safety and efficacy of the RTS,S/AS01E malaria vaccine against Plasmodium falciparum infection in healthy African children in malaria endemic areas. Between March 2007 and October 2008, 894 children aged 5 months from Kenya and Tanzania were randomly assigned to three doses of either RTS,S/AS01E (447 children) or rabies vaccine (447). Blood samples were taken before vaccination and at regular intervals during the trial to test for antibodies.
In 2008, initial results showed that the RTS,S/AS01E vaccine gave 53% protection against clinical malaria for at least 8 months.
In this study, Ally Olotu from the Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya, and colleagues followed-up the children for a further 7 months. A modelling analysis was also done to examine associations between levels of anti-circumsporozoite antibodies and vaccine efficacy*.
In the longer-term, the efficacy of the vaccine did not wane and protection against clinical malaria lasted for at least 15 months after vaccination.
After 15 months, children vaccinated with RTS,S/AS01E were 45.8% less likely to be infected with the P falciparum parasite.
Frequent serious adverse events included pneumonia, febrile convulsion, gasteroenteritis, and P falciparum malaria. However, fewer serious adverse events were reported in the RTS,S/AS01E group (11.4%) than in the rabies group (19.7%).
The modelling analysis showed that an antibody concentration in the range of 35 EU/mL provided the best distinction between those children who were vulnerable to infection and those who were not.
The authors say: "Further studies are needed to establish vaccine efficacy in, for example, children with HIV infection or those who are malnourished. Furthermore, phase 3 studies should include study sites at different transmission intensities to confirm how generalisable our results are."
They conclude: "RTS,S/AS01E confers sustained efficacy for at least 15 months and shows promise as a potential public health intervention against childhood malaria in malaria endemic countries."
In a Comment, Brian Greenwood from the London School of Hygiene and Tropical Medicine, London, UK, discusses how the lack of an immunological measurement to reliably predict protection against malaria infection has hindered vaccine development.
However, he concludes: "The need for such a correlate will become less if the [ongoing] phase 3 trial of the RTS,S/AS01 confirms the promise shown in…[this] study done in Kenya and Tanzania, and RTS,S/AS01 becomes the first malaria vaccine to be licensed and widely deployed."
Dr Ally Olotu, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya. T) +254 728 999 263 E) firstname.lastname@example.org
Or Justa Wawira, Communications Officer, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya. T) +254 733 853887 (mobile)
Professor Brian Greenwood, London School of Hygiene and Tropical Medicine, London, UK. T) +44 (0)207 431 0743 E) email@example.com
The Lancet Infectious Diseases