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.

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

All circulating immunoglobulin G (IgG) antibodies in human newborns are of maternal origin1 and transferred across the placenta to provide passive immunity until newborn IgG production takes over 15 weeks after birth2. However, maternal IgG can also negatively interfere with newborn vaccine responses3. The concentration of IgG increases sharply during the third trimester of gestation and children delivered extremely preterm are believed to largely lack this passive immunity1,2,4. Antibodies to individual viruses have been reported5–12, but the global repertoire of maternal IgG, its variation in children, and the epitopes targeted are poorly understood. Here, we assess antibodies against 93,904 epitopes from 206 viruses in 32 preterm and 46 term mother–child dyads. We find that extremely preterm children receive comparable repertoires of IgG as term children, albeit at lower absolute concentrations and consequent shorter half-life. Neutralization of the clinically important respiratory syncytial virus (RS-virus) was also comparable until three months of age. These findings have implications for understanding infectious disease susceptibility, vaccine development, and vaccine scheduling in newborn children. A longitudinal survey of maternal antiviral antibodies in newborns provides a blueprint for understanding infectious disease susceptibility and vaccine development, and inform vaccine scheduling in newborn children.

/pdf/the-repertoire-of-maternal-anti-viral-antibodies-in-human-155gn484id.pdf

The repertoire of maternal anti-viral antibodies in human newborns

Rationale: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is believed to result from uncontrolled viral replication, an exces...

/pdf/reduced-nasal-viral-load-and-ifn-responses-in-infants-with-481mfrixsf.pdf

Reduced Nasal Viral Load and IFN Responses in Infants with Respiratory Syncytial Virus Bronchiolitis and Respiratory Failure.

Respiratory syncytial virus (RSV) is the most common single cause of respiratory hospitalisation of infants and is the second largest cause of lower respiratory infection mortality worldwide. In adults, RSV is an under-recognised cause of deterioration in health, particularly in frail elderly persons. Infection rates typically rise in late autumn and early winter causing bronchiolitis in infants, common colds in adults and insidious respiratory illness in the elderly. Virus detection methods optimised for use in children have low detection rate in adults, highlighting the need for better diagnostic tests. There are many vaccines under development, mostly based on the surface glycoprotein F which exists in two conformations (prefusion and postfusion). Much of the neutralising antibody appears to be to the prefusion form. Vaccines being developed include live attenuated, subunit, particle based and live vectored agents. Different vaccine strategies may be appropriate for different target populations: at-risk infants, school-age children, adult caregivers and the elderly. Antiviral drugs are in clinical trial and may find a place in disease management. RSV disease is one of the major remaining common tractable challenges in infectious diseases and the era of vaccines and antivirals for RSV is on the near horizon.

https://thorax.bmj.com/content/thoraxjnl/74/10/986.full.pdf

Respiratory syncytial virus (RSV): a scourge from infancy to old age.

Assessing the strength of evidence for a causal effect of respiratory syncytial virus lower respiratory tract infections on subsequent wheezing illness: a systematic review and meta-analysis.

http://diposit.ub.edu/dspace/bitstream/2445/116939/1/scheltema2017_2695.pdf

Hsin Chi

Papers

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series