Immunity to respiratory syncytial virus: a clinical perspective

Abstract

Since its discovery 60 years ago, we have greatly improved our knowledge of RSV disease. Many risk factors for development of serious disease have been identified that include prematurity, pre-existing medical conditions, in utero influences, and old age. There is no therapy and treatment remains supportive with oxygen and fluid maintenance. The majority of infants hospitalized with RSV bronchiolitis were previously healthy. Understanding why these children develop severe RSV bronchiolitis, whereas others only have mild RSV infection, is the main object of this doctoral thesis. The greatest independent risk factor for developing serious disease is young age. Waning maternal antibodies and the ability of RSV to evade systemic immunity offers some explanation, but there is increasing evidence supporting immune mediated pathology to RSV. Approximately 20% of association with severe disease can be accounted to polymorphisms in genes regulating early immune responses. Interestingly, children with almost absent immunity, such as those undergoing stem cell transplantation, do not necessarily show progression to severe disease in case of RSV infection. The development of severe RSV bronchiolitis is associated with a more robust cascade of pro-inflammatory responses displayed by higher levels of nasopharyngeal cytokines such as IL-6. Furthermore, there is a unique pattern of increased local IL-17 production during the convalescent phase of bronchiolitis This observation suggests a critical role for the epithelium as the first line of defense against RSV and is in accordance with the hypothesis of immune mediated pathology. There is an association between the IL1RL1 gene and RSV disease severity. The newly found genetic link, in light of the well established link between IL1RL1 and asthma, makes it an interesting candidate for future research on association with disease severity and post-bronchiolitis complications. The cascade of immune responses may exert effects beyond RSV. Young infants clear colonizing pneumococci from the nasopharynx during the course of bronchiolitis. It is crucial to study the fluctuations in non-invasive bacterial colonization of the nasopharynx that occur during childhood in relation to viral infection and to recognize the complex dynamics of microbial communities in the upper respiratory tract, especially in the development and evaluation of candidate viral vaccines.