Excellent news today: we have word of the most effective malaria vaccine yet discovered. A year-long trial in Burkina Faso has shown 77% efficacy, which is by far the record, and which opens the way to potentially relieving a nearly incalculable burden of disease and human suffering.
This is a collaboration between the University of Oxford (Jenner Institute et al.), the KEMRI Wellcome Trust in Kenya, the London School of Hygiene and Tropical Medicine, Novavax, the Serum Institute of India, and especially the Institut de Recherche en Sciences de la Santé in Nanoro, Burkina Faso. Let’s talk about Nanoro a bit. It’s in central Burkina Faso, west/northwest of the capital Ouagadougou. Here are some shots of city, town, and rural village life in this part of the country (panel B is in Nanoro itself). The town is in a climate zone with a classic tropical pattern: hardly any rain at all in the hot season (December, January, February) and then a monsoon season in the summer and fall. That brings on masses of mosquitos, and malaria is an absolute scourge.
Past studies from the Nanoro health sciences institute make this terrifyingly clear. Here’s one where they looked a cohort of 734 infants born in the area for the first year of their lives. It’s thought that children of this age have some malaria protection due to antibodies passed on from their mothers, but as the paper says, in areas of high transmission this can be overwhelmed. In those 734 infants, they recorded 717 clinical incidents of malaria infection, with the incidence rate strongly increasing as their first year went on and the great majority of these occurring in the rainy season. This 2010-2014 study from Nanoro shows the strong correlation of local malaria cases with rainfall and temperature (with a few weeks lag, as expected), and also with socioeconomic status (in exactly the direction you’re thinking). This is the clearly the sort of region where real-world tests of a malaria vaccine need to be carried out.
This new vaccine (R21) uses a circumsporozoite protein (CSP) antigen – that’s a highly conserved protein of the parasite, involved in several functions as the parasite makes the move from mosquito to human and into different human tissues such as the salivary glands. This has been a vaccine ingredient before, such as in the RTS,S vaccine (the first one ever licensed), but R21 has a much higher proportion of CSP assembled into a virus-like particle. It also uses the exact same adjuvant from Novavax (Matrix-M) that they are using in their coronavirus vaccine – you can’t keep a good adjuvant down, and this Chilean-soapbark-based one seems to really kick the immune system up under all circumstances.
The team previously run an “age-de-escalation” trial in Kenya, showing that the vaccine seemed safe as you moved down to children and infants. That led to this trial, in 450 children aged 5 to 17 months in the Nanoro area, in three groups: 150 children with 5 micrograms vaccine and 25 micrograms adjuvant, a second 150 at 5/50, and a third getting rabies vaccine as a control. Three shots were given in the May-August period, largely before the yearly transmission period, and everyone got a booster shot one year later. The participants, their families, and the local study team were all blinded to the group assignments. Antibodies were measured at several intervals over the next year, and malaria cases were of course monitored.
The higher-adjuvant cohort showed 77% vaccine efficacy, and the lower-adjuvant one showed 74% with (as you’d expect) overlapping confidence intervals. The first group had significantly higher antibody levels, though, and they’re currently doing an additional year of follow-up to see how long the protection lasts and if these doses differentiate themselves. The antibody levels at the one-year mark in both groups were significantly higher than with the RTS,S vaccine, and in particular, antibodies against the repeat section in the middle of the circumsporozite protein seemed to correlate strongly with protection. No safety problems so far.
The team is now planning a larger Phase III at five different African site, with varying seasonality and malaria loads. The Serum Institute is manufacturing the vaccine itself, and they say that they have a large-scale production route. The Novavax adjuvant is currently in a bit shorter supply due to the coronavirus pandemic, but it’s still easier to manufacture and scale than the one used in the RTS,S vaccine. And while the dosing schedule used in this trial is a demanding one, I hope that the Phase III will help to establish the best balance between the logistics of dosing and malaria protection. Overall, this is definitely the best malaria vaccine candidate the world has yet seen, and that is unequivocal good news. Congratulations and thanks to the widespread group of researchers who have made this possible – and especially, thanks to 450 infants and toddlers in central Burkina Faso and to their parents. You have done the world a great service.
The post Great Malaria Vaccine News first appeared on In the Pipeline.
