Scientists say if it was rolled out on a large scale it could save hundreds of thousands of lives.
Malawi will on Tuesday spearhead large scale pilot tests for the world's most advanced experimental malaria vaccine in a bid to prevent the disease that kills hundreds of thousands across Africa each year.
After more than three decades in development and almost US$1 billion in investment, the cutting-edge trial will be rolled out in Malawi's capital Lilongwe this week and then in Kenya and Ghana next week.
It aims to immunise 120,000 children aged two years and under to assess the effectiveness of the pilot vaccine and whether the delivery process is feasible.
Four successive doses must be administered on a strict timetable for it to work.
Trade-named Mosquirix, the drug has been developed by British pharmaceutical giant GlaxoSmithKline in partnership with the PATH Malaria Vaccine Initiative.
It passed previous scientific testing - including five years of clinical trials on 15,000 people in seven countries - and was approved for the pilot programme in 2015.
Malaria episodes reduced by 40 percent in the trials.
Although the potential vaccine will not give full protection against the mosquito-borne disease, it is the furthest along in development and so far the most effective.
The World Health Organization (WHO) believes that the new vaccine brings a key new tool beyond mosquito nets, insecticides and drugs in the battle against the disease.
Malaria killed 435,000 people in 2017. The majority of them were children under five in Africa.
"Malaria can kill a child in less than 24 hours," said researcher Tisungane Mvalo, a paediatrician at University of North Carolina at Chapel Hill Project-Malawi in Lilongwe.
"And even if the child survives, malaria can impact every organ, causing brain injury or even kidney issues. Prevention is better than treatment.
WHO's latest report on malaria showed that the number of cases climbed to 219 million in 2017, two million higher than 2016.
"Despite gains over the last decade, we have seen a stagnation in malaria control efforts in recent years," said researcher Jonathan Juliano from the University of North Carolina.
"In certain areas of Africa, we have actually seen rates of malaria infection get worse. New interventions are needed to continue advancing toward elimination."
The fight against malaria has also been complicated by mosquitoes building up resistance to some commonly used insecticides, according to WHO.
Malawi, Ghana and Kenya were selected for the trial because malaria rates are high and they have a long history of use of bed nets and other interventions.
The large-scale pilot is the latest step in decades of work seeking to eradicate malaria.
Despite concerns over recent rises in malaria cases, the numbers dying from the disease has fallen nearly two-thirds since the turn of the century.