IT鈥橲 going to be fiddly work, but the saliva glands of mosquitoes are to be used as mini factories for churning out a novel vaccine against malaria.
The vaccine is based on the whole parasite, rather than individual proteins, and may therefore work better than other vaccines in development because the body can mount a multi-pronged attack against it. 鈥淭hat鈥檚 the ideal,鈥� says John McNeil, scientific director of the not-for-profit Malaria Vaccine Initiative (MVI).
The mosquitoes that transmit malaria do so because they are infected with immature sporozoites of the parasite Plasmodium falciparum. These travel from the mosquitoes鈥� salivary glands into the blood of people they bite, then to the liver, where they mature, multiply and cause full-blown malaria.
Advertisement
The new vaccine will be composed of sporozoites mass-produced by feeding parasite-infected blood to mosquitoes grown in captivity 鈥� then the parasites are weakened by zapping the mosquitoes with radiation.
Although the sporozoites in the vaccine will be too weak to infect humans, they will trick the body into preparing a defence, should real malaria come along.
Such live 鈥渁ttenuated鈥� vaccines are already routinely used against bacterial and viral diseases including polio, measles and typhoid. The idea of using whole weakened P. falciparum as a vaccine against malaria was first proposed 40 years ago, but was abandoned because of problems in scaling up production to extract the weakened parasites.
In trials of the latest vaccine on 14 humans four years ago, volunteers received virtually full protection against malaria for at least 42 months, despite being repeatedly bitten by infected mosquitoes 鈥� substantially better than any other malaria vaccine yet tested. Just one vaccinated volunteer fell ill, whereas all the volunteers who were unvaccinated succumbed. They were immediately given drugs to kill the parasite.
鈥淎ll the vaccinated volunteers were fully protected from malaria for 42 months, despite being bitten repeatedly鈥�
To make a proper vaccine that can be easily stored, transported and injected, the sporozoites need to be extracted from the insects fast enough and in large enough quantities to make millions of doses of vaccine 鈥� a step thought impossible until now.
鈥淣o one argues whether a sporozoite-based vaccine would be the gold standard,鈥� says Stephen Hoffman, founder of Sanaria, a vaccine company in Rockville, Maryland, which was awarded a $29.3-million grant from MVI to develop the vaccine on 14 December. 鈥淚t鈥檚 whether the vaccine can be made.鈥�
The Sanaria team now think they鈥檝e cracked the problem. Their process relies on the fingers of skilled dissectors working around the clock to extract salivary glands from individual insects. 鈥淚t鈥檚 like a chip factory in Malaysia,鈥� says Hoffman. 鈥淲e have many nimble individuals good with their hands.鈥� Hoffman calculates that one person can extract hundreds of doses of vaccine per hour.
The vaccine is due to undergo toxicology studies next year, in preparation for trials in human volunteers in 2008.
The ones that got away
All killers leave clues, however crafty they may be, and the mosquitoes responsible for spreading malaria are no exception. Thanks to telltale trails left in the mud by the larvae of Anopheles gambiae, we now know that they can survive outside puddles sprayed with insecticide, in areas where they were thought to have been eradicated years ago.
It now seems that billions of larvae survive when the puddles dry up. 鈥淥ur new research shows that the habitat for larval A. gambiae includes the moist or wet mud around puddles,鈥� says Jim Miller, the eagle-eyed entomologist at Michigan State University in East Lansing, who spotted the trails with a magnifying glass after kneeling for hours in mud in Kenya and watching larval behaviour.
Not only can the larvae survive several metres from the sprayed puddles, but they can also wriggle back to water. 鈥淲e believe, but haven鈥檛 yet proven, that larvae can survive for several days on moist mud,鈥� Miller told 快猫短视频. From now on, he says, treatments should include mud and soil several metres from puddles. A report of the team鈥檚 work appears in Naturwissenshaften, DOI: 10.1007/s00114-0060-0178-y.
