Not so good news for adults on malaria vaccine

New findings from a study in Kenyan adults have cast doubt on the effectiveness of the RTS,S/AS01 malaria vaccine in reducing infections among African adults, raising questions about its potential role in malaria elimination strategies.

Conducted by scientists from the Kenya Medical Research Institute (Kemri), the Walter Reed Army Institute of Research, and GlaxoSmithKline, the study provides crucial insights into vaccine efficacy in populations where malaria is endemic.

The study enrolled 620 healthy Kenyan adults, divided into five groups based on the presence or absence of Plasmodium falciparum infections at the start. Participants received either RTS,S or a rabies vaccine, used as a control.

Research was carried out at the Kemri-Walter Reed Project’s Kombewa Clinical Research Center in Kisumu County, western Kenya, a region where malaria remains endemic.

Published in “The Journal of Infectious Diseases”, the findings indicate that RTS,S is unlikely to provide sufficient protection against infection in African adults to be included in malaria elimination strategies.

While RTS,S, together with its sister vaccine R21/Matrix-M, is currently recommended  by the World Health Organisation (WHO) for children living in endemic areas of sub-Saharan Africa, its efficacy in adults appears limited. Both vaccines are already being administered across several African countries with support from Gavi, the Vaccine Alliance.

Best practice

 Global best practice demands that for a vaccine to be considered effective, it would optimally provide a relatively high level of efficacy and be used in mass immunisation campaigns for all age groups.

Previous studies have shown that the efficacy of RTS,S is lower in African adults than in malaria-naïve (those who have never been infected with malaria) US adults. This may be due to concurrent P. falciparum infections in the African adults when they were vaccinated; there is some evidence that active or asymptomatic malaria infections may suppress the immune response to vaccines.

For the study participants with active Plasmodium falciparum infections, who were administered antimalarial drugs during the vaccination period, a modest level of efficacy was observed.

However, no vaccine efficacy was observed in participants who were free of protozoa infection at the study start and were also treated with antimalarial drugs.

This study highlights the importance of conducting malaria vaccine clinical trials in target populations.

The vaccine efficacy results from this study were lower than from studies where malaria-naïve adults were vaccinated and subjected to controlled human malaria infection.

“While the current study results are unable to explain why there was no efficacy in the group of participants who tested negative for P. falciparum at the study start, we believe this is a clue in our attempt to understand why susceptibility to malaria infections varies among individuals despite similar exposure to the parasite,” said Dr Cynthia Lee, the study lead and Project Director of the Bacterial & Parasitic Diseases Area at PATH’s Center for Vaccine Innovation and Access.

Even so, the vaccines remain an effective intervention for reducing child deaths and the number of times children get malaria, including severe malaria, and ongoing vaccine implementation activities should continue as planned.

Recent studies combining RTS,S with antimalarial drugs in young African children resulted in a synergistic effect in averting clinical malaria infections.

Researchers in this study tested a widely held assumption that antimalarial drugs given to adults could reverse this immunosuppression and enhance overall vaccine efficacy, and that the efficacy would be higher in RTS, S-immunised participants who tested negative for infection at the start of the study. The study results showed that these assumptions were incorrect.

“The study will inform future studies that seek to explain the efficacy of various interventions such as vaccines that are focused towards malaria elimination, and ultimately global eradication,”, said Prof. Elijah Songok, Director General, Kemri.

Malaria is a life-threatening disease caused by Plasmodium parasites, transmitted to humans by certain mosquitoes. It remains endemic in western Kenya and along the coast, posing a persistent public health challenge despite ongoing control efforts.