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Respiratory syncytial virus infection and novel interventions

Nature Reviews Microbiology volume 21, pages 734–749 (2023)Cite this article

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Abstract

The large global burden of respiratory syncytial virus (RSV) respiratory tract infections in young children and older adults has gained increased recognition in recent years. Recent discoveries regarding the neutralization-specific viral epitopes of the pre-fusion RSV glycoprotein have led to a shift from empirical to structure-based design of RSV therapeutics, and controlled human infection model studies have provided early-stage proof of concept for novel RSV monoclonal antibodies, vaccines and antiviral drugs. The world’s first vaccines and first monoclonal antibody to prevent RSV among older adults and all infants, respectively, have recently been approved. Large-scale introduction of RSV prophylactics emphasizes the need for active surveillance to understand the global impact of these interventions over time and to timely identify viral mutants that are able to escape novel prophylactics. In this Review, we provide an overview of RSV interventions in clinical development, highlighting global disease burden, seasonality, pathogenesis, and host and viral factors related to RSV immunity.

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Fig. 1: Global disease burden of respiratory syncytial virus.
Fig. 2: The respiratory syncytial virus virion and replication cycle.
Fig. 3: Crystal structures of the respiratory syncytial virus fusion protein in pre-fusion and post-fusion state and its neutralizing epitopes.
Fig. 4: Factors associated with respiratory syncytial virus disease severity in infants.
Fig. 5: Combined antiviral and immunomodulatory therapy for the treatment of respiratory syncytial virus infections.
Fig. 6: Preventive and therapeutic pipeline for the treatment of respiratory syncytial virus infections.

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Acknowledgements

The authors thank C. Gill for his extensive feedback on the manuscript and M. van Wijk for her excellent assistance in data collection. The authors thank J. Terstappen, K. Chappin and J. Willemsen for their creative input in figure design.

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  1. Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, Utrecht, the Netherlands

    Annefleur C. Langedijk & Louis J. Bont

  2. ReSViNET Foundation, Zeist, the Netherlands

    Louis J. Bont

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  1. Annefleur C. Langedijk
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L.J.B. has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. University Medical Centre Utrecht (UMCU) has received major funding (>€100,000 per industrial partner) for investigator-initiated studies from AbbVie, MedImmune, AstraZeneca, Sanofi, Janssen, Pfizer, MSD and MeMed Diagnostics. UMCU has received major funding for the RSV GOLD study from the Bill and Melinda Gates Foundation. UMCU has received major funding as part of the public–private partnership Innovative Medicines Initiative (IMI)-funded RESCEU and PROMISE projects with partners GSK, Novavax, Janssen, AstraZeneca, Pfizer and Sanofi. UMCU has received major funding from Julius Clinical for participating in clinical studies sponsored by MedImmune and Pfizer. UMCU received minor funding (€1,000–25,000 per industrial partner) for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, GSK, Novavax, Pfizer, Moderna, AstraZeneca, MSD, Sanofi and Janssen. L.J.B. is the founding chairman of the ReSViNET Foundation. Since April 1, 2021, L.J.B. has been given a new position as medical scientific division manager of the Children’s Division of the Wilhelmina Children’s Hospital in Utrecht. A.C.L. has no conflict of interest to disclose.

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Nature Reviews Microbiology thanks Richard Hegele; David Marchant; and Ultan Power, who co-reviewed with Courtney Hawthorn; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Langedijk, A.C., Bont, L.J. Respiratory syncytial virus infection and novel interventions. Nat Rev Microbiol 21, 734–749 (2023). https://doi.org/10.1038/s41579-023-00919-w

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