A large-scale trial of what has been called the world's first malaria vaccine to give partial protection to children is due to start in Malawi.
The RTS,S vaccine trains the immune system to attack the malaria parasite, which is spread by mosquito bites.
Earlier, smaller trials showed that nearly 40% of the 5-to-17-month-olds who received it were protected.
Malaria cases appear to be on the rise again after a decade of success in combating the deadly disease.
According to the most recent annual figures, global malaria cases are no longer falling, sparking concerns about its resurgence.
More than 90% of both those who were infected and the 435,000 who died were in Africa. Children are particularly vulnerable.
Malawi saw nearly five million confirmed cases in 2017 and it has been chosen, along with Kenya and Ghana, to be used in the large-scale pilot of the RTS,S vaccine.
The countries were picked because they already run large programmes to tackle malaria, including the use of bed nets, yet still have high numbers of cases.
The vaccine has been more than three decades in the making, with scientists from drugs company GSK creating it in 1987.
Years of testing supported by a host of organisations, including the Path Malaria Vaccine Initiative, and costing an estimated $1bn (£770m) have led to this point.
This latest phase is being co-ordinated by the World Health Organization (WHO), which says the vaccine is the first to provide some protection to children.
The nearly 40% efficacy is not high in comparison with vaccines for other diseases, but the WHO says RTS,S will add to the preventative measures, such as bed nets and insecticides, already being used, AFP news agency reports.
"A vaccine that is highly efficacious, 90% or so, that's not in view at this point," the WHO's Mary Hamel is quoted by Bloomberg as saying. "But this vaccine getting to where it is shows that a malaria vaccine can be made. It will be a pathfinder."
The vaccine needs to be given four times - once a month for three months and then a fourth dose 18 months later.
This stage of the trial is expected to be completed by 2023, according to Path.
The pilot begins in Malawi and will start in Kenya and Ghana in the coming weeks.