Introduction
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in infants and of pneumonia in children younger than 5 years of age in infants [1,2], and in this population it is responsible each year for approximately 33 million cases of lower respiratory tract infections (LRTI) worldwide [1]. It is recognized to cause substantial mortality in low and middle-income countries [2], and burden in high-income countries [3,4]; the highest rate of hospitalization is in infants aged less than 3 months [5]. Despite this, preventive measures are to date limited to the monthly injection of RSV-specific neutralizing antibodies for children at a high risk of severe complications, the cost of which may be prohibitive [6]. There are, however, vaccines currently in development that have the potential to be a more affordable option to reduce the worldwide RSV burden [6]. Most candidate vaccines target the fusion protein, which is an envelope protein highly conserved between different subtypes or RSV, stabilized in its prefusion form [7,8]. However, RSV nucleoprotein (N protein), which it is implicated in nucleocapsid-RNA complex formation that allows RSV replication and transcription [9], is one of the most conserved viral protein among strains [10] and is also considered as a potential target for candidate vaccines inducing T CD8+ response [11,12]. These vaccines may be good candidates for maternal immunization strategy; an approach that appears as safe because of the particular vulnerability of infants and their inability to produce effective antibodies [13]. Such a strategy has already demonstrated its ability to provide a passive humoral protection for infants against tetanus, influenza, and pertussis [14]. Humoral protection is conferred at birth by the transfer of maternal IgG, the titer of which depends on the maternal level of RSV antibodies and the effectiveness of transplacental RSV antibody transfer from mother to infant [15]. Although the protection conferred to infants by neutralizing antibodies induced by natural exposure to RSV of mothers has been suggested, published data is conflicting [16–20]; furthermore there is no published data concerning the protection provided by maternal antibodies against the N protein. The aim of the present study was therefore to investigate the association between maternal antibody titers against the RSV N protein at birth and the newborns’ risk of developing RSV VS-LRTI early in infancy.