ERC grant to improve post-vaccination protection in low-income countries

Maria Yazdanbakhsh, Professor of Parasitology at the Leiden University Medical Centre (LUMC), has been awarded an ERC Advanced Grant of 2.5 million euros. She will investigate why people in Africa and Southeast Asia respond less to certain vaccines than Europeans. Her goal is to find a solution for low vaccine responses.

“New malaria vaccine studies in Europe and the United States show protection of almost 100% amongst participants. However, if we repeat this study in Africa – where the vaccine is most needed – we only see protection in 30% of the participants,” says Maria Yazdanbakhsh , Spinoza Laureate 2021 and head of the Department of Parasitology. This phenomenon is known as hypo-responsiveness and occurs with several vaccines, such as those against Ebola, Rotavirus and Yellow Fever.

Differences in immunity

With the ERC grant, Yazdanbakhsh and colleagues want to unravel the cause of hypo-responsiveness. “We know that the immune system of people in high-, low- and middle-income countries differs. But even within a single country, such as Indonesia, we see differences between people living in rural or urban areas.” These differences in the immune system are caused by environmental factors and, according to Yazdanbakhsh, underlie low protection after vaccination.

To determine exactly which differences cause hypo-responsiveness, the Spinoza laureate will combine several research methods. She will look at the immune system in the blood, as well as locally within our organs. “From the removed tonsils of people in Europe, Indonesia and a number of African countries, we will make small functional organs in the laboratory. These are so-called organoids. By combining this with the latest techniques, such as mass cytometry, omics and single cell technology1, we can study in detail how the immune system reacts to a vaccine.”

Activating the immune system

Next, Yazdanbakhsh will examine whether there are drugs in the market that can reverse the immune response differences. As an example, Yazdanbakhsh mentions checkpoint inhibitors, which are given to cancer patients alongside immunotherapy. “Tumours suppress their own immune system. Checkpoint inhibitors remove this blockade and ensure that the own immune system can fight the tumour actively again. We will investigate whether these inhibitors are also effective in the context of a vaccine.”

Simultaneous to this research, Yazdanbakhsh wants to set-up clinical studies together with other vaccine researchers. “By anticipating our results from the laboratory, we can start research in humans more quickly.” She hopes to test the first combinations of vaccines and drugs in people in Africa within five years. “What we ultimately want to know is whether this provides better protection than vaccination alone.”

Sustainable global collaborations

Within the ERC project, Yazdanbakhsh is working closely with scientists from countries such as Gabon, Senegal, Uganda, Tanzania and Indonesia. Throughout her career, Yazdanbakhsh has invested in sustainable collaborations with these countries by training local researchers. “Good collaborations in these countries is crucial for this ERC project to succeed and for the full potential of vaccines to be realised worldwide.”

ERC Advanced Grants are awarded annually to established research leaders with an outstanding record of scientific achievement.

(1) Omics is a research technique in which large numbers of molecules are measured at the same time in order to identify relevant ones from a vast amount of data. With the single-cell technology, different parts of cells, such as the genome and energy management, can be studied at the level of a single cell.

Source: LUMC

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