A jab, then protection (Image: Frederic Courbet/Bill & Melinda Gates Foundation)

Encouraging results from the longest and largest trial of a malaria vaccine could see the world’s first anti-malaria jab approved by 2015. The disease infects more than 200 million people a year, and kills at least 660,000 – mostly children. The vaccine could be used for the first time in 2016.

“It’s on that trajectory, and the plan is to file with the European Medicines Agency in 2014,” says David Kaslow, vice president of product development at the PATH Malaria Vaccine Initiative, which supported development of the vaccine, made by GlaxoSmithKline (GSK).

A positive scientific verdict from the European agency, expected in 2015, would pave the way for African countries to approve it for use by 2016, says Kaslow, who presented the results in Durban, South Africa, at a major international conference on malaria.


Called RTS,S, the vaccine was tested in 15,000 children in 11 African trial sites. Half were babies aged 6 to 12 weeks and the other half toddlers aged 5 to 17 months. Half in each group received the vaccine and half a placebo, and all continued where possible with other precautions to prevent malaria such as sleeping under bed nets.

The latest data show that eighteen months into the trial, the vaccine continued to work best in the older age group, echoing results seen one year after the trial started.

Efficiency issues

At that one year mark, there were 56 per cent fewer cases in the older group and 31 per cent fewer cases in the younger group. The new data show that the vaccine’s effectiveness waned slightly after 18 months: there were 46 per cent fewer cases of clinical malaria in the older age group, and 27 per cent fewer cases in the younger group.

“We expected this,” says Kaslow. “Efficacy wanes for most vaccines, which is why, for example, we give booster shots for tetanus.”

Kaslow says that boosters have already been given at 20 months to see if they revive the original efficacy of the vaccine.

“One-third of the children in the trial have now received a booster dose, so we’ll learn in the next year if this protects the children for a further period,” says Brian Greenwood of the London School of Hygiene and Tropical Medicine, who heard the results presented in Durban.

The older children will be followed for a total of 41 months on average, but the results after 18 months are positive enough to persuade GSK to initiate plans to submit for approval.

“While we’ve 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,” says Andrew Witty, chief executive officer of GSK.

Great potential

From the average incidence of malaria across the 11 sites, combined with the fact that single children are prone to as many as four infections a year, the researchers calculate that the jab has the potential to prevent 941 cases of malaria per 1000 children vaccinated in the older age group, and 444 in the babies.

“These data support our decision to submit a regulatory application for the vaccine candidate,” says Witty.

As to why the vaccine seems to be more effective in older children, Kaslow says there’s no explanation, but there are some possible reasons. One is that immune systems of the babies are too immature to respond to the vaccine. Another is that unlike the older recipients, they received a pentavalent vaccine at the same time against five other diseases. “It’s possible the hepatits B component of the pentavalent vaccine interfered with the malaria vaccine, but we don’t know yet,” he says. A Third reason is that there could be some interference from maternal antibodies.

Kaslow says there is also hope from other vaccines entering trials, particularly for “transmission-blocking” vaccines. These trigger production of human antibodies that block development of the malaria parasite not in humans, but in the guts of mosquitoes that have swallowed the antibodies while feeding. “It’s active vaccination of humans to produce passive vaccination of mosquitoes,” he says.

Trials also began this year of a vaccine made from live but weakened malaria parasites painstakingly extracted from the spit glands of mosquitoes. The vaccine worked extremely well in the first six recipients, and larger trials are planned.