The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates

Related People: Ruth A. Karron, MD
Related Research: RSV
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The global burden of disease caused by respiratory syncytial virus (RSV) is increasingly recognised, not only in infants, but also in older adults (aged ≥65 years). Advances in knowledge of the structural biology of the RSV surface fusion glycoprotein have revolutionised RSV vaccine development by providing a new target for preventive interventions. The RSV vaccine landscape has rapidly expanded to include 19 vaccine candidates and monoclonal antibodies (mAbs) in clinical trials, reflecting the urgency of reducing this global health problem and hence the prioritisation of RSV vaccine development. The candidates include mAbs and vaccines using four approaches: (1) particle-based, (2) live-attenuated or chimeric, (3) subunit, (4) vector-based. Late-phase RSV vaccine trial failures highlight gaps in knowledge regarding immunological protection and provide lessons for future development. In this Review, we highlight promising new approaches for RSV vaccine design and provide a comprehensive overview of RSV vaccine candidates and mAbs in clinical development to prevent one of the most common and severe infectious diseases in young children and older adults worldwide.

Acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV) has gained recognition as a global health problem with a high burden of disease, and no vaccine licensed for prevention.In children under 5 years, it is estimated that 33∙1 million episodes of ALRI, 3∙2 million hospital admissions, and as many as 118 200 deaths were attributable to RSV worldwide in 2015 (figure 1).1 Although often characterised as a paediatric disease, RSV infection in adults represents a substantial health burden.

Development of effective RSV vaccines and monoclonal antibodies (mAbs) presents both opportunities and challenges. First, concerns of enhanced respiratory disease (ERD) following vaccination with the formalininactivated RSV (FI-RSV) vaccine in the 1960s have complicated the design and testing of RSV vaccines.9 Second, an absolute correlate of protection against a clinically relevant RSV infection remains elusive, although cell-mediated immunity,10 mucosal IgA,11 and potent neutralising antibodies12 have been associated with decreased disease severity.