When a biotech company called Sanaria presented the results of a clinical study of its vaccine against unconventional malaria last year many researchers have been disappointed. The vaccine, the only one that uses the body of mosquitoes as bioreactors, were fully protected only two of the 44 volunteers from malaria.
But a new animal study shows that the vaccine is most effective when administered intravenously rather than in the skin, as it was in the clinical trial. The results give hope that the vaccine may have a future after all, but they could also complicate a possible deployment in developing countries.
There are no approved vaccines against malaria. The results of a large phase III study in seven African countries, which used a vaccine based on a protein fragment from Plasmodium falciparum , the malaria parasite, will be published before the end of 'year. The vaccine, called RTS, S and produced by GlaxoSmithKline, provided protection of 50% to 60% in previous studies; although it could make a major dent in malaria deaths, researchers hope something much better in the long term.
The vaccine Sanaria is 0% protection or even higher, said CEO Stephen Hoffman, a former researcher for the US Navy who started the company in his kitchen there 8 years. Past results suggest that this goal is possible, he said. There decades, Hoffman and other researchers found that people are almost completely protected after being bitten by hundreds of mosquitoes carrying parasites of malaria inactivated by radiation.
Apparently, a vaccine made from parasites called sporozoites-cells when they re to this point, triggers an immune response to a vaccine containing a fragment of a protein or protein one can not, the scientists concluded. Studies have suggested that sporozoites to achieve this level of protection by enabling so-called CD8 + T cells that secrete a molecule called interferon γ in the liver.
But vaccination of fixing mosquitoes lose is not practical. Therefore Sanaria's vaccine production by mosquitoes breed, infect, then meticulously cut their salivary glands. Sporozoites cells are then purified and stored in liquid nitrogen to make the vaccine.
Sanaria had hoped that intradermal injection of the vaccine would be sufficient to trigger the protection, said Hoffman. But the results of the clinical trial, first presented at a meeting there a year ago, showed that the vaccine failed to raise a CD8 + adequate response, and only two people protected. "It was not what we expected," says Hoffman.
But he was not ready to give up. He teamed with Robert Seder of the Vaccine Research Center (VCR) at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and scientists in other labs to test immune responses to the vaccine in animals. When the team injected the vaccine into the skin macaque monkeys, the reaction was similar to that of humans, but when injected into the bloodstream, the vaccine gave a strong and lasting CD8 + response in the three animals studied .
macaques may not be infected Plasmodium falciparum , but when the researchers repeated the experiment in mice, using a mouse model of malaria, they discovered that they could reach levels of protection between 71% and 100% using intravenous administration. The difference with the injection into the skin is "staggering," says Hoffman. "It was an 'aha' moment," Seder adds
A new clinical trial in which the vaccine will be administered intravenously to 51 volunteers is scheduled to begin next month in VCR. Another trial in Tanzania on the drawing board. Since animal data, "there is a good chance that it will work," said Brian Greenwood, a malaria researcher at the London School of Hygiene & Tropical Medicine.
But intravenous will pose new problems, he warns. Although intravenous vaccine will be great for travelers or Western soldiers, giving injections safely will be a challenge in poor countries where trained health workers are scarce, especially in small children whose veins are hard to find. "This is quite tricky," says Greenwood Seder says that there may be alternatives;. For example, intradermal administration may work better when coupled with compounds stimulate the immune system called adjuvants [
staff production-labor Sanaria the vaccine can take apart about 100 mosquitoes an hour could pose another obstacle. "If you talk to people in a large pharmaceutical company about it, they say you're nuts, "said Seder. But Hoffman said that these problems can be overcome. It is exploring ways to automate the process, and Sanaria can move its production facilities to developing countries where the vaccine could be produced at lower cost because labor costs are lower. "Our goal has always been to show that the vaccine is very protective," he said. "Once we did, we will understand how to make it practical."
[9/8/11, 6:47 p.m. EDT] This article has been corrected. He first said that 2 of 80 volunteers were protected against malaria. However, the 80 study participants who received the experimental vaccine, only 44 were then exposed to the malaria parasite.
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