Periodic Reporting for period 1 - REVERSE (Reversing vaccine hypo-responsiveness)
Reporting period: 2022-10-01 to 2025-03-31
Uncovering the mechanisms underlying vaccine hypo-responsiveness
There is growing evidence that vaccine immunogenicity and efficacy present considerable variations across populations in high- and low/middle-income countries. For example, the vaccination of volunteers in Europe or USA with attentuated malaria vaccine can result in 100% protection, while efficacy drops to just 29% in Africa.
Similar trends are seen with other vaccines. The EU-funded REVERSE project will understand the mechanisms underlying vaccine hypo-responsiveness across populations and find ways to reverse it. The project relies on the hypothesis that the variation in the immunological network due to exposure to microorganisms and parasites, and the cellular metabolism of populations residing in distinct environmental conditions, are responsible for vaccine hypo-responsiveness. Immunological and metabolic interventions can reverse it.
There is growing evidence that vaccine immunogenicity and efficacy present considerable variations across populations in high- and low/middle-income countries. For example, the vaccination of volunteers in Europe or USA with attentuated malaria vaccine can result in 100% protection, while efficacy drops to just 29% in Africa.
Similar trends are seen with other vaccines. The EU-funded REVERSE project will understand the mechanisms underlying vaccine hypo-responsiveness across populations and find ways to reverse it. The project relies on the hypothesis that the variation in the immunological network due to exposure to microorganisms and parasites, and the cellular metabolism of populations residing in distinct environmental conditions, are responsible for vaccine hypo-responsiveness. Immunological and metabolic interventions can reverse it.
1- A review article in Nature Reviews Immunology (PMID: 37770632) on immunological variation that might lead to variation in vaccine responses. This is an important part of REVERSE as it sets the scene in relation to published literature for the work that is being and will be carried out.
2- A paper in press in Lancet Microbe that compares the differences in immune profiles of people in Senegal and in the Netherlands and how they respond to SARS-CoV-2. These data will be linked to COVID vaccine responsiveness which will be studied within REVERSE.
3- Training of researchers from Uganda, Tanzania and Senegal, all doing their PhD. Through this training, we hope to create equity in our partnership that investigates vaccine hypo-responsiveness in countries like Uganda, Tanzania and Senegal.
4- Obtaining all ethical documents needed to perform the complex studies that involve vulnerable populations. Almost all DTAs and MTAs are in place, ensuring that REVERSE project abides to international codes of conduct.
5- Setting up of the tonsil organoid model using material not only from Europeans but also from Tanzania. In particular the ability to isolate and culture stromal cells that determine the tonsil microenvironment.
2- A paper in press in Lancet Microbe that compares the differences in immune profiles of people in Senegal and in the Netherlands and how they respond to SARS-CoV-2. These data will be linked to COVID vaccine responsiveness which will be studied within REVERSE.
3- Training of researchers from Uganda, Tanzania and Senegal, all doing their PhD. Through this training, we hope to create equity in our partnership that investigates vaccine hypo-responsiveness in countries like Uganda, Tanzania and Senegal.
4- Obtaining all ethical documents needed to perform the complex studies that involve vulnerable populations. Almost all DTAs and MTAs are in place, ensuring that REVERSE project abides to international codes of conduct.
5- Setting up of the tonsil organoid model using material not only from Europeans but also from Tanzania. In particular the ability to isolate and culture stromal cells that determine the tonsil microenvironment.
Creating a tight network of North-South-South collaboration, is the way forward for the understanding of the mechanisms behind variation in vaccine responses. Often such studies involve primarily sample collection in Global South and then analysis in Global North. We are proud of our partnership with Global South and their involvement in a project that we are all involved in and ensure that there is sufficient training of researchers from Global South for equity. Much is still needed to achieve a true equity in capabilities but REVERSE and support from ERC advanced is a real breakthrough to show that a high calibre funding agency shares the vision to work hand in hand with partners in Global South to achieve real innovation. This aspect was anticipated to form the backbone of the REVERSE project. The next two years will show how such collaborative efforts with the use of the technologies and pipelines developed in leading to breakthrough discoveries.