Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape.
Mazur NI., Terstappen J., Baral R., Bardají A., Beutels P., Buchholz UJ., Cohen C., Crowe JE., Cutland CL., Eckert L., Feikin D., Fitzpatrick T., Fong Y., Graham BS., Heikkinen T., Higgins D., Hirve S., Klugman KP., Kragten-Tabatabaie L., Lemey P., Libster R., Löwensteyn Y., Mejias A., Munoz FM., Munywoki PK., Mwananyanda L., Nair H., Nunes MC., Ramilo O., Richmond P., Ruckwardt TJ., Sande C., Srikantiah P., Thacker N., Waldstein KA., Weinberger D., Wildenbeest J., Wiseman D., Zar HJ., Zambon M., Bont L.
Respiratory syncytial virus is the second most common cause of infant mortality and a major cause of morbidity and mortality in older adults (aged >60 years). Efforts to develop a respiratory syncytial virus vaccine or immunoprophylaxis remain highly active. 33 respiratory syncytial virus prevention candidates are in clinical development using six different approaches: recombinant vector, subunit, particle-based, live attenuated, chimeric, and nucleic acid vaccines; and monoclonal antibodies. Nine candidates are in phase 3 clinical trials. Understanding the epitopes targeted by highly neutralising antibodies has resulted in a shift from empirical to rational and structure-based vaccine and monoclonal antibody design. An extended half-life monoclonal antibody for all infants is likely to be within 1 year of regulatory approval (from August, 2022) for high-income countries. Live-attenuated vaccines are in development for older infants (aged >6 months). Subunit vaccines are in late-stage trials for pregnant women to protect infants, whereas vector, subunit, and nucleic acid approaches are being developed for older adults. Urgent next steps include ensuring access and affordability of a respiratory syncytial virus vaccine globally. This review gives an overview of respiratory syncytial virus vaccines and monoclonal antibodies in clinical development highlighting different target populations, antigens, and trial results.