Science: Holy Grail of the tropics

Malaria has confounded scientists for decades, but now there may be a vaccine that works.

At the end of a maze of corridors in an anonymous building at Leeds University is a locked door. "It's a little warm in here," says Professor Mike Hollingdale as he leads the way inside. In fact the atmosphere hits you in the face like a hot flannel, causing beads of perspiration spontaneously to erupt across your forehead.

The small, white-walled room is bare save for a sink and a couple of laboratory benches. On one bench is an array of what look like washing- up bowls, each containing a few inches of water. Inside these, swarms of brown larvae dart frantically, or cluster around pellets of dog meal. On the other bench are a pair of cages draped in white mesh. From these comes a familiar, slightly irritating high-pitched whine.

The stuffy, humid room is a mosquito hatchery. It is part of a facility - unique in this country - capable of growing cultures of Plasmodium falciparum - the most important of the four species of the Plasmodium parasite responsible for one of the world's most insidious and devastating diseases, one that kills about three million people each year, mostly children. Professor Hollingdale is on the trail of the Holy Grail of tropical medicine - the development of a malaria vaccine.

The problem of malaria is worsening, and many experts believe that the only realistic solution is the development of a vaccine. But more than two decades of apparent breakthroughs followed by disappointing setbacks have shown that the challenge is far from straightforward.

Part of the difficulty undoubtedly lies in the complex life-cycle of the parasite. P. falciparum is a single-celled organism transmitted by the female mosquito. The form of the organism when it is inside the mosquito is called the sporozoite. When an infected mosquito bites someone, it injects around 100 sporozoites into their blood.

These travel in the bloodstream until they reach the liver. Here, a special protein on the surface of the sporozoite, termed CSP, recognises that it has arrived at the liver and anchors itself to the outside of the cell. The sporozoite then crosses into the liver. Once inside the liver cell, the organism changes shape, from being long and thin to being bloated and spherical. This is termed the schizont stage, and within the schizont thousands of nuclei begin to develop. Eventually maybe 20,000 daughter parasites will form.

These are called merezoites and their sheer volume causes the liver cell to burst open, releasing them into the bloodstream. When a merezoite meets a circulating red blood cell it attaches itself to the surface and enters. Once inside it divides into 15 or 20 daughters in 48 hours. These rupture the blood cell and are released to infect new cells. It is at this stage that the symptoms of malaria appear.

Vaccines work by giving the body's immune system a "preview" of a harmful pathogen - or the relevant bit of it. This allows us to manufacture the appropriate defence hardware rapidly in the event of an invasion by the real thing.

In the early 1970s it was shown that irradiated sporozoites, created by irradiating infected mosquitoes, could confer protection. This, however, is not a feasible way of delivering mass vaccination.

"The experiments with the irradiated sporozoites told us that it is possible to develop a vaccine," says Professor Brian Greenwood, of the London School of Hygiene and Tropical Medicine, who has been involved with vaccine trials in Africa. "The problem is how to devise a simple and practical way of doing it."

In the late Eighties, a putative vaccine was developed by a Colombian scientist, Manual Patarroyo. This consisted of fragments of proteins found on the surface of the parasite artificially stitched together. Early trials suggested that the vaccine produced a high degree of protection, but later studies have cast serious doubt on its effectiveness.

A series of vaccines have been developed based on the CSP. These have given varying degrees of, usually limited, protection. A field trial in The Gambia has just been completed on the latest version of a CSP vaccine, and the results are being analysed. Altogether, says Professor Greenwood, there are about 20 candidate vaccines in development.

The Leeds laboratory is one of the few places in the world able to produce the parasite under conditions which effectively mimic what goes on in sub-Saharan Africa. The parasite is first grown in blood cultures. The infected cultures are then covered by a latex membrane to simulate human skin (condoms were used in early tests). Mosquitoes are allowed to settle on the membrane and take up the parasite. These are then removed from the mosquito's body and transferred to the cultured liver cells.

Under these controlled conditions, scientists can arrest the parasite's life-cycle at any point to scrutinise the biochemical interactions taking place - which genes are active at a given time, or which proteins are essential to a particular series of events. Professor Hollingdale's team is especially interested in a protein called LSA-1. This is a large protein secreted by the parasite as it sits in the liver cells. The protein is an antigen - it elicits an immune response - in other words it stimulates the immune defences to attack it, which makes it a good candidate for a vaccine.

LSA-1 appears to activate one particular aspect of the immune defence, T-cells. These are specialised cells that are produced by the body to seek out and destroy any of the body's cells which are infected by foreign invaders. Professor Hollingdale's team has been working with adult volunteers in Papua New Guinea. By taking samples of blood and adding LSA-1 or specific fragments of the protein, they wanted to see if T-cells were produced by the blood. "Some of the volunteers had previously built up a natural protection to malaria while others had not. The group who were protected had T-cells to LSA-1 in their blood, while the group who were not protected didn't have any. This had never previously been shown and to us strongly implicated that T-cells were important in conferring protection.

"We believe that from these studies and others that there is a strong rationale for producing a vaccine based on LSA-1," says Professor Hollingdale.

The team is looking at a variety of methods to deliver the antigen as a vaccine, and is looking for funding to begin human trials within two years. The European Union has recently earmarked a budget for malaria research and Professor Hollingdale is hoping to help set up a European network to develop a concerted research effort into the development of a vaccine.

"Europe has generated a lot of the candidates for vaccines but has not really had the capital or unity to take these into the complex areas of clinical testing," says Dr David Arnot of Edinburgh University, who has been studying the molecular biology of the malaria parasite for 20 years. "Now we have the opportunity to work in close harness, which I think is an excellent thing. I am reasonably optimistic that within 10 years of good support, and with all the groups pulling hard in a concerted effort, we have a good chance of getting something to work."

