A malaria vaccine created by scientists at the University of Oxford’s Jenner Institute has been found to be 77% effective in early-stage trials.
The vaccine – developed by the same lab that worked on AstraZeneca’s Covid-19 vaccine – represents a new hope in the global fight against malaria, a mosquito-borne parasitic disease that kills more than 400,000 people each year, mostly children in Sub-Saharan Africa.
The Phase IIb trial of the vaccine candidate, R21, enrolled 450 children in Burkina Faso, one of the 10 countries with the highest cases of malaria and subsequent deaths.
The vaccine candidate was developed in collaboration with Novavax and the Serum Institute of India (SII). The jab is being hailed as a potential breakthrough and has shown efficacy of 77% over a follow-up period of 12 months.
R21 is the first malaria vaccine to meet and exceed the World Health Organization’s (WHO) vaccine target of 75% efficacy against the deadly disease. A more extensive Phase III trial is now underway involving 4,800 children aged 5-36 months in four countries.
“These significant results support our high expectations for the potential of this vaccine, which included reaching the WHO-stated goal for a malaria vaccine with at least 75% efficacy,” said Jenner Institute director Adrian Hill.
“With the commitment by our commercial partner, Serum Institute of India, to manufacture at least 200 million doses annually in the coming years, we believe this vaccine could have a major public health impact.”
Encouraging Phase IIb results from Burkina Faso
The randomised, controlled, double-blind trial was conducted at the Clinical Research Unit of Nanoro (CRUN) / Institut de Recherche en Sciences de la Santé (IRSS), Burkina Faso.
The 450 children were recruited from the catchment area of Nanoro, a setting with particularly high seasonal malaria transmission.
In the three-armed study, children aged 5-17 months received 5 mg of R21 with either 25 mg or 50 mg of Novavax’s Matrix-M, or a rabies vaccine as a control. The researchers reported a vaccine efficacy of 77% in the higher adjuvant dose group and 71% in the lower adjuvant dose group.
Each child received three doses spaced a month apart, from May 2019 to August 2019 to coincide with the peak of malaria season in Burkina Faso.
A preprint of the study’s findings was published in The Lancet and reports that both adjuvant dosage levels were well tolerated in young children with no reported severe reactions to the vaccine. Additionally, participants vaccinated with R21/Matrix-M showed high titers of malaria-specific anti-NANP antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose.
Although antibody levels declined over time, a fourth dose given one year later boosted antibodies to levels similar to the peak titers achieved following the primary series of vaccinations.
Vaccine safety, immunogenicity and efficacy in participants will continue to be assessed for another 12 months.
The holy grail of malaria research
Malaria is a dangerous illness caused by a parasite that is carried by mosquitos and transmitted to humans via mosquito bites. The disease, which particularly plagues developing countries, starts off with flu-like symptoms such as fever, shaking-chills, headaches and muscle aches, can quickly spiral into severe illness and in many cases, death.
The WHO estimates there were 229 million cases worldwide in 2019 and 409,000 deaths.
The quest to find an effective and safe vaccine against plasmodium falciparum, the parasite that causes cerebral malaria, has been ongoing since 1907 and dubbed the holy grail of malaria research.
Progress has been slow and peppered only by humble wins.
GSK’s malaria vaccine Mosquirix was found to be only partially effective after four doses, preventing 39% of malaria cases and 29% of severe malaria cases among small children in Africa over four years. This vaccine is currently being piloted in Kenya, Ghana and Malawi.
Interventions such as bed nets, insecticides and anti-malaria drugs have proven helpful – though costly – in controlling the disease, but a truly effective vaccine has the potential to be a total game-changer.
As it has done during the Covid-19 pandemic, the Jenner Institute is considering applying for emergency use approval for R21. “I’m making the argument as forcefully as I can, that because malaria kills a lot more people than Covid in Africa, you should think about emergency-use authorisation for a malaria vaccine for use in Africa. And that’s never been done before,” Hill told The Guardian.
“They did Covid in months – why shouldn’t they do malaria in a similar length of time as the health problem is an even greater scale in Africa?” he said.
The trials of the Oxford malaria vaccine kicked off in May 2019 before Covid-19 became pharma’s overwhelming focus.
Creating a malaria vaccine has proven to be far more of a challenge than producing one against the coronavirus and has taken much longer due to the thousands of genes in malaria compared to only around 15 in coronavirus. Additionally, malaria requires a much more robust immune response to fight off.
R21: planning for a global vaccination drive
The Oxford vaccine will be manufactured on a large scale and at low cost by SII, which is also involved in manufacturing the Oxford/AZ Covid-19 vaccine. The malaria vaccine uses Novavax’s Matrix-M adjuvant to enhance the elicited immune system response.
“The team at Novavax is gratified to be a part of the collaboration that has led to today’s important advance for this longstanding global health problem,” said Novavax R&D president, Gregory Glenn.
“Novavax’ Matrix-M adjuvant used with the Oxford R21 antigen both minimises the dose required and thereby increases the number of doses available, and stimulates a highly effective immune response that could protect the world’s most vulnerable population, children.”
Despite having to delay supplies of the AZ Covid-19 vaccine to the rest of the world due to the catastrophic rise in cases in India, SII’s chairman and managing director Dr Cyrus Poonawalla said the institute was “excited to be working with Oxford University and Novavax on the successful development of a malaria vaccine”, and that it was “committed to supplying 200 million doses of the vaccine annually after licensure at a very cost-effective price”.
Before reaching the inevitable challenges of manufacturing and distribution, the promising Phase IIb results for R21 will have to be confirmed in a larger Phase III trial, which is currently recruiting across four countries in Africa. If the vaccine programme can replicate its performance and safety profile in a larger patient population, it brings the exciting prospect of a powerful new prophylactic tool in the global effort to eradicate one of the world’s deadliest and most persistent infectious diseases.