Translational sciences approach to RSV vaccine development

Abstract

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and the elderly. Despite its relatively low degree of antigenic variation, it causes frequent reinfection throughout life. Clinical manifestations of RSV disease and the immune response to infection differ in infants and the elderly, suggesting that vaccines designed to protect these two populations may require different attributes. Here, the authors describe the translational approach of utilizing data from epidemiology studies performed in these populations, the use of RSV diagnostics in clinical practice, lessons learned from previous vaccine clinical trials and the success of palivizumab in prevention of RSV disease in premature and high-risk infants to aid the development of safe and effective RSV vaccines.

Keywords::

• elderly
• live-attenuated vaccine
• neutralizing antibody
• palivizumab
• respiratory syncytial virus
• RSV diagnostic
• subunit vaccine
• T cell
• tetramer

Financial & competing interests disclosure

R Tang, MS Galinski, K Wang, F Zuo, A Cherukuri, RA Gasser Jr., E Malkin, F Sifakis, DB Mendel and MT Esser were all employees of MedImmune inc. at the time the manuscript was written. V Kurzweil was a summer intern at MedImmune from the University of Pennyslvania at the time the manuscript was written. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Respiratory syncytial virus (RSV) is the leading cause of hospitalization and lower respiratory illnesses in children under age 5 and causes significant morbidity and mortality in the elderly.

• • High levels of RSV-specific serum IgG and RSV-specific nasal wash IgA correlate with reduced RSV infection and disease in infants and adults.

• • Reduced T cell numbers or function correlates with increased severity of RSV disease in both the young and the elderly.

• • Newer, more sensitive, multiplex respiratory virus PCR diagnostics are being more widely utilized and have demonstrated that RSV causes a significant amount of respiratory illness in the elderly and high-risk populations.

• • Both live-attenuated vaccines and subunit vaccines are currently being evaluated in Phase I and II clinical trials and the next 5 years will prove to be an exciting time in RSV vaccine development as the results of these clinical trials become available and several other vaccine candidates enter clinical trials.

Notes