Project Details
Projekt
Influenza during pregnancy: The emergence of highly virulent H1N1 influenza virus strains and consequences for maternal and offspring’s health
Applicants
Professorin Dr. Petra Clara Arck; Professorin Dr. Gülsah Gabriel; Professor Dr. Hans-Willi Mittrücker
Subject Area
Gynaecology and Obstetrics
Term
from 2015 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 255154572
Compared to the general population, pregnant women are more likely to suffer from severe and even fatal influenza. During the 2009 H1N1 influenza pandemic, high morbidity and mortality rates were repeatedly observed among pregnant women. We have previously established an influenza virus infection model in pregnant mice, which reproduces the clinical features observed in pregnant women with severe courses of disease. Insights arising from this mouse model obtained during the first funding period of the KFO296 revealed that the anti-viral immune response in the pregnant mouse was significantly restricted as compared to the non-pregnant host. This included a reduced type I interferon response as well as impaired migration of CD8+ T cells into the lung. The multi-faceted failure to mount an anti-viral response in allogenic pregnant mice resulted in a less stringent selective environment that promoted the emergence of 2009 H1N1 virus variants that specifically counteract type I interferon response and mediate increased viral pathogenicity. Thus, in continuation of this project, we now seek to pursue a translational approach, in which we will characterise influenza virus isolates from pregnant women for the presence of innate immune escape variants with increased pathogenicity. Interestingly, our application of the steroid hormone progesterone in order to mirror a pregnancy-like endocrine milieu in non-pregnant mice, revealed an increased mortality, suggesting that progesterone is involved in dampening the host’s immune response against pandemic H1N1 virus. Thus, another focus will be to understand how progesterone may affect the anti-viral innate and adaptive immune response. Moreover, we will analyse maternal microchimerism as a potential factor to modulate offspring’s health towards influenza virus infections in the long-term. In summary, our project will elucidate underlying mechanisms that mediate severe influenza in pregnant women and potentially affect offspring’s immune response. Results obtained from this proposal will underscore the importance of the currently poor vaccination compliance in pregnant women and might further open novel therapeutic avenues.
DFG Programme
Clinical Research Units
