The Hitchhiker’s Guide to the Galaxy says 42 is the answer. But what is the question?

For Professor Faith Osier it is: What are the parasite proteins that trigger immunity to malaria?

It’s well known that malaria kills, on a massive scale. But surprising numbers of people actually survive infection – and go on to become resistant. Understanding why, says Professor Faith Osier, Co-Director of Imperial’s Institute of Infection, could be the key to the eradication of the disease.

“How some people with malaria parasites present in their blood are able to live entirely unaffected by the disease, while others fall desperately ill or die, is a mystery yet to be solved,” says Osier. “And the reason we still don’t know the answer is that the malaria parasite has got thousands of proteins.” To give a sense of the scale of the challenge, the virus that causes COVID-19 has fewer than 30.

Osier has been exploring this issue on a molecular level for the past 20 years, attempting to isolate which parasite protein, or proteins, trigger the immune response. “We know that people can become immune because we’ve been studying immune responses in the population for a long time. But whatever the magic bullet is, it’s concealed in a sea of other bullets.”

The last decade has seen a major advance: challenge trials, in which consenting participants are infected with a well-understood, easily treatable strain of malaria and watched to see how their immune systems respond. Compared to studying malaria in the community, explains Osier, challenge trials make it “much easier to say who became sick as a result of this infection and who didn’t”. By analysing blood samples from the participants, her team has been able to significantly narrow down which of the parasite proteins may be responsible for disease.

The next, and hopefully final, step will be a further challenge trial, one that involves vaccinating participants before infecting them. Such a study could be just three years away, with results available two weeks following infection. “That is where my work must go for me to close the loop and retire in peace,” says Osier.

Professor Faith Osier is Co-Director of Imperial’s Institute of Infection and President of the International Union of Immunological Societies.