Understanding immunological maturation in early life
Acute respiratory infections including the pneumococcal disease, pertussis and Respiratory Syncytial Virus (RSV), are very severe before the age of six months. The only preventive measure against them is vaccination very early in life at an age of relative immunological immaturity. However, knowledge of the immunological factors that during early infancy may result in a high susceptibility to these infections and may be related to the vaccine-induced response is still limited. Addressing these needs, the NEOVAC project focused on the analysis of human early life Dendritic Cells (DC) defects. These immunocompetent cells are found in lymphoid and haemopoietic systems as well as the skin and present or process antigens and hence stimulate cellular immunity. The studies involved the functional characterisation of human DC in early life, the potential of novel adjuvant/delivery systems to enhance DC activation and T cell responses to vaccine antigens. More specifically, researchers specified myeloid DC defects in newborns that may be relevant to the deficiencies of immune responses. Exposure to microbial products such as the bacterial lipopolysaccharide or Bordetella pertussis toxin was shown to be a major factor for immune immaturation of neonatal DC. In addition, these in contrast to adult DCs, produce less interleukin-12 that is released in response to infection and promotes the activation of cell-mediated immunity, i.e. stimulation of T cells. A decreased transcription of the gene encoding the p35 chain of the cytokine was found responsible for this defect. With the aid of recombinant interferon-gamma, neonatal DC may become able to produce bioactive interleukin-12. However, there are still great differences between neonatal mice and human cell models, but all data derived is useful for the identification of DC defects. Thereby, this data may significantly contribute to the development of new immunisation strategies in the neonatal period.
