Vaccine that could eradicate most deadly form of malaria by blocking parasite close to clinical trials
Oxford scientists need to raise 1million, but hope to get the vaccine to trial within two years
The experimental drug appears capable of neutralising most – or even all – strains of the parasite responsible for nine out of 10 malaria deaths
A British vaccine with the potential to eradicate the most deadly form of malaria could enter clinical trials within two years.
The experimental drug appears capable of neutralising most – or even all – strains of the parasite Plasmodium falciparum, which is responsible for nine out of 10 malaria deaths.
It works in a unique way, effectively closing the molecular door that allows the organism to invade red blood cells.
Targeting this “Achilles” heel” thwarts the parasite”s ability to dodge the immune system by evolving rapidly into new strains.
The research is published today in the journal Nature Communications.
DrSimon Draper, one of the scientists from the Jenner Institute at OxfordUniversity, said: “So far we”ve been able to knock down every strain we”ve been able to produce in the laboratory. That”s why it”s such an incredibly exciting result.
“Normally vaccines don”t work well because the parasite evolves into new strains the immune system does not recognise.
“Ifthis vaccine turns out to be highly effective in humans, as we hope, itcould be a serious contributor to an eradication programme.”
So far the vaccine, known as PfRH5, has been tested in the laboratory and on rabbits.
It was developed out of research reported last month in the journal Nature.
Scientists at the Wellcome Trust Sanger Institute in Hinxton, Cambridge, showed that P. falciparum killer parasite relies on a particular molecule, RH5, to gain access to red blood cells.
The protein RH5 latches onto a specific “receptor” molecule on the surface of blood cells which has the effect of “unlocking” a gateway for the parasite.
The new vaccine induces an immune response against RH5 to stop the lock turning and keep the door shut.
Remarkably, people naturally exposed to malaria on repeated occasions have low or undetectable levels of antibodies that act against RH5. For this reason, the scientists believe, the parasite has not been under pressure to develop strains that avoid RH5 antibodies.
“It”s a bit of a mystery,” said Dr Draper. “There are 5,000 proteins in the malaria parasite but the immune system normally ignores RH5.
“For many decades people have looked at how people develop natural immunity to malaria and said that”s what we should base our vaccines on. With the best of intentions they may have been looking in the wrong place.”
Malaria is often spread by infected mosquitos which inject parasites into the bloodstream
MALARIA FACT BOX
Malaria is a tropical disease spread by night-biting mosquitoes.
The World Health Organization (WHO) estimates that there were 243 million cases and nearly 1 million deaths from malaria in 2008.
Most deaths occur in African countries close to the equator and below the Sahara desert (Sub-Saharan Africa).
Many babies and children die from malaria. WHO estimates that a child dies of malaria every 30 seconds.
When a mosquito infected with malaria parasites (plasmodia) bites you, it injects the parasites into your body. It only takes a single mosquito bite for you to become infected.
Any type of malaria is dangerous but malaria caused by the falciparum parasite is the most serious. It can develop very rapidly and lead to severe illness and death.
The only other malaria vaccine at an advanced stage of development targets the parasite in the liver. Although currently undergoing clinical trials, it is only 30 per cent to 50 per cent effective, said Dr Draper.
He said his team was now urgently looking for funding to progress to patient trials with their vaccine.
With around 1 million, clinical trials could begin in as little as two years.
“We”re all ready to go. We can fly once we”ve got the money,” Dr Draper added.
The vaccine is injected using a harmless modified virus.
After an early safety trial involving healthy volunteers in the UK, the main trials would take place in Africa.
Co-author Dr Sandy Douglas, a Wellcome Trust Clinical Training Fellow from Oxford University, said: “We have created a vaccine that confirms the recent discovery relating to the biology of RH5, given it can generate an immune response in animal models capable of neutralising many – and potentially all – strains of the P. falciparum parasite, the deadliest species of malaria parasite.
“This is an important step towards developing a much-needed vaccine against one of the world”s major killers.”
Professor Adrian Hill, a Wellcome Trust Senior Investigator at Oxford University, said: “Vaccines against malaria are notoriously difficult to develop because the parasites” antigens – the target of vaccines – tend to be genetically so diverse. The RH5 antigen doesn”t show this diversity, making it a particularly good target for a vaccine to exploit.
“Our next step will be to begin safety tests of this vaccine. If these prove successful, we could see clinical trials in patients beginning within the next two to three years.”
The vaccine would only be effective against P. falciparum, because other species of the parasite do not employ RH5, said Dr Draper.