The vaccine candidate, R21, has been developed by the University of Oxford in collaboration with the Serum Institute of India, using Novavax’ Matrix-M adjuvant.
The phase 2b study included 450 children aged 5-17 months in Burkina Faso. A Phase 3 clinical trial has now begun in 4,800 participants aged 5-36 months.
Many malaria vaccine candidates - but only one that reaches WHO goals
There were an estimated 229 million cases of malaria worldwide in 2019, with an estimated 409,000 deaths, according to WHO figures. Children under the age of five are the most vulnerable, accounting for 67% of deaths.
The development of an efficacious vaccines against Plasmodium falciparum has remained elusive for a number of decades. While more than 100 vaccine candidates have entered clinical trials, none had reached the 75% efficacy goal set by the WHO in its roadmap to tackle malaria.
The most effective malaria vaccine candidate to date is RTS,S/AS01 – GlaxoSmithKline’s Mosquirix – which started pilot vaccination in Africa in 2019 (Phase 3 trials reported 55.8% efficacy over the first year, dropping to 36.3% over a median of 48 months follow up).
The Oxford malaria vaccine, however, is the first to reach the WHO's target, demonstrating 77% efficacy (over 12 months of follow-up).
In the Phase 2b trial, participants were split into three groups: with the first two groups receiving the malaria vaccine (with either a low dose or high dose of the Matrix-M adjuvant) and a third control group (rabies vaccine). Doses were administered from early May 2019 to early August 2019, largely prior to the peak malaria season.
The researchers report a vaccine efficacy of 77% in the higher-dose adjuvant group, and 71% in the lower dose adjuvant group, with no serious adverse events related to the vaccine noted.
“This new vaccine, R21 76 adjuvanted with 50 µg Matrix-M (R21/MM), administered prior to the malaria season, demonstrates high-level 77% efficacy: reaching the WHO-specified efficacy goal of ≥75% in the target population of African children over one year,” notes the pre-print study in The Lancet.
“Furthermore, R21/MM demonstrates a favorable safety profile: it is well- tolerated with the majority of local and systemic adverse events graded mild, and no serious adverse events (SAEs) related to vaccination in the trial.
"Importantly, while this vaccine immunogen is similar to RTS,S, it lacks the excess HBsAg found in RTS,S and 81 provides a higher density of CS epitopes on the particle surface, resulting in high levels of malaria-specific anti82 NANP antibodies. These were effectively boosted one year later to levels similar to those after the primary series of vaccinations.”
In addition, the vaccine has the potential for large-scale manufacturing and low-cost supply, add researchers.
“The R21 paediatric dose is 5µg, compared to 25µg for RTS,S, and the former is manufactured using a high-yielding process by the Serum Institute of India Private Ltd., the largest supplier of low-cost vaccines globally.
"The saponin adjuvant, Matrix-M, lacks the monophosphoryl lipid A (MPL) adjuvant component which is found in AS01 and requires a separate manufacturing process. So, Matrix-M is less complex to manufacture than AS01 further enabling large scale and lower cost supply of R21/MM.
"These factors contribute to the future potential of R21/MM as a vaccine in countries where malaria is a major public health concern.”
The Phase 2b trial will continue to assess longer term efficacy: with a booster prior to the following malaria season.
The Matrix-M component of the malaria vaccine will be manufactured and supplied to SII by Novavax. Under Novavax' agreement with Serum Institute, SII has rights to use Matrix-M in the vaccine in regions where the disease is endemic and will pay Novavax royalties on its market sales of the vaccine. Additionally, Novavax will have commercial rights to sell and distribute the SII-manufactured vaccine in certain countries, primarily in the travelers' and military vaccine markets.
Novavax’s Matrix-M adjuvant is also being used in the company's COVID-19 vaccine candidate.