The vaccine has been more than three decades in the making, with scientists from drugs company GSK creating it in 1987.
Initial trial of what has been called the world's first malaria vaccine to give partial protection to children is set to begin in Malawi.
Earlier, smaller trials showed that nearly 40% of the 5-to-17-month-olds who received it were protected.
The RTSS vaccine trains the immune system to attack the malaria parasite, which is spread by mosquito bites.
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.
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.
BBC reports that 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.