Respiratory Syncytial Virus, an Ongoing Medical Dilemma

An Expert Commentary on Respiratory Syncytial Virus Prophylactic and Therapeutic Pharmaceuticals Currently in Clinical Trials

Lindsay Broadbent; Helen Groves; Michael D. Shields; Ultan F. Power

Disclosures

Influenza Resp Viruses. 2015;9(4):169-178. 

In This Article

Abstract and Introduction

Abstract

As the most important viral cause of severe respiratory disease in infants and increasing recognition as important in the elderly and immunocompromised, respiratory syncytial virus (RSV) is responsible for a massive health burden worldwide. Prophylactic antibodies were successfully developed against RSV. However, their use is restricted to a small group of infants considered at high risk of severe RSV disease. There is still no specific therapeutics or vaccines to combat RSV. As such, it remains a major unmet medical need for most individuals. The World Health Organisations International Clinical Trials Registry Platform (WHO ICTRP) and PubMed were used to identify and review all RSV vaccine, prophylactic and therapeutic candidates currently in clinical trials. This review presents an expert commentary on all RSV-specific prophylactic and therapeutic candidates that have entered clinical trials since 2008.

Introduction

Discovered in 1956, respiratory syncytial virus (RSV) was quickly identified as the leading cause of lower respiratory tract infections (LRTI) in infants worldwide.[1] Respiratory syncytial virus is a member of the Paramyxoviridae family, Pneumovirus genus. With a 15·2-kB single-stranded negative sense RNA genome, RSV contains 10 genes encoding 11 proteins, including the fusion (F) and attachment (G) surface glycoproteins, which constitute the principle target antigens for RSV vaccines. Two RSV subgroups exist (A and B), distinguished primarily by genetic and antigenic differences in the G gene and protein. Respiratory syncytial virus virions have two reported forms: spherical particles (≤300 nm diameter) and long filamentous forms (2–10 μm).[2,3] Respiratory syncytial virus is responsible for up to 33·8 million LRTI cases yearly, approximately 3·4 million hospitalisations and up to 199 000 deaths worldwide, predominantly in developing countries.[4,5] For example, Kenya reported RSV-related LRTI rates of 7100/100 000 in children <5 years[6] versus 1042/100 000 in England.[7] Furthermore, in many countries, RSV is comparable to influenza regarding mortality rates and health and economic burdens in children.[8]

Symptoms such as rhinorrhea, coryza, sore throat and malaise are features of mild RSV infection.[9] Clinical signs of RSV-LRTI include dyspnoea, cyanosis, subcostal recession, low-grade fever, wheezing and consolidation.[10,11] RSV-LRTI is responsible for 85% of bronchiolitis and 20% of pneumonia in infants.[12] In the first year of life, 1–3% of infants are hospitalised with severe RSV-LRTI. Mechanical ventilation is required in 10% of hospitalised infants, of which 5–10% succumb to RSV infection.

Risk factors associated with the development of severe RSV-LRTI include the following: prematurity; bronchopulmonary dysplasia; congenital lung or heart conditions; male gender; age ≤6 months; neuromuscular disorders; and immunodeficiency. Trisomy 21 and cystic fibrosis were also recently identified as possible risk factors.[13]

There are no effective vaccines or specific drugs against RSV. Treatment has remained largely unchanged since the 1960s and is mainly supportive. A number of Cochrane reviews have noted short-term clinical benefit in the use of nebulised adrenaline.[14] However, meta-analyses on hypertonic saline, bronchodilator and glucocorticoid use have not shown clinical benefit,[15,16] and currently, only supportive management is recommended.

Recently, there has been a tremendous increase in interest and investment within the pharmaceutical sector in vaccine and drug development against RSV. Several exciting developments are being pursued and optimism is high that effective RSV drugs and vaccines are achievable.

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