The road to approved vaccines for respiratory syncytial virus

Abstract

After decades of work, several interventions to prevent severe respiratory syncytial virus (RSV) disease in high-risk infant and older adult populations have finally been approved. There were many setbacks along the road to victory. In this review, I will discuss the impact of RSV on human health and how structure-based vaccine design set the stage for numerous RSV countermeasures to advance through late phase clinical evaluation. While there are still many RSV countermeasures in preclinical and early-stage clinical trials, this review will focus on products yielding long-awaited efficacy results. Finally, I will discuss some challenges and next steps needed to declare a global victory against RSV.

Fig. 1. RSV countermeasures completing phase 3 testing in infants and older adults.

For protection of infants from RSV disease, the nirsevimab and clesrovimab half-life extended (YTE) mAbs are market-approved or nearing completion of phase 3 evaluation, respectively. The maternal RSVpreF bivalent subunit vaccine Abrysvo has been FDA approved for administration between 32 and 36 weeks of pregnancy, while development of the A subtype RSVPreF3 was stopped due to a safety signal. For protection of older adults, both the AS01_E-adjuvanted subtype A subunit Arexvy and unadjuvanted bivalent subunit Abrysvo have been approved by the FDA, while development of Ad26.RSV.preF-RSV preF and MVA-BN-RSV vaccines for older adults has been stopped. mRNA-1345 is nearing phase 3 completion. A thick green border indicates market approved, and thick red border indicates that product development and testing has been discontinued. Figure created using biorender.com.