Studies to understand the response of the infant’s immune system to infectious diseases and vaccines

Despite progress overall in reducing the number of children dying before they reach the age of five, deaths in the first year of life and even more strikingly in the first month of life have not fallen in the same way. At this age many babies die as the result of infections.
The research being carried out in the infant immunology group aims to reduce deaths from infection in this most vulnerable group though better understanding the way the immune (or defence) system works.
We want to understand the best possible ways to give some of the vaccine we already have available. This might include giving vaccine to mums so that the immunity they generate (the antibodies) can protect a baby as soon as the baby is born (before the baby can be vaccinated themselves). We also want to know how the baby’s immune system responds when it comes across an infection. If understood this better we might be able to improve these response, for example with new vaccines, so the baby would not become unwell. Finally we carry out research which gives us a better understanding of how vaccines themselves working in babies. This research includes new vaccines against malaria, HIV and TB as well as established vaccines like the pneumococcal vaccine. Understanding better the vaccines we have should allow the next generation of vaccines to be designed even more effectively so that less newborns and infants die needlessly.

Millennium Development Goal 4 sets out to reduce mortality in children under five-years of age. Despite progress with this overall, including in many countries across sub-Saharan Africa, mortality in infancy and in particular in newborns has so far been comparatively resistant to intervention. Although the reasons for this are multi-factorial, many deaths in this period occur as a result of infections. Consequently, understanding the distinct way in which infants respond to infections and vaccines, facilitating the rational development of novel interventions to protect newborns is a top global health priority. These areas are the focus of current research within infant immunology.
Objectives:
To characterise the key elements of the immune response to given pathogens (e.g. pneumococcus, staphylococcus) which may be associated with the development of natural immunity to these agents in order to facilitate the develop novel protective strategies
To describe, at both a cellular and a humoral level, the immunity generated by currently licensed (e.g. rotavirus) as well as experimental (e.g. malaria, HIV, TB) vaccines in order to guide future rational vaccine development
To establish the optimum regimens for the use of current vaccines (e.g. inactivated poliovirus vaccine, pneumococcal conjugate vaccines) which will maximise the protection of infants while also ensuring the logistical challenges of vaccine delivery on a large scale (e.g. through using fractional doses, novel delivery methods, maternal immunisation, multi-dose vials) are met
Methodology:
These critical objectives are being addressed across a series of maternal and infant cohorts.
A combination of interventional studies, including GCP-clinical vaccine trials, as well as longitudinal observational studies, is used according to the questions being addressed. We have the established capacity to recruit mothers antenatally allowing newborns to be followed right from delivery. We also recruit infants over the first year of life as they are presented for their routine immunisations
A range of laboratory approaches are used including large-scale serological studies monitoring correlates of vaccine induced protection, as well detailed immunological investigations. Such studies, which are often nested within larger scale trials, use techniques including multi-parameter flow-cytometry, ELISpot assays, evaluation of cytokines and antibodies using Luminex-based multi-analyte technology.
Impact
The findings of certain key studies (e.g. inactivated poliovirus vaccine trial) are expected to directly influence WHO policy over the coming year. Other work is focussed on studying pathogens (e.g. pneumococcus, malaria, rotavirus) which remain at the top of the research agenda internationally and address question recognised to be high priority.