Passive Immunoprophylaxis against Respiratory Syncytial Virus in Children: Where Are We Now?

Abstract

Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab’s usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio.

Epidemiology and prevention of respiratory syncytial virus infections in children in Italy

“…The development of vaccines or mAbs against RSV has been included among the priorities of the World Health Organization (WHO) [ 32 ]. To date, 38 candidates comprising vaccines and mAbs are in clinical trials; several are expected to be available within the next 5 years [ 18 , 33 ].…”

“…To contribute to a significant reduction in the burden of infections and hospitalizations, future vaccines and mAbs against RSV must provide protection that is more extended over time and available for use in all neonates and infants [ 19 , 33 , 47 ].…”

“…The new approaches currently being tested include maternal vaccines for pregnant women to protect neonates during the first months after birth through transplacental transfer of maternal antibodies; mAbs to provide immediate protection for up to 5 months after administration, for use in all neonates and infants during the first months of life; and pediatric vaccines that could be administered to infants a few months after birth to provide immunity lasting for years [ 19 , 33 , 47 ].…”

“…The main approaches currently being investigated and developed are summarized in Table 4 [ 5 , 6 , 17 – 19 , 32 , 33 , 47 ].…”

A novel effective live-attenuated human metapneumovirus vaccine candidate produced in the serum-free suspension DuckCelt®-T17 cell platform

“…Despite this important clinical burden, there is currently no licensed vaccine or specific antiviral against human pneumoviruses. To date, only one humanized monoclonal antibody (Palivizumab) was regulatory approved for the passive immunoprophylaxis against severe HRSV infection in high-risk infants and children 6,7 .…”