2015

2015. this study provides novel insights into the basic immune response to RSV contamination in an important and understudied risk populace, providing prospects for future studies that are essential for the prevention and treatment of severe RSV disease in older adults. IMPORTANCE Respiratory syncytial computer virus (RSV) can cause severe morbidity and mortality Cinchocaine in certain risk groups, especially infants and older adults. Cinchocaine Currently no (prophylactic) treatment is usually available, except for a partially effective yet highly expensive monoclonal antibody. RSV therefore remains a major public health concern. To allow targeted development of novel vaccines and therapeutics, it is of great importance to understand the immunological mechanisms that underlie (protection from) severe disease in specific risk populations. Since most RSV-related studies focus on infants, there are only very limited data available concerning the response to RSV in the elderly population. Therefore, in this study, RSV-induced antibody responses and local cytokine secretion were assessed in community-dwelling older adults. These data provide novel insights that will benefit ongoing efforts to design safe and effective prevention and treatment strategies for RSV in an understudied risk group. KEYWORDS: elderly, interferon, cytokine, mucosa, IgG, IgA INTRODUCTION Although primarily known for causing severe disease in infants, respiratory syncytial computer virus (RSV) is progressively recognized to cause severe morbidity and mortality in older adults (1,C3). Globally, RSV acute respiratory infections in older adults were estimated to have resulted in 336,000 hospitalizations in 2015, causing an estimated 14,000 in-hospital deaths and likely many more outside the hospital setting (3). Other than a partially effective and very expensive monoclonal antibody (palivizumab), which is used only in high-risk infants (4), there are currently no vaccines or specific antivirals available for the prevention and treatment of RSV disease. The development of safe and effective strategies critically depends on a thorough understanding of the immunological mechanisms underlying (protection from) severe disease. However, these mechanisms and associated correlates of protection may not be the same in different risk groups. For example, unlike infants, older adults have already experienced multiple RSV infections throughout life and often suffer from waning immunity. Although there is a vast amount of literature available on the human immune response to RSV contamination (for a review, see research 5), most studies focus on the infant populace, and only a few statement data around the immune response in older adults (6,C10). While most RSV vaccination strategies that are currently being developed aim at inducing virus-specific antibodies, the extent to which these contribute to protection and their exact protective mechanisms remain uncertain (for a review, see research 11). RSV particles contain two major surface glycoproteins: the attachment protein (G) and the fusion protein (F). In particular, antibodies targeting the prefusion form of the F protein (pre-F) appear to mediate neutralization (12), although G-specific antibodies are also likely to contribute (13). However, the neutralizing capacity of RSV-specific serum immunoglobulin G (IgG) appears not to correlate well with protection (8, 14). Higher titers might show a better chance of being guarded, but a protective threshold probably does not exist (8, 14). The concentration of RSV-specific IgA in the nasal mucosa appears to correlate slightly better Cinchocaine with protection than serum IgG level, but this response is usually short-lived, and again, an established protective threshold is lacking (8, 14, 15). Notably, most studies investigating the antibody response to RSV have focused on infants or nonelderly adults. RSV primarily infects the epithelia of the upper and lower respiratory tract. Whereas the majority of individuals experience only moderate symptoms upon contamination, infants and elderly persons can develop severe, life-threatening disease, such as bronchiolitis and pneumonia. The mechanisms underlying severe RSV disease are incompletely comprehended, but a dysregulated immune responsefor example, due to an immature or waning immune responseappears to be an important component (for a review, see research 16). Notably, the production of cytokines in the respiratory mucosa is likely of crucial importance in modulating the subsequent immune response (for a review, see research 17). Again, whereas many studies provide data on mucosal cytokine expression in infants, data specific to ANGPT2 the older adult populace are scarce (9). In this study, antibody and local cytokine responses were assessed in RSV-infected older adults (60?years of age) during acute contamination and recovery. RSV-specific neutralization titers and IgG concentrations were decided in serum, as well as antigen-specific IgA and cytokine concentrations in nasal samples..