Elucidating helminth-mediated suppression of anti-influenza vaccination efficacy using Systems Vaccinology

• Applicants: Professorin Dr. Marylyn Martina Addo, since 12/2023; Professorin Dr. Minka Breloer
• Subject Area: Immunology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 499035099

Vaccinations are the most successful prophylactic interventions against life-threatening infectious diseases. However, extrinsic factors, like pre-existing helminth infections, can dampen the immune response and thereby impair vaccine efficacy. Recently, Systems Vaccinology approaches have been developed to gain a deeper insight into vaccine-induced immune responses and mechanisms leading to vaccine efficacy or failure. This approach combines multiple omics technologies to collect data on e.g. transcriptomic changes, microRNA dynamics and changes of immune cells and signalling molecules at multiple time points and in multiple organs before and after vaccination. These data are then combined in a computational approach in order to understand the mechanisms of protective immunity and to identify markers of early innate immune responses that may predict the outcome of vaccination. The AG Emerging Infections established Systems Vaccinology in the framework of first-in-human studies and successfully identified predictors of high antibody titres following vaccination by using the Ebola virus vaccine candidate VSV-EBOV. Using a murine model for human filariasis the AG Helminth Immunology demonstrated that infection with L. sigmodontis reduced the influenza-specific antibody (Ab) response to vaccination. This was associated with higher viral burden and increased pathology compared to naive vaccinated mice in a challenge infection with the human pathogenic 2009 pandemic H1N1 Influenza A virus (swine flu). Strikingly, the suppressed phenotype was observed in mice with either acute, chronic, or already cleared helminth infection, indicating that helminth infection has a sustained impact on the immune system of its host. The aim of the proposed study is to better understand, how helminth infections influence vaccine-induced responses and vaccine efficacy. Combining the expertise of the AG Emerging Infections and AG Helminth Immunology, we aim to apply the unbiased approach of Systems Vaccinology to the well-established mouse model of helminth-induced suppression of vaccine responses. Immune response against anti-influenza vaccination will be analyzed in helminth-infected and previously helminth-infected mice compared to naive mice. Using bioinformatics and integrative approaches data will be correlated with vaccine-induced protection in an influenza challenge infection model. We hypothesize that acutely helminth-infected mice and mice with a history of a resolved helminth infection share a signature that correlates with reduced vaccine response. In the long run, our aim is to identify markers that predict vaccine response in the context of a helminth infection. A broader knowledge of mechanisms underlying vaccine efficacy and failure might contribute in future vaccine development strategies to reduce vaccine failure in the context of co-morbidities.

• DFG Programme: Research Grants
• Ehemalige Antragstellerin: Dr. Christine Dahlke, until 12/2023