Professor Greenwood agrees on the value of a united European approach. "We have been strong on the laboratory side but not had a great presence in testing potential vaccines. Hopefully this EU initiative will go some way to bridging that gap."

As for the prospects for a vaccine, Professor Greenwood remains cautious but optimistic. "For the past 20 years people have been saying `we'll have a vaccine within five years' - and they are still saying it. My own feeling is that we are unlikely to see a dramatic breakthrough, but rather an accumulation of gradual improvements. I think it is right that we follow the diverse approaches that we are pursuing now, and hope that out of this someone will hit upon something that works."

PROMOTED VIDEO
Have you tried new the Independent Digital Edition apps?
Arts and Entertainment
Thomas carried Lady Edith over the flames in her bedroom in Downton Abbey series five

TV
Arts and Entertainment
Ben Affleck as Nick Dunne, seated next to a picture of his missing wife Amy, played by Rosamund Pike

film
Arts and Entertainment
Rachel, Chandler and Ross try to get Ross's sofa up the stairs in the famous 'Pivot!' scene

Friends 20th anniversary
Arts and Entertainment
Lena Dunham

books
Arts and Entertainment
A bit rich: Maggie Smith in Downton Abbey

There’s revolution in the air, but one lady’s not for turning

TV
Arts and Entertainment
Chloe-Jasmine Whicello impressed the judges and the audience at Wembley Arena with a sultry performance
TVReview: Who'd have known Simon was such a Roger Rabbit fan?
Arts and Entertainment
Nick Frost will star in the Doctor Who 2014 Christmas special

TV
Arts and Entertainment
A spell in the sun: Emma Stone and Colin Firth star in ‘Magic in the Moonlight’
filmReview: Magic In The Moonlight
Arts and Entertainment
Friends is celebrating its 20th anniversary this year
TV
Arts and Entertainment
Ben Whishaw is replacing Colin Firth as the voice of Paddington Bear

TV
Arts and Entertainment
Actor and director Zach Braff

TV
Arts and Entertainment
Maisie Williams plays 'bad ass' Arya Stark in Game of Thrones

TV
Arts and Entertainment
Liam Neeson said he wouldn't

TV
Arts and Entertainment

TV
Arts and Entertainment
Meera Syal was a member of the team that created Goodness Gracious Me

TV
Arts and Entertainment
The former Doctor Who actor is to play a vicar is search of a wife

film
Arts and Entertainment

music
Arts and Entertainment
Pointless host Alexander Armstrong will voice Danger Mouse on CBBC

TV
Arts and Entertainment
Pharrell dismissed the controversy surrounding

music
Arts and Entertainment
Jack Huston is the new Ben-Hur

film
Latest stories from i100
Have you tried new the Independent Digital Edition apps?

ES Rentals

    Independent Dating
    and  

    By clicking 'Search' you
    are agreeing to our
    Terms of Use.

    Syria air strikes: ‘Peace President’ Obama had to take stronger action against Isis after beheadings

    Robert Fisk on Syria air strikes

    ‘Peace President’ Obama had to take stronger action against Isis after beheadings
    Will Lindsay Lohan's West End debut be a turnaround moment for her career?

    Lindsay Lohan's West End debut

    Will this be a turnaround moment for her career?
    'The Crocodile Under the Bed': Judith Kerr's follow-up to 'The Tiger Who Came to Tea'

    The follow-up to 'The Tiger Who Came to Tea'

    Judith Kerr on what inspired her latest animal intruder - 'The Crocodile Under the Bed' - which has taken 46 years to get into print
    BBC Television Centre: A nostalgic wander through the sets, studios and ghosts of programmes past

    BBC Television Centre

    A nostalgic wander through the sets, studios and ghosts of programmes past
    Lonesome George: Custody battle in Galapagos over tortoise remains

    My George!

    Custody battle in Galapagos over tortoise remains
    10 best rucksacks for backpackers

    Pack up your troubles: 10 best rucksacks for backpackers

    Off on an intrepid trip? Experts from student trip specialists Real Gap and Quest Overseas recommend luggage for travellers on the move
    Secret politics of the weekly shop

    The politics of the weekly shop

    New app reveals political leanings of food companies
    Beam me up, Scottie!

    Beam me up, Scottie!

    Celebrity Trekkies from Alex Salmond to Barack Obama
    Beware Wet Paint: The ICA's latest ambitious exhibition

    Beware Wet Paint

    The ICA's latest ambitious exhibition
    Pink Floyd have produced some of rock's greatest ever album covers

    Pink Floyd have produced some of rock's greatest ever album covers

    Can 'The Endless River' carry on the tradition?
    Sanctuary for the suicidal

    Sanctuary for the suicidal

    One mother's story of how London charity Maytree helped her son with his depression
    A roller-coaster tale from the 'voice of a generation'

    Not That Kind of Girl:

    A roller-coaster tale from 'voice of a generation' Lena Dunham
    London is not bedlam or a cradle of vice. In fact it, as much as anywhere, deserves independence

    London is not bedlam or a cradle of vice

    In fact it, as much as anywhere, deserves independence
    Vivienne Westwood 'didn’t want' relationship with Malcolm McLaren

    Vivienne Westwood 'didn’t want' relationship with McLaren

    Designer 'felt pressured' into going out with Sex Pistols manager
    Jourdan Dunn: Model mother

    Model mother

    Jordan Dunn became one of the best-paid models in the world