After years of disappointing malaria vaccine trials, a malaria shot developed by researchers at the Jenner Institute at the University of Oxford has demonstrated an unprecedentedly high efficacy of 77 percent, and may be the magic bullet the world has been waiting for against the deadly disease.
The results come from a Phase II trial of the vaccine, called R21/Matrix-M (MM), which have been published in a pre-print study in the journal The Lancet.
The news is certainly a bright spot on World Malaria Day, celebrated on April 25. The theme of World Malaria Day 2021 was “Reaching the zero malaria target,” which the World Health Organization (WHO) and its partners marked by celebrating the achievements of countries that are approaching and achieving malaria elimination.
Oxford’s malaria vaccine trial was conducted in Burkina Faso among 450 children who were followed for 12 months. In the Lancet paper, the authors note the shot was the first to meet the WHO’s Malaria Vaccine Technology Roadmap goal of a malaria vaccine with at least 75 percent efficacy.
Adrian Hill, study co-author, director of the Jenner Institute and professor of vaccinology at the University of Oxford, said in a statement from the university, “These new results support our high expectations for the potential of this vaccine, which we believe is the first to reach the WHO’s goal of a vaccine for malaria with at least 75 percent efficacy.”
Malaria is a life-threatening disease caused by parasites from the genus Plasmodium that are transmitted to individuals via mosquito bites. Symptoms include fever, headaches and chills and, without treatment, the infection can progress quickly to severe illness and often death.
According to the WHO, there were 229 million cases of the disease in 2019 worldwide, which claimed the lives of 409,000. The agency also says 94 percent of all malaria cases and deaths in 2019 occurred in the region of Africa.
Currently, the only other viable malaria vaccine, known as RTS,S/AS01 (Mosquirix), has a demonstrated efficacy of 55.8 percent. It is the world’s first and only licensed malaria vaccine and also the first licensed for use against a human parasitic disease of any kind. The vaccine dates back to the 1980s and was developed by SmithKline Beecham Biologicals, now GlaxoSmithKline (GSK) Vaccines. Despite its low efficacy, RTS,S was given the go ahead by the WHO in 2015 for a pilot implementation and was administered to people in Kenya and Ghana in 2019.
Given the success of Oxford’s Phase II trial, the study investigators are now gearing up for a Phase III licensure trial to assess large-scale safety and efficacy in 4,800 children aged 5 to 36 months across four countries in Africa. Children have been the focus of malaria vaccine and drug trials because over 90 percent of deaths attributable to malaria are in African children under the age of five.
Developing an efficacious vaccine against malaria has been a huge challenge. It has taken over three decades for researchers to meet the WHO’s 75 percent mark for a malaria vaccine. This compared to the current COVID-19 vaccines which were developed in under a year, with some having sky-high efficacies of 95 percent. This is because there are thousands of genes in malaria parasites compared to only about a dozen or so in coronaviruses. Moreover, a very strong immune response is needed to fend off the disease.
“That’s a real technical challenge,” said Hill, “The vast majority of vaccines haven’t worked because it’s very difficult.”
“With the commitment by our commercial partner, the Serum Institute of India, to manufacture at least 200 million doses annually in the coming years, the vaccine has the potential to have major public health impact if licensure is achieved.”
Oxford researchers developed the R21/MM malaria vaccine in collaboration with the Serum Institute of India and biotech company Novavax. The vaccine is protein-based and contains an adjuvant (MM), a component that helps generate a stronger immune response, that was developed by Novavax.
Malaria Vaccine Phase II Trial
R21/MM was evaluated in a double-blind, randomized, controlled trial in children aged 5 to 17 months in Nanoro, Burkina Faso, a setting with high seasonal malaria transmission. Three doses of the vaccine were administered at four-week intervals before the beginning of the malaria season, with a fourth dose given one year later. Vaccine safety, immunogenicity and efficacy were evaluated over the span of one year.
In the trial, 450 children were randomized to receive the R21/MM vaccine or a control rabies vaccine. A rabies vaccine is often used as a control in malaria vaccine trials to assess generation of an immune response; not many people are likely to have received a rabies shot previously and hence in unvaccinated people, it serves as a positive control for a vaccine-induced immune response. Two different doses of the adjuvant (MM) were assessed (25 mcg and 50 mcg). At six months, 29.5 percent of children who received R21/MM with low-dose adjuvant, 26 percent who received R21/MM with high-dose adjuvant and 71.4 percent who received the rabies vaccine developed clinical malaria.
Vaccine efficacy in the low-dose adjuvant group was 74 percent and 77 percent in the high-dose adjuvant group. Vaccine efficacy was sustained at one year in the high-dose adjuvant group. R21/MM vaccinated participants had high titers of malaria-specific anti-NANP antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. A fourth dose a year later boosted waning titers to the same peak levels after the initial triple-dose regimen. R21/MM was found to have a favorable safety profile and was well-tolerated.
Based on these results, the authors on the study concluded that, “R21/MM appears safe and very immunogenic in African children, and demonstrates promising high-level efficacy.”
Changing the Face of Malaria
Once the malaria vaccine is approved by regulators, The Serum Institute of India says it will be ready to deliver more than 200 million doses of the vaccine.
The trial has been funded by The European & Developing Countries Clinical Trials Partnership (EDCTP), The Wellcome Trust and the NIHR Oxford Biomedical Research Centre.
Prof Charlemagne Ouédraogo, minister of health in Burkina Faso, said the new data showed that a new malaria vaccine could be licensed in the coming years and that it “would be an extremely important new tool for controlling malaria and saving many lives.”
As one of the leading causes of childhood mortality in Africa, an effective malaria vaccine is indeed a much-needed tool to change the face of the disease and its impact on children in the continent.