Development, Current Status and Remaining Challenges for Respiratory Syncytial Virus Vaccines

Respiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children and the elderly. RSV vaccine development puzzled vaccinologists for years. Safety concerns of initial formulations, the lack of an absolute correlate of protection, as well as the need for selection of appropriate virus attenuation and antigen-adjuvant combination, contributed to delayed vaccine production. The recent stabilization of the RSV-F glycoprotein in the prefusion (preF) conformation that constitutes the primary target of RSV-neutralizing antibodies, was key for efficient vaccine design. Two protein subunit (GSK’s Arexvy and Pfizer’s Abrysvo) and one mRNA RSV vaccine (Moderna’s mRESVIA) are now available. RSV vaccines are approved for the prevention of RSV-lower respiratory tract disease (LRTD) in adults 60 years of age and older, with updated recommendations calling for the expansion of vaccination to all adults at increased risk for severe RSV disease. Abrysvo is the only vaccine indicated for use in pregnancy to prevent RSV-LRTD in infants from birth through 6 months of age. We provide a comparative assessment of the efficacy of approved RSV vaccines over a maximum of three seasons, summarizing currently available data. Despite the decreasing vaccine efficacy over time, which should be anticipated for a virus that is characterized by short-term immunity, efficacy was clinically meaningful over placebo. However, due to the recent vaccination approval, RSV vaccine efficacy data, particularly in specific subpopulations not represented in pivotal clinical trials, are lacking. Ongoing vaccine surveillance and further evaluation, particularly among immunocompromised patients, frail elderly subjects and young infants, is necessary. As in the success story of combined pediatric vaccines, combination vaccines, conferring protection against several respiratory illnesses in one dose, could help improve vaccine acceptance and coverage rates in older adults.