Image: The RTS,S vaccine being measured in the implementation trial in Malawi. Source: WHO.
The World Health Organization's recommendation of the RTS,S malaria vaccine for children at risk represents a significant milestone in the global effort to eliminate one of the world's most devastating diseases.
Burnet Malaria Immunity and Vaccines Group researcher, Dr Liriye Kurtovic spoke about the significance of this, what it means for malaria research, and how work led at Burnet is contributing to malaria vaccine development.
What is the recommendation?
On 6 October 2021 the World Health Organization (WHO) announced that for the first time it would recommend the use of the RTS,S/AS01 (RTS,S) vaccine to protect children against malaria.
"When we think about severe and fatal forms of disease it's young children under the age of five who are affected, and two thirds of the malaria deaths are kids in this age group," Dr Kurtovic said.
More than 260,000 African children under the age of five years die from malaria each year. The recommendation of the RTS,S vaccine, therefore, is aimed at protecting those most at-risk of severe illness and death.
The WHO recommends that the RTS,S vaccine be used for the prevention of Plasmodium falciparum malaria in children living in regions with moderate to high transmission.
It recommends the vaccine be provided in a schedule of four doses to children from five months of age to reduce malaria disease and burden.
Why has WHO recommended RTS,S?
Dr Kurtovic said the recommendation came after results from a pilot implementation of children in Kenya, Ghana and Malawi, running since 2019.
"This involved over 800,000 children from three different countries who were given four doses of RTS,S. The results indicated that the vaccine was safe, efficacious against severe disease, the four doses was feasible to deliver and it was accepted," she said.
The trials were funded by Gavi, the Vaccine Alliance, the Global Fund to Fight AIDS, Tuberculosis and Malaria and Unitaid, who together contributed nearly USD$70 million
What is the significance of this?
This is the first time the WHO has recommended widespread use of a vaccine for malaria.
Dr Kurtovic said the RTS,S vaccine development commenced in the 1980s.
"This has been a long, long journey ultimately leading to the vaccine that we have today, which is RTS,S, given with the AS01 Adjuvant," she said.
"The vaccine construct has been somewhat modified over time; it's been further refined. The adjuvant that it's given with has also somewhat changed over time - the adjuvant is there to boost the immune response."
"There's also been efforts to try and work out what the best dosing and scheduling is."
"And this has all been happening through a series of phase one, two, and three clinical trials performed in a number of different populations, including adults, children, and even infants as young as six weeks of age."
Image: RTS,S vaccination in Ghana. Source: WHO
Why has it taken so long to develop an effective malaria vaccine?
Dr Kurtovic said the complexity of the malaria-causing parasite- compared to other pathogens such as SARS-CoV-2 - slows vaccine development.
"The parasite has very, very distinct parasite forms. All of these are very morphologically different. They infect different cells, they express different proteins, it's almost as though we have three pathogens in one," she said.
The RTS,S vaccine targets Plasmodium falciparum which is the most common malaria species in Africa. However, P. vivax malaria is a significant problem in Asia-Pacific and South America.
"To add to that the malaria parasite has over 5000 genes. It makes a lot of different proteins that could be targeted by an immune response. We've got a really tough job to pick what is the best protein, to then base a vaccine on that's going to be effective."
"To further complicate the situation, the parasite is also genetically diverse."
"Different variants of these proteins or different strains can also impact how well a vaccine is going to perform. This is true for malaria and many infectious diseases. So once we've found what a good protein is to then go ahead and make our vaccine, that process of refinement is also incredibly extensive."
What's next? How is Burnet contributing to vaccine research?
While RTS,S in its current form is a good vaccine, its efficacy is modest when compared to other vaccines such as the suite of COVID-19 vaccines available.
Dr Kurtovic said this means a 'vaccines-plus' approach is needed, where other interventions such as insecticide-treated bed nets are used to control malaria.
"Efficacy is only about 30 to 50 per cent. But for a disease that has such a large burden, that can still make a significant difference, especially when it's used in combination with other interventions," she said.
"RTS,S is an imperfect tool. In our lab, we're really interested in understanding how the vaccine works. We know it induces antibodies, but we want to know how they function."
Burnet's Malaria Immunity and Vaccines Group, led by Professor James Beeson, is working to understand how vaccines generate protective and long-lasting immunity against malaria.
Dr Kurtovic said gaining a greater understanding of this would allow researchers to examine ways of modifying the current vaccine to make it more efficacious.
"We still have quite a bit of work to go but I'm very, very positive for the next steps," she said.
