Ricerc@Sapienza

RRSV infection manifests with a wide clinical spectrum ranging from asymptomatic to severe respiratory illness. Thus, understanding the factors predisposing to severe RSV infection are goals of outstanding importance.
A recent review estimated that, in 2015, RSV caused 33.1 million episodes of acute LRI in children younger than 5 years worldwide. Virtually all subjects has been infected by RSV by the age of 2 years, and RSV has shown to cause frequent reinfections during life with a wide range of symptoms, while the age dependent impairment in the immune response together with the limited reserve of the lung make this virus to privilege the subjects during infancy and during old age. However, it is not known which are the viral/ host determinants that influence the severity of respiratory diseases in a fraction of infected, previously healthy infants, determining the need for hospitalization. Bronchiolitis can be considered an intense inflammation of the lower airways associated to severe disease in some infants and to respiratory sequelae later in life. Moreover, despite almost of the subjects are infected by the virus in the first year of life, RSV reinfection is a significant cause of asthma exacerbations in childhood and of chronic obstructive pulmonary disease exacerbations in the adult/old population. The host immune response in healthy subjects is usually able to fight the infection and limit the airway inflammation but it is not currently known why in some subjects it fails in the response and sometimes worsen the disease.
Discrepancies among published studies on the extent and role of anti-RSV immune response in infants may be due to a different anti-RSV immune status at birth, i.e. exposed or not during pregnancy. That maternal exposure to RSV can lead to the virus reaching the fetus was established in mice models and by only one study in humans (7). The hypothesis underlying this project is that prenatal exposure to RSV may induce an RSV-specific immune response in the fetus that can confer protection to postnatal RSV severe disease in infants. The identification of RSV infected mothers will permit to compare cytokine responses among not exposed and exposed children. The detection of RSV in cord blood may discriminate children prenatally infected or not-infected.
Our first element of innovation is, therefore, the ultimate goal of our project: to demonstrate that prenatal exposure to RSV can confer protection to postnatal RSV severe disease in the first year/years of life. The second important element of innovation is that with our project we are shedding light on the mother-to-child crosstalk during pregnancy. The demonstration that a first RSV contact can happen during prenatal life and that this may confer a protective immunity in postnatal life would change the way of approach RSV diseases by making more feasible the prevention with the ongoing anti-RSV maternal vaccine (already in phase III clinical trials). The third outcome is the initial enrollment of a birth cohort that will be prospectively followed through their first winter for development of RSV infection and then for the subsequent six years for acute respiratory symptoms by telephone interviews to evaluate recurrent wheezing risk. In a similar way, the pediatricians are currently following a cohort of term, non-low birth weight, healthy infants hospitalized with bronchiolitis at the Paediatric Department, ¿Sapienza¿ University of Rome (named BROME [Bronchiolitis in Rome]).
A fourth achievement will come from the parallel study on CMV primary infection, conducted on residual biological samples from mother/newborn pairs.
The feasibility of this project is based on ad hoc multidisciplinary approach among virologists, infectivologist and pediatricians, and the external unit of gynecology/obstetrician and statisticians. Virologists, pediatricians and statisticians have been collaborating since a long time, as witnessed by numerous research papers. Our consolidated research team will be enriched by the specific expertise of gynecologists, allowing the exploration of innovative issues in view of a promising maternal vaccination approach. Expected results may also catalyze the development of new strong collaborations of this research group with the Asthma and Airway Disease Research Center, University of Arizona, aiming at developing synergistic outcomes and opening future prospective in scientific projects (i.e. submission of a research grant proposal to NIH).
Results of the study will be presented to national (Italian Pediatric Respiratory society, SIMRI) and international (American thoracic Society, ATS and European Respiratory Society, ERS) congresses and then they will be published in international journals.