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Trinity researchers are working to make childhood vaccination even more effective

To coincide with World Immunisation Week, we spoke to School of Medicine researchers who are working on paediatric immunisations.

Vaccinations have saved millions of lives, but still millions of children die before the age of two every year of infectious diseases. This raises the question of whether childhood vaccination could be made even more effective. In their first year, children receive vaccinations against dangerous infections, but achieve protection only after several booster vaccinations. This is because elements of their immune systems are not fully ‘mature’ and do not function in the same way as an adult’s immune system. This leaves a so called ‘window of vulnerability’ in a child’s life before booster vaccinations can be administered and take effect. To maximise the effectiveness of vaccines, adjuvants can be added to boost the immune response. Researchers in the TCD’s School of Medicine aim to narrow this window of vulnerability in a child’s life by identifying and developing innovative adjuvants for paediatric vaccines, improving paediatric responses to vaccines.

Activating a strong response in cells of the innate immune system is a key strategy for inducing long-lasting vaccine responses as this arm of the immune system kickstarts the adaptive immune response to make T cells and B cells capable of fighting specific infections. Because of this, activators of the innate immune system are attractive targets for the development of adjuvants. Unfortunately, many innate immune signalling pathways are impaired in new-born children. Evidence suggests that elements of the innate immune system, currently being targeted for vaccine adjuvanticity do not fully develop until puberty and it is likely that effective adjuvants for the neonatal and paediatric populations are being overlooked due to modelling of responses in adult systems. Professor Sarah Doyle, Associate Professor of Immunology, School of Medicine explains:

Our research has identified a family of cytosolic nucleic acid (CNA) sensors, including RIG-I, whose function is remarkably intact in neonatal cells, in contrast to other innate immune pathways. These receptors activate pathways important for vaccine responses and these responses remain intact throughout childhood and adolescence.”

The groups work has been published in several important journals, including the Journal of Immunology, Cytokine, and more recently, the Journal of Leukocyte Biology. Their work has found that combining multiple immune activators, or adjuvants, may be key to activating different parts of the neonatal immune response and improving response to vaccines. Describing the work, Dr Kiva Brennan, Research Fellow in the Trinity College Institute of Neuroscience, said:

By improving activation of the neonatal immune system, we hope that in the future we could improve paediatric responses to a range of vaccines and allow for earlier vaccination or improved protection from an earlier age.”

The team collaborate with Professor Fionnuala McAuliffe, National Maternity Hospital, Professor Eleanor Molloy, School of Medicine, Dr Sri Paran, Children’s Health Ireland (CHI) at Crumlin, and Professor Ed Lavelle, School of Biochemistry and Immunology. Engagement with parents of young children is also paramount. The team have imminent plans to survey expectant parents and parents of young children, with a view to understanding parent’s experience of the current vaccine schedule and determine whether reduced numbers of injections in the primary vaccination schedule, while maintaining the current level of protection, is of interest to them. Dr Brennan emphasises the importance of the patients’ contribution:

We are very grateful to the parents & children who gave blood both in Holles St. and CHI Crumlin, without which this work would not be possible.”

The research, which was funded by The National Children’s Research Centre, Health Research Board and Science Foundation Ireland has been presented at the Keystone ‘Innovative Vaccine Approaches’ conference in 2021 and won an award at the TCD Health Sciences Research blitz in 2021. Dr Doyle describes the work’s impact:

“Our ongoing work could add an innovative paediatric-specific vaccine adjuvant to the development pipeline for paediatric vaccines. It has the potential to improve vaccine responses so fewer boosters are needed, narrowing the window of vulnerability to vaccine-preventable infection in a child’s life.”

For more on World immunisation Week, visit: https://www.who.int/campaigns/world-immunization-week

To read the team’s recently-published peer-reviewed paper in the Journal of Leukocyte Biology, see here: https://doi.org/10.1002/jlb.5a0521-242r