RFPs: Understanding How Infections Foster and Induce Non-Communicable Diseases

Scope

• Infectious agent (IA) and non-communicable disease (NCD) interplay has driven effective prevention strategies. However, a growing field of research suggests that there are many unexplored connections between IAs and NCDs that could be utilised to develop better diagnostic, preventative, and therapeutic approaches to burdensome diseases. A cohort analysis identified 96 distinct NCDs correlated to IAs. Other cohort analyses identified neurodegenerative diseases, defined as the progressive loss of neurons resulting in loss of motor function or cognition, with links to viral infection, including Alzheimer’s disease, amyotrophic lateral sclerosis, dementia, vascular dementia, Parkinson’s disease and multiple sclerosis. IA links to cardio-metabolic NCDs such as HSV (Herpes simplex viruses) and coronary artery disease, CMV (cytomegalovirus), EBV (Epstein-Barr virus), VZV (varicella-zoster virus), influenza and parvovirus B19 have been shown to induce cardiomyopathies, and H. pylori infections may drive myocardial infarction.
• While cancer, autoimmune, neurological, and cardiometabolic NCDs all have significant links to IAs, the scope of this topic is focused on neurodegenerative and cardiometabolic diseases, which carry significant disease burdens, potentially caused by direct, immune-mediated, or microbiota-gut-brain-axis damage/dysregulation, and lack early intervention strategies. Via the action funded under this topic, Europe’s research community could potentially find more infection-based approaches for diagnosing, preventing, and treating NCDs.
• The action funded under this topic aims to identify potential causal links and biomarkers leading to mechanism of action (MoA) studies. The literature demonstrates research cohorts’ utility in exploring the interplay between IAs and NCDs, increasing the likelihood of success. For instance, causative links were determined for oncolytic viruses, EBV and human papillomavirus (HPV), using Hill’s causation criteria. The action funded under this topic should:
  • develop methodologies to demonstrate non-carcinogenic IA to NCD causal relationships;
  • consolidate data in one repository of IA/NCD causal relationships, biomarkers, and MoA
• Applicants are expected to define a strategy to assess non-carcinogenic infection-associated NCD causative links and related biomarkers, incorporating a modelling perspective alongside AI-assisted data mining, appropriate statistical methodologies, and prioritisation approaches for the exploration of mechanisms of action (MoA). Applicants should also detail their methodological approach and data collection procedures, providing preliminary data to show potential for success and strategies for mitigating main methodological risks and limitations.
  • As part of the first objective of proposed activities, applicants should work toward generating robust evidence toward proof of causality rather than only strengthening the known associations of IAs and NCDs. Applicants should take advantage of the available research cohorts, biobanks, and exposome data, including microbiota-gut-brain-axis samples from large general population studies, neurodegenerative disease cohorts, or cardiovascular disease cohorts. Association strength, consistency, and specificity should be indicated by similarity of measurement across different cohorts. Insurance data could be used to analyse temporality where infection occurs prior to medically attended disease. Cohorts from patients that have received transplants or immunosuppressive treatments with longitudinal data could demonstrate temporality and biological gradient effects from opportunistic infections, the strength of the immune response to IAs to demonstrate elements of causality driven by immune-mediated damage. Selection of research cohorts should prioritise data sets with populations from diverse ethnicities, socio-economic statuses, and balanced for gender. Applicants should develop/use pre-clinical models for causal link plausibility verification. Applicants are expected to follow and comply with all relevant ethical and data privacy standards for research. Applicants are also expected to conduct their consortium work with full transparency, clearly communicating data provenance, model interpretability, traceability, and limitations, especially when using AI modelling and decision-making.
  • The second objective is identifying novel biomarkers, ideally to classify associated IAs, to better stratify individuals (children, adults, the elderly) who are at risk of developing NCDs post infection. This could be done using immune or metabolic markers, host and microbiome metabolomics, sequencing, etc. This pillar can utilise the same cohorts, biobanks, and exposome data used for pillar 1 if sufficient, but should supplement with additional cohorts where needed. To ensure outcomes within the 5-year timeframe of the project, the launch of new prospective cohorts is out of scope but limited recruitment to fill specific data gaps in existing cohorts could be considered.
  • The third objective is to define the MoA that IAs use to drive NCD development. MoA identification would require tissue samples from pillars 1 & 2, as well as pre-clinical or in silico experimentation according to the targeted conditions or diseases.

Funding Information

• Budget (EUR) – Year 2025: 37 209 000
• Contributions: around 7127000

Expected Outcomes

• The action under this topic must contribute to all of the following outcomes:
  • Accelerated access to interventions: A better understanding of the potential causal links between infections and non-communicable diseases and their accompanying biomarkers could:
    • more precisely define a person’s level of risk for long term health complications
    • lead to the development of better diagnostic approaches such as early detection and monitoring strategies that will make preventive medicine more effective for the benefit of patients.
  • Development of vaccine strategies: A better understanding of the potential causal links between infections and chronic diseases could lead to the generation of vaccine strategies with the capacity to prevent the development of one or more chronic diseases over the course of a person’s life, significantly reducing the long-term burden of disease.
  • Early intervention strategies: A clear understanding of the mechanisms of action used by infections to cause chronic diseases could more precisely define which cellular processes, metabolic pathways, enzymatic activities, and gene expression changes should be the focus of early intervention strategies. These strategies could halt or potentially reverse the progression of chronic diseases and would aim to replace many current treatments that only manage symptoms.
  • Improved quality of life: A better understanding of the potential causal links between infections and chronic diseases, as well as the biomarkers and mechanisms of action involved, could more precisely define development strategies for prophylactic vaccines, early diagnosis, and early intervention therapeutics that could significantly improve the quality of life of individuals by preventing health decline and avoiding escalating healthcare costs.
  • Adoption of innovative approaches: The establishment of a more systematic collaborative approach to mining existing research cohorts and biobanks to determine potentially causal links between infections and chronic diseases by combining multi-omics, artificial intelligence, and pre-clinical model verification to potentially accelerate the development of prophylactic vaccine, early diagnostic and early intervention strategies.

Eligibility Criteria

• Entities eligible to participate:
  • Any legal entity, regardless of its place of establishment, including legal entities from nonassociated third countries or international organisations (including international European research organisations) is eligible to participate (whether it is eligible for funding or not), provided that the conditions laid down in the Horizon Europe Regulation have been met, along with any other conditions laid down in the specific call/topic.
  • A ‘legal entity’ means any natural or legal person created and recognised as such under national law, EU law or international law, which has legal personality and which may, acting in its own name, exercise rights and be subject to obligations, or an entity without legal personality.
• To become a beneficiary, legal entities must be eligible for funding.
• To be eligible for funding, applicants must be established in one of the following countries:
  • the Member States of the European Union, including their outermost regions:
    • Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden.
  • the Overseas Countries and Territories (OCTs) linked to the Member States:
    • Aruba (NL), Bonaire (NL), Curação (NL), French Polynesia (FR), French Southern and Antarctic Territories (FR), Greenland (DK), New Caledonia (FR), Saba (NL), Saint Barthélemy (FR), Sint Eustatius (NL), Sint Maarten (NL), St. Pierre and Miquelon (FR), Wallis and Futuna Islands (FR).
  • countries associated to Horizon Europe;
    • Albania, Armenia, Bosnia and Herzegovina, Canada, Faroe Islands, Georgia, Iceland, Israel, Kosovo, Moldova, Montenegro, New Zealand, North Macedonia, Norway, Serbia, Tunisia, Türkiye, Ukraine, United Kingdom.

For more information, visit EC.