An experimental malaria vaccine made of live, but irradiated parasites is safe and evokes a mild immune response, concludes an early-stage clinical trial. Yet the vaccine protected only a small fraction of people from actual malaria infection.
However, parallel work in animals suggests the vaccine may have failed because it was given to humans the wrong way. Intravenous injections in mice prompted a strong immune response and protected the rodents from malaria, paving the way for new trials in humans.
The vaccine, produced by the firm Sanaria based in Rockville, Maryland, attempts to mimic the observation that humans bitten by mosquitoes harbouring an irradiated form of the malaria parasite Plasmodium falciparum called sporozites develop long-lasting immunity to malaria, which infects 300 million people and kills one million annually. The sporozoites infect the liver and provoke an immune response, but, because of the weakening effect of the radiation, they don’t go on to infect red blood cells or cause malaria.
Led by malaria expert and former US Navy researcher Stephen Hoffman, Sanaria has spent the last decade developing the vaccine, which involves growing the parasite in millions of mosquitoes and then dissecting their salivary glands to obtain the sporozites.
As a first go, Hoffman’s team administered doses of the vaccine either intradermally or subcutaneously to 80 volunteers. Some of them developed immune responses against components of the vaccine, but only 2 of the 44 volunteers who were later exposed to malaria did not become infected. None of the volunteers developed serious side effects.
Tests in a mouse model of malaria and in rhesus macaques suggest that giving the vaccine intravenously is the way to go. Between 77 and 100% of the mice that received intravenous injections of a sporozite vaccine were protected from malaria infection. Hoffman’s team found that the virus prompted the mouse immune system to produce T-cells in their livers that churn out an infection-fighting protein called interferon-gamma. Three out of four rhesus macaques who received the vaccine intravenously developed a similar immune response, an indication that the vaccine may do the same for humans. The work appears in this week’s issue of Science.
Sanaria is planning a small trial of intravenously-injected virus for later this year. The company hopes its virus will protect more than 80% of the people who receive it for at least six months, and ideally more than two years.
Results from a phase III trial of 16,000 children of the leading malaria vaccine candidate are expected by the end of this year. But previous trials of this vaccine have suggested that the virus protects, at most, half of the infants and children who receive it.
This blog has been updated to mention experiments performed in macaques.
Image courtesy of Wikimedia Commons