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.