Determinants of early life immune responses to RSV infection

Abstract

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.

Vaccine development for respiratory syncytial virus

“…First, the primary virus infection targets young infants who have immunological features like immature dendritic cell function and lack of B cell somatic hypermutation that inherently limit magnitude and repertoire of responses [27–29]. In addition, the NS1 and NS2 proteins which assume the dominant position in the gene order, have many mechanisms for inhibiting Type I IFN [30], and the shed portion of the G glycoprotein can alter dendritic cell signaling [31] and serve as a decoy for antibody responses [32].…”

Respiratory syncytial virus infection: an innate perspective

“…Thus, it is possible that the development of severe disease is due to an early lack of control of the virus, which leads to epithelial cell damage and a high release of pro-inflammatory mediators that recruit and activate leukocytes in the lung and induce an excessive immune response that results in immunopathology 20, 24– 26 . The risk groups for severe RSV disease are the young (less than one year of age) and the old (more than 65 years of age) 27, 28 . Infants have an immature immune system, which renders them less able to mount an efficient anti-viral response 28, 29 .…”

“…The risk groups for severe RSV disease are the young (less than one year of age) and the old (more than 65 years of age) 27, 28 . Infants have an immature immune system, which renders them less able to mount an efficient anti-viral response 28, 29 . In addition, it is likely that structural features including small airway calibre may make infants more prone to critical airway narrowing and resultant hypoxia in the face of lung inflammation 28 .…”

“…Infants have an immature immune system, which renders them less able to mount an efficient anti-viral response 28, 29 . In addition, it is likely that structural features including small airway calibre may make infants more prone to critical airway narrowing and resultant hypoxia in the face of lung inflammation 28 . The elderly have a senescing immune system and are therefore less able to induce appropriate responses to invading pathogens 30, 31 .…”

Immunometabolism and innate immunity in the context of immunological maturation and respiratory pathogens in young children

“…Generally, low levels of IFNγ production from epigenetically regulated immune cells persist throughout early childhood as compared with older children or adults . Despite limitations imposed by immunological immaturity, innate cells in the young child still exhibit the capacity to respond to pathogens, suppress, or eliminate an invading pathogen as viral loads during respiratory viral infections can be comparable with adults, and can stimulate the development of adaptive immune cells albeit less efficiently . However, the effect of limited innate immunity in the developing child as it correlates to the high level of morbidity commonly observed in this population during viral infection and compensatory changes in cell types, numbers, or functions or as it relates to dysfunction in their ability to fully prime T cells (which are prone to apoptosis in the lungs during viral infection) is not well known.…”