Review Article How might infant and paediatric immune responses influence malaria vaccine efficacy?

Naturally acquired immunity to malaria requires repeat infec-tions yet does not engender sterile immunity or long-lasting protective immunologic memory. This renders infants and young children the most susceptible to malaria-induced mor-bidity and mortality, and the ultimate target for a malaria vaccine. The prevailing paradigm is that infants initially gar-ner protection due to transplacentally transferred anti-malar-ial antibodies and other intrinsic factors such as foetal haemoglobin. As these wane infants have an insufficient immune repertoire to prevent genetically diverse Plasmodium infections and an inability to control malaria-induced immu-nopathology. This Review discusses humoral, cell-mediated and innate immune responses to malaria and how each con-tributes to protection – focusing on how deficiencies in infant and paediatric immune responses might influence malaria vac-cine efficacy in this population. In addition, burgeoning evi-dence suggests a role for inhibitory receptors that limit immunopathology and guide the development of long-lived immunity. Precisely how age or malaria infections influence the function of these regulators is unknown. Therefore the possibility that infants may not have the immune-dexterity to balance effective parasite clearance with timely immune-regulation leading to protective immunologic memory is con-sidered. And thus, malaria vaccines tested in adults and older children may not be predictive for trials conducted in infants