RSV-Naïve Infants Pose a Challenge to RSV Vaccine Development

The hunt is on for a vaccine against deadly respiratory syncytial virus (RSV), but a poor understanding of the molecular mechanisms of infection and acquired immunity have slowed vaccine research and development.

Respiratory syncytial virus (RSV) is an enveloped RNA virus that targets the surface airway epithelial cells, frequently provoking bronchoconstriction and wheeze.1 It is the leading cause of viral acute lower respiratory infections, severe respiratory infections, and associated morbidity and deaths among infants around the world for which no vaccine is yet available; more than 30 million pediatric RSV infections are believed to occur globally each year.1 By age 2 years, nearly all children have experienced at least one RSV infection—most by age 6 months.1,2 Each year, approximately 150,000 children younger than age 2 years are hospitalized with RSV infections in the U.S. alone.2,3 Up to 40 per 100 of these infants will exhibit symptoms of bronchiolitis or pneumonia and up to 20 per 1000 will be hospitalized.2

Elderly and immunocompromised adults are also affected.1,2,4 RSV is responsible for an estimated 177,000 hospitalizations and 14,000 deaths among elderly Americans, each year.5

Among infants, preterm birth is a risk factor for severe RSV and complications.2,3 While most severe infections involve infants who were born at-term, preterm infants face higher RSV risks even when they do not have chronic lung or congenital heart disease.3 Authors of a 2016 systematic review of 85 published studies concluded that in western nations, RSV infection-associated hospitalization risk tends to be higher among preterm infants (born at gestational age <37 weeks) than among healthy born-at-term babies.3

RSV hospitalization rates (RSVH) “ranged from ~5 per 1000 children to >100 per 1000 children with the highest rates shown in the lowest gestational-age infants” with a high strength of evidence, the authors reported.3 “Independent risk factors associated with RSVH include: proximity of birth to the RSV season, living with school-age siblings, smoking of mother during pregnancy or infant exposure to environmental smoking, reduced breast feeding, male sex, and familial atopy (asthma) […]”. 

Preterm infants might face higher risks because of their smaller lung volumes and airway surface areas, and lower levels of immune antibodies than at-term infants.3 In western nations, severe RSV and associated morbidity is a “major burden” on healthcare systems, particularly among preterm infants during the winter RSV season.3

While palivizumab prophylaxis is available for infants at highest risk for severe  RSV infection, there remains an urgent need for an effective vaccine against these infections. However, the molecular mechanisms and correlates of acquired RSV immunity are poorly understood; this has slowed efforts to develop an RSV vaccine.1