(Vienna, 24 May 2017), Simone Schüller from the Department of Pediatrics and Adolescent Medicine at MedUni Vienna/Vienna General Hospital is being recognised as Early Career Investigator in the August edition of leading paediatric journal "Pediatric Research".
Simone Schüller is lead author of the study "Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro", which will appear in print in August.
The characterisation of age-related molecular responses to licensed vaccines as precursor to the development of age-specific vaccines
Vaccinations against pathogenic germs are an important step in the fight against the high global morbidity and mortality figures for babies and young children. However, because they are immunologically immature, this vulnerable patient group often fails to respond sufficiently to vaccination, so that adequate protection cannot always be achieved, especially in premature babies (preterm infants). A promising approach in prevention of preventable infections is to use effective adjuvants to enhance the action of vaccines for this age group.
Scientific findings from the last few years show that vaccines, with and without vaccine enhancers, work differently in different age groups. This particularly affects newborns, and especially preterm infants, but also older people with declining immunity.
The aim of this study is to increase our understanding about how vaccinations work with different vaccine adjuvants on an immunological-cellular level. By determining so-called secretomes, that is to say the totality of those proteins released by stimulated antigen-presenting cells in vitro, it is hoped to discover more about the signalling pathway of these cells.
In a suitable in-vitro model, monocytes, potent antigen-presenting cells, are first of all isolated from the umbilical cord blood or the blood of adults. These neonatal (premature and newborn) and adult (healthy adults, aged over 65) monocytes are then incubated with one of the licensed vaccines commonly used throughout the world: Bacille Calmette-Guérin (BCG), a TB vaccine, Hepatitis B Virus (HBV), pneumococcal PCV13, acellular (aP) and cellular (wP) pertussis (whooping cough). The messenger substances excreted by the monocytes in response (secretomes) are then analysed using mass spectroscopy. The results are graphically represented in the form of a "heatmap" and, in a further step, selected proteins are verified using another tried and tested method for detecting antibodies (ELISA). Following statistical analysis, conclusions can be drawn about the signalling pathway of these cells, resulting in a new insight into (1) adjuvants and (2) age-related immune responses.
Preliminary results that have already been published show an age-related difference on the level of secretomes and signal transduction following cellular stimulation with aluminium hydroxide, a vaccine enhancer that has been used for years throughout the world, compared with so-called Toll-like Receptor Agonists (TLR-A), a new generation of adjuvants.
It is hoped that this study will provide new insights into the age-related mode of action of vaccines with and without enhancers, in order to identify new biomarkers and develop better, age-specific vaccinations. Improved vaccinations could help to provide better protection from potentially life-threatening infections, especially for the youngest (premature and newborn babies) and oldest (65+) among us.
About Simone Schüller
Simone Schüller studied medicine at the Medical University of Vienna and went on to do her postdoctoral qualification at the Department of Nephrology at the University Hospital in Bern and at the Department of Pediatrics and Adolescent Medicine of MedUni Vienna/Vienna General Hospital (Division of Neonatalogy, Intensive Care Medicine and Neuropediatrics). She completed her specialist training in paediatrics and adolescent medicine in 2015. Currently (since May 2017) she is working in a postdoc post at Boston Children's Hospital (USA). The focus of her research is immunology in newborn and preterm infants.
Service: Pediatric Research
Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro – Schüller SS, Wisgrill L, Herndl E, Spittler A, Förster-Waldl E, Sadeghi K, Kramer BW, Berger A. Pediatr Res. 2017 Mar 13. doi: 10.1038/pr.2017.41.
Further relevant studies
S. Schüller, L. Wisgrill, K. Sadeghi, E. Gindl, H. Helmer, P. Husslein, A. Berger, A. Spittler, E. Förster-Waldl: The TLR-specific Adjuvants R-848 and CpG-B Endorse the Immunological Reaction of Neonatal Antigen Presenting Cells, Pediatr Res. 2016 Apr 8. doi: 10.1038/pr.2016.71.
S. Schüller, K. Sadeghi, S. Diesner, A. Prusa, K. Klebermasz, H. Helmer, P. Husslein, A. Pollak, A. Spittler, E. Förster-Waldl: Preterm Neonates Display Altered Plasmocytoid Dendritic Cell Function and Morphology, J Leukoc Biol. 2013 Feb 11