Following the successful rollout of a Malaria Vaccine, scientists are now testing the efficacy of a vaccine that protects travelers against malaria in other groups first.
This also comes in the wake of field trials in older age groups – including people who are thinking of becoming pregnant – are in the works, while vaccines against other types of malaria are also under development.
Although the focus is still on people who live in malaria-endemic countries for now, a travel vaccine could become available in the coming years, researchers say.
If travellers can afford to go to Africa, they can generally afford to buy antimalarial drugs and take them prophylactically, which they already should be doing,” said Professor Adrian Hill, chief investigator of the R21/Matrix-M programme and director of the Jenner Institute at the University of Oxford.
Both the RTS,S and R21 vaccines are designed to protect people against Plasmodium falciparum, the deadliest species of malaria parasite. The World Health Organization (WHO) has initially recommended both vaccines for the prevention of malaria in children, with the first of four doses given from around five months of age.
This doesn’t mean these vaccines won’t be effective in other age groups, but young children have been prioritised in the initial clinical trials because they are at greatest risk of severe forms of malaria and death. African countries have also taken precedence because 93% of deaths from malaria occur here and P. falciparum is the dominant species of malaria-causing parasite in the African Region.
Even so, people who have had no earlier exposure to malaria – including travellers from non-endemic countries – are also at risk of the most severe forms of malaria. So, could they also benefit from these vaccines, once further doses become available?
Having a vaccine would probably be useful, although these aren’t the only way of preventing infection, says Professor Adrian Hill, chief investigator of the R21/Matrix-M programme and director of the Jenner Institute at the University of Oxford.
Even children who have been vaccinated are advised to take additional precautions to prevent malaria, such as sleeping under bednets and taking antimalarial drugs at specific times throughout the year. And as Hill points out: “If travellers can afford to go to Africa, they can generally afford to buy antimalarial drugs and take them prophylactically, which they already should be doing.”
While malaria vaccines may eventually become available to travellers, he says trials in other groups are higher priority – including older children and adults living in countries where malaria is endemic.
There is already reason to believe that the current vaccines may be effective in these groups. A standard part of the process for developing a vaccine for children involves testing it in adults first. “Researchers then work through age groups to ultimately reach children with the appropriate dose,” said a spokesperson for GSK, the company behind the RTS,S malaria vaccine.
Indeed, a key breakthrough in the development of RTS,S came in 1996, when a study showed that the vaccine protected six out seven adult volunteers who were bitten by infected mosquitoes in a laboratory. A later Phase 2 trial in the Gambia, which involved vaccinating 360 men who’d previously been exposed to malaria with three doses of RTS,S, also found that the vaccine was well-tolerated, and had a strong protective effect during the first nine weeks, although this quickly waned. Later trials introduced a fourth dose for this reason, including trials in children.
In the next few months, two trials will begin administering the R21 vaccine to thousands of people of all ages across Bangladesh, The Gambia and Burkina Faso to investigate whether expanding vaccination to these groups could help to eliminate P. falciparum malaria in these countries, in combination with antimalarial drugs and other measures. “We will be trying to knock out malaria in the population by protecting everybody,” says Hill.
Another important question is whether existing vaccine malaria vaccines could help to protect people who are intending to become pregnant, because catching malaria during pregnancy not only puts people’s lives at risk, but it can also affect the growth and survival of the foetus. A separate trial assessing the efficacy of R21 vaccine in preconception people is expected to begin later this year in Mali.
While many existing travel vaccines afford a high degree of protection after just one or two doses, R21 and RTS,S are given as three or four doses, and further precautions against malaria would still be needed, which might be off-putting for casual travellers.
Assuming the vaccines are effective in adults, regulators might consider approving their use for travellers or military troops deployed to countries where P. falciparum malaria is endemic. But while many existing travel vaccines afford a high degree of protection after just one or two doses, R21 and RTS,S are given as three or four doses, and further precautions against malaria would still be needed, which might be off-putting for casual travellers.
Existing vaccines also don’t protect against other species of Plasmodium, including P. vivax, the dominant malaria parasite in most countries outside sub-Saharan Africa. P. vivax malaria is also transmitted from person to person by mosquitoes, and a single infection can result in repeated and severe disease episodes, but P. vivax is only weakly related to P. falciparum, so a different vaccine is needed.
Efforts to develop such a vaccine are ongoing. One of the most advanced candidates targets the P. Vivax version of the same protein as the RTS,S and R21 vaccines: the circumsporozoite protein (CSP) found on the surface of Plasmodium parasites when they’re in the sporozoite form, which is how they enter the human body. Phase 1 trials of this vaccine candidate are expected to begin soon.
GSK said that, while they were developing products targeting both P. falciparum and P. vivax, their vaccine focus remains on P. falciparum, for now. “At this point in time our focus for RTS,S is ensuring its successful roll-out, transferring the technology know-how to Bharat [a biotechnology company based in Hyderabad, India, which is taking over manufacturing of the RTS,S antigen] to significantly increase supply in the medium term, and understanding if there are ways that implementation can be optimised,” a spokesperson said.
After decades of false starts, the roll-out of malaria vaccines in children is cause for great excitement. Trials in older age groups may further turn the tide against malaria, and pave the way for a travel vaccine. But for now, the best protection for travellers remains avoiding mosquito bites and taking prophylactic drugs.