The vaccine, developed by GlaxoSmithKline, has been in a pilot program in Ghana, Kenya and Malawi since 2019, reaching more than 800,000 children.
Widespread use could save tens of thousands of young lives a year, according to the WHO: “The long-awaited malaria vaccine for children is a breakthrough for science, child health and malaria control,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. This is the first time the WHO has recommended a malaria vaccine for widespread use.
The R&D program for the vaccine stretches back 30 years.
'A glimmer of hope'
Malaria remains a primary cause of childhood illness and death in sub-Saharan Africa. More than 260,000 African children under the age of five die from malaria annually.
In recent years, however, the WHO and its partners have warned of stagnating progress against the deadly disease. While more than 100 vaccine candidates have entered clinical trials, reaching sufficient levels of efficacy has created a serious challenge.
"For centuries, malaria has stalked sub-Saharan Africa, causing immense personal suffering,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. “We have long hoped for an effective malaria vaccine and now for the first time ever, we have such a vaccine recommended for widespread use.
"This offers a glimmer of hope for the continent which shoulders the heaviest burden of the disease and we expect many more African children to be protected from malaria and grow into healthy adults.”
Highly cost-effective vaccine
Malaria is caused by Plasmodium parasites transmitted through the bites of infected female Anopheles mosquitoes. There are five parasite species that cause malaria in humans, with P. falciparum and P. vivax posing the greatest threat.
RTS,S acts against P. falciparum, the most deadly malaria parasite globally and the most prevalent in Africa.
In 2018, P. falciparum accounted for 99.7% of estimated malaria cases in the WHO African Region; 50% of cases in South-East Asia; 71% of cases in the Eastern Mediterranean and 65% in the Western Pacific.
P. vivax is the predominant parasite in the WHO Region of the Americas, representing 75% of malaria cases (RTS,S does not offer protection against P. vivax)
As a pre-erythrocytic vaccine, it targets P. falciparum parasites before they infect liver cells (different malaria vaccines target different stages of the parasite development).
The WHO recommends the vaccine should be used in children living in regions with moderate to high malaria transmission (as defined by the WHO). It should be provided in a schedule of four doses in children from five months old.
Findings from the pilot showed that the vaccine was feasible to deliver through routine immunizations, even in the context of the COVID-19 pandemic; and that the vaccine was ‘highly cost-effective’, according to the WHO.
A Phase 3 trial conducted from 2009 - 2014 in 15,000 young children and infants in seven sub-Saharan countries showed a four dose regiment prevented approximately 4 in 10 cases of malaria (39%) over four years of follow up.
Newer data suggests that, in combination with seasonal administration of antimalarials, the vaccine lowers clinical episodes of malaria, hospital admissions with severe malaria, and deaths by around 70%.
More than 2.3 million vaccine doses have been administered in Ghana, Kenya and Malawi since 2019.
Scaling up production and distribution
GSK is working with partners to ensure equitable and long-term access to the RTS,S vaccine according to the WHO recommendations.
30 year journey
RTS,S is the result of 30 years of R&D by GSK and a partnership with PATH, with support from a network of African research centres. The Bill & Melinda Gates Foundation provided funding for late-stage development from 2001 to 2015.
A product transfer, including technology transfer for long-term antigen production, is also underway with Bharat Biotech of India.
GSK will donate up to 10 million RTS,S doses for use in the pilots.
It will also work with partners, funders and governments to support additional supply of the vaccine, and has committed to make 15 million annual doses available at no more than 5% above cost of production.
Thomas Breuer, Chief Global Health Officer, GSK, said: “GSK is proud that RTS,S, our ground-breaking malaria vaccine, developed over decades by our teams and partners, can now be made available to children in sub-Saharan Africa and other regions with moderate to high malaria transmission.
"This long-awaited landmark decision can reinvigorate the fight against malaria in the region at a time when progress on malaria control has stalled.
"Both real world evidence and clinical trial data show that RTS,S, alongside other malaria prevention measures, has the potential to save hundreds of thousands of lives.”
Other malaria vaccine candidates
The University of Oxford, in collaboration with the Serum Institute of India, is developing a malaria vaccine candidate. The vaccine, R21, adjuvanted with 50 µg Matrix-M (R21/MM) from Novavax, recently reported 77% efficacy in children in a Phase 2b trial.
BioNTech is developing a mRNA-based malaria vaccine, hoping to reach clinical trials by 2022; while also aiming to build up vaccine manufacturing capability in Africa.