“Scientists herald early-stage clinical tests as the most promising yet in the global war on the world's biggest killer,” (malaria) is the exciting news on the Sky News website.
The story comes from a fascinating study testing an experimental malaria vaccine against Plasmodium falciparum – the most deadly of the malaria-causing parasites. Malaria is a highly infectious disease, transmitted by the bite of infected mosquitoes.
Currently there is no vaccine to prevent this deadly disease which kills over 600,000 people annually, most of them children.
Previous research has found that people who received more than 1,000 bites from irradiated mosquitoes developed some level of immunity against malaria. While using this method is obviously impracticable in a real world setting, it did give the team involved in the study the idea of using the parasites that infect mosquitoes to create a vaccine.
The study found that of 15 volunteers who were given higher doses of the new vaccine, 12 were protected against infection by the malaria parasite when exposed to bites from infected mosquitoes three weeks later.
This is a tiny, early stage study and its results need to be replicated in larger trials. Nevertheless, the results are a promising step forward in the long and often frustrating journey to developing a malaria vaccine.
The study was carried out by researchers from the National Institute of Allergy and Infectious Disease in the US. It was funded by the same institute and published in the peer-reviewed journal: Science.
The Mail Online’s headline that the vaccine had proved “100% effective”, while technically accurate, is not as impressive as it sounds. It neglected to mention that this was only the case in the six volunteers who received the highest dose of the vaccine.
Other than that, the Mail’s and the rest of the UK’s coverage was thorough, pointing out early in the story that the trial was small scale so more testing is needed.
This study was a phase I trial testing an experimental vaccine for malaria in 57 adult volunteers. Malaria is transmitted to humans in the bite(s) of mosquitoes infected with one of the malaria-causing parasites. The current study focused on malaria caused by Plasmodium falciparum parasites, which is the most severe form of malaria and can be life-threatening.
Immature P. falciparum parasites (called sporozoites) then travel to the liver where they multiply and spread through the bloodstream, at which time symptoms begin. These typically include fever and headache and in severe cases the disease progresses to cause complications such as severe anaemia and breathing problems, and may progress to coma and death.
The disease is widespread in tropical and subtropical regions. Currently no vaccine is available and travellers to malarial areas are advised to protect against mosquito bites by covering up, using mosquito nets and insect repellents, and sometimes taking preventative medication.
Five species of Plasmodium can be transmitted from mosquitoes to humans but the vast majority of deaths are caused by two of them – Plasmodium falciparum and Plasmodium vivax.
The authors point out that the World Health Organization (WHO) has set a goal to develop a vaccine with 80% efficacy by 2025 but so far, no such vaccine has been developed. They also point out that trials some 40 years ago showed that volunteers are protected against malaria after they receive more than 1,000 bites from irradiated mosquitoes carrying the Plasmodium falciparum sporozoites (exposure to radiation weakens the parasites).
The vaccine tested in this study is composed of live but weakened Plasmodium falciparum sporozoites, taken from the salivary gland of mosquitoes and weakened with radiation. Previous studies where this vaccine (called PfSPZ) was injected into the muscle showed very limited protection against malaria. Experiments in animals had suggested that the vaccine might perform better if injected directly into the vein, so the researchers wanted to test this.
From 2011 to 2012, the researchers recruited 57 healthy adult volunteers aged 18 to 45 years who had never had malaria. Of these, 40 participants received the PfSPZ vaccine and 17 did not. The vaccine was given by intravenous injection (injected into a vein).
Those who had the vaccine were split into groups who received it at different doses and using different schedules for the injections, receiving between two to six intravenous doses a month apart.
After vaccination, the participants were monitored closely for seven days and their blood taken to test for antibodies and other indications of immunity to P. falciparum.
To evaluate whether and how well the PfSPZ vaccine prevented malaria infection, each participant – vaccinated or not – was exposed to bites by five mosquitoes carrying the P. falciparum strain from which the PfSPZ vaccine was derived. This is called a controlled human malaria infection (CHMI) procedure and is a standard process in malaria vaccine trials. In participants who had been vaccinated, the exposure took place three weeks after receiving their final vaccination.
All participants were then monitored as outpatients for seven days and then admitted to a clinical unit. They stayed until the researchers could determine whether they would become infected or not. Their blood was then analysed for presence of the P. falciparum parasite, and those who were infected were treated with anti-malarial drugs to cure them of infection.
Thirty-six of the 40 participants (90%) completed their vaccination schedule. Five of the control group dropped out before the trial was completed.
The researchers found that the higher dosages of PfSPZ vaccine were associated with protection against malaria infection:
There were no severe adverse effects associated with the vaccine, and no malaria infections caused by the vaccination itself were observed.
Based on blood measurements, researchers found that participants who received a higher total dosage of PfSPZ vaccine generated more antibodies against the malaria parasite as well as more T cells. T cells are a type of immune system cell which help fight infection.
The researchers point out that the trial is a “critical first step” in the development of a successful vaccine. They also point out that the group of volunteers in which all participants were protected had a seven week interval between the fourth and fifth doses of the vaccine which may have boosted their immunity against infection.
This is a promising step in the long struggle by scientists to develop a safe and effective vaccine against P. falciparum malaria. However, this was a tiny, early stage study and more research is required to replicate the results and to look further at the potential effectiveness of different doses. It is not certain how long such a vaccine may offer protection for and also, whether it would protect against other strains than the one tested here.
Travellers to malarial areas are strongly advised to avoid mosquito bites by using insect repellent and mosquito nets, and by covering up at all times. Medication may also be advised.