This malaria vaccine is delivered by a mosquito bite

Scientists have developed a new vaccination strategy for malaria — boosting immunity through bites from genetically engineered mosquitoes. The immunization is delivered through insects infected with modified versions of the parasite that causes malaria. In a trial, the approach reduced participants’ susceptibility to malaria, potentially paving the way for more effective ways to stop the disease, which infects some 250 million people a year.

“These findings represent a significant step forward in malaria vaccine development,” says Julius Hafalla, an immunologist at the London School of Hygiene & Tropical Medicine. “The ongoing global malaria burden makes the development of more effective vaccines a critical priority.”

The study, which was published¹ in The New England Journal of Medicine on 20 November, exposed participants to bites from mosquitoes that had a modified version of the Plasmodium falciparum parasite, which causes malaria. In humans, the parasites travel to the liver and then infect red blood cells. The parasites were engineered to stop developing shortly after delivery into a human. Nearly 90% of participants exposed to the modified parasites avoided contracting the disease after being bitten by malaria mosquitoes.

There are two approved malaria vaccines. Both aim to provide long-term immunity by producing antibodies that block malaria parasites from infecting liver cells, as well as targeting breakthrough infections.

But the vaccines are only about 75% effective, and require booster shots. So immunologists are continuing to explore alternative strategies.

One approach is using genetically modified parasites. The research team had previously trialled the effectiveness of a modified malaria parasite, called GA1, that is designed to stop developing about 24 hours after infection in humans². But the GA1 parasite protected only a few participants against malaria, leading the team to engineer a second parasite, GA2. GA2 is designed to stop developing about six days post-infection, during the crucial period where the parasites replicate in human liver cells.

The researchers tested whether exposure to GA1 or GA2 could help humans develop immunity to malaria. They exposed participants to bites from 50 mosquitoes; 10 participants received bites from mosquitoes infected with GA1 parasites, and 10 were bitten by those with GA2 parasites. Three weeks later, they exposed participants to malaria-carrying mosquitoes. Just before exposure to these mosquitoes, both sets of participants had higher levels of antibodies than before. One of eight (13%) participants bitten by GA1 parasites didn’t contract malaria compared with 89% in the GA2 group. Other than the the itching associated with mosquito bites, side effects were limited.

The researchers are now keen to replicate their results in a larger trial.

The work “should be followed by more extensive studies to confirm GA2’s viability as a candidate for global malaria control”, says Hafalla.