This World Malaria Day, a University of Toronto PhD student is shedding light on a poorly understood phenomenon that could impact vaccination strategies for malaria and other infectious diseases.

The phenomenon, called vaccine-driven evolution, describes possible scenarios where immunization could drive a pathogen to become better at causing disease, for example through evading the immune system.

“I’m interested in how interventions like vaccines shape the evolution of virulence and other related parasite traits,” says Youngseo Jeong, a PhD student in the department of ecology and evolutionary biology. Specifically, she is focused on the Plasmodium family of parasites that are commonly transmitted by mosquitoes and that in humans cause the life-threatening disease malaria.

The World Health Organization estimates that globally in 2022, there were 249 million malaria cases and 608,000 malaria deaths, with the African region bearing the heaviest burden. With the approval of the world’s first malaria vaccine in 2021 and a second vaccine in 2023, vaccination programs have become an important part of the public health strategy to combat the disease.

The launch of malaria vaccination campaigns in the African region comes at a time when progress against the disease has stalled and two of the most important tools to prevent and treat malaria are losing their effectiveness. Insecticide-treated bed nets, a mainstay to prevent mosquito bites and kill mosquitoes, offer less protection as mosquitoes become increasingly resistant to the insecticides. Similarly, clinicians are concerned that the spread of Plasmodium parasites resistant to frontline antimalarial drugs will hamper their ability to treat the disease.

Both of these challenges arose as a result of mosquito and parasite evolution in response to a human intervention. Whether a malaria vaccination program could lead to similar changes in the Plasmodium parasite is a key question in the field and one that Jeong aims to answer through her work with Nicole Mideo, an associate professor of ecology and evolutionary biology in U of T’s Faculty of Arts and Science.

With the support of a Doctoral Award from the Emerging and Pandemic Infections Consortium, she is applying mathematical approaches to study how parasites evolve in hosts who have been vaccinated versus hosts who have not.

Jeong’s research, which is based on a mouse model of malaria, builds on a 2012 study from American researchers that found Plasmodium parasites caused more severe disease after repeated infections of vaccinated mice. Surprisingly, the researchers did not find any changes to the part of the parasite targeted by the vaccine — a common process by which pathogens evade vaccine-induced immunity — and the cause of the parasite’s increased virulence remains unknown.

To identify the specific traits that are responsible for the parasite’s enhanced abilities, Jeong is using a mathematical model of malaria infection fitted with data from the 2012 study. She will determine which parameters, or parasite traits, in her model can explain the differences between parasites that evolved in vaccinated and unvaccinated hosts.

In the second phase of her PhD project, Jeong will refine the model by including relevant biological processes like vaccine-induced immunity and the specific parasite characteristics she identified earlier. She will also create a new mathematical model to simulate evolution in a vaccinated host and validate her earlier findings.

“I want to highlight not just evolution at the vaccine target sites, which receives more attention generally, but I also want to draw attention to other pathogen traits and their interactions with host processes that could have consequences for how effective the vaccines are,” says Jeong.

She hopes that her work will contribute to a better understanding of how vaccine-driven evolution in parasites can lead to more severe infection outcomes in both vaccinated and unvaccinated individuals, and underscore the importance of considering this phenomenon when designing new malaria vaccines and immunization programs.

By Betty Zou