Developers of the world's first candidate malaria vaccine said that new tests have shown that it protects a third of six- to 12-week-old infants, which is less than its effect in older babies.
The "modest" result came as a surprise to researchers working hard on a drug to combat the mosquito-born disease that kills hundreds of thousands of children per year.
The trial vaccine, RTS,S, is made by British pharmaceutical giant GlaxoSmithKline, whose chief executive officer Andrew Witty called the result "a little frustrating".
"We... would have liked to have seen higher efficacy than we have of course," he told a telephone press conference of the Phase III trial results published in the New England Journal of Medicine.
But he stressed that "this is not a mission we should just walk away from. This remains the lead and still the most encouraging (malaria) candidate vaccine."
A year ago, the RTS,S team announced that the candidate drug cut risk in African children between the ages of five and 17 months in half over a period of 12 months.
The biggest trial of its kind, under way at 11 sites in seven African countries, seeks to block the parasite that causes malaria.
The disease kills an estimated 655,000 people every year, mainly children under five living in sub-Saharan Africa.
Dr Salim Abdulla, who leads the trial in Tanzania, said three doses of the drug had reduced clinical malaria in the younger children by 31 percent, and severe malaria by 37 percent.
For the older group, the figures had been 55 percent and 47 percent respectively.
"We will continue to examine the different factors that may be behind the different levels of efficacy," Abdulla said.
The researchers expect to have final trial results by 2014, including the vaccine's efficacy over 30 months after administration, and the effects of a later, booster dose.
Abdulla said the positives include confirmation that the vaccine is safe and that it can be administered with other childhood vaccinations without any worrying side-effects.
"The efficacy came back lower than we had hoped, but developing a vaccine against a parasite is a very hard thing to do," said Bill Gates, co-founder of the Bill & Melinda Gates Foundation which sponsors the trial.
"The trial is continuing and we look forward to getting more data to help determine whether and how to deploy this vaccine."