Determinants of early life immune responses to RSV infection

•Physical and immunological immaturity contribute to RSV disease in early life.•Infants exhibit distinct, not defective, responses to inflammatory stimuli.•Infant innate and adaptive immune responses demonstrate ineffective viral control.•Age-specific approaches will be necessary to generate effective immunity in infants.•Vaccination of pregnant mothers and young children may confer indirect protection.

Respiratory syncytial virus causes significant morbidity and mortality in both developed and developing countries, and a vaccine that adequately protects from severe disease remains an important unmet need. RSV disease has an inordinate impact on the very young, and the physical and immunological immaturity of early life complicates vaccine design. Defining and targeting the functional capacities of early life immune responses and controlling responses during primary antigen exposure with selected vaccine delivery approaches will be important for protecting infants by active immunization. Alternatively, vaccination of older children and pregnant mothers may ameliorate disease burden indirectly until infants reach about six months of age, when they can generate more effective anti-RSV immune responses.