First RSV vaccine approvals

The world's first vaccines for respiratory syncytial virus (RSV) have been approved in the USA and Europe. RSV causes a major burden of respiratory disease worldwide and can lead to serious and sometimes fatal respiratory tract infections and bronchiolitis, particularly in older people (aged ≥65 years), young children (<5 years), and individuals with underlying chronic diseases such as pulmonary disease and circulatory conditions. Globally, 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range 25·4–44·6 million) and 101 400 RSV-attributable overall deaths (84 500–125 200) occurred in young children in 2019. Previous efforts to develop an RSV vaccine have faced several challenges, including the rapidly changing structure of the F protein on the viral surface. Attempts to formulate a vaccine in the 1960s were unsuccessful; a formalin-inactivated vaccine caused severe lung inflammatory responses during natural RSV infection in children, leading to two infant deaths. Alternative RSV vaccine development was therefore hindered for many decades over safety concerns. However, advances in understanding of the virus’ biology and structure have led to multiple trials and recent publication of encouraging results. On May 3, 2023, the US Food and Drug Administration (FDA) approved the world's first RSV vaccine, Arexvy, for individuals aged 60 years and older. Arexvy was also approved by the European Union on June 7, 2023. A second RSV vaccine, Abrysvo, was approved by the FDA on May 31, 2023, also for individuals aged 60 years and older. Additionally, on May 18, 2023, an FDA panel of advisers voted that data supported the efficacy and safety of a candidate maternal RSV vaccine, given to pregnant women to protect infants aged up to 6 months. The approval of Arexvy was based on an international, randomised, phase 3 trial of adults aged 60 years and older. 12 467 participants were assigned one dose of the RSV prefusion F protein-based vaccine, and 12 499 were assigned one dose of placebo. After a median follow-up of 6·7 months, vaccine efficacy against RSV-related lower respiratory tract disease (the trial primary objective) was 82·6% (96·95% CI 57·9–94·1). Abrysvo, another RSV prefusion F protein-based vaccine, was approved on the basis of a large, randomised, phase 3 trial of adults aged 60 years and older. At an interim analysis, 17 215 participants had received the vaccine, and 17 069 the placebo. Vaccine efficacy against RSV-associated lower respiratory tract illness with at least two signs or symptoms was 66·7% (96·66% CI 28·8–85·8). Vaccine efficacy against severe RSV illness, defined by at least three symptoms, was 85·7% (96·66% CI 32·0–98·7). The maternal vaccine, assessed in an international, phase 3, randomised trial of pregnant women at 24–36 weeks’ gestation, was given to 3682 participants, with 3676 receiving placebo. Vaccine efficacy against the primary endpoint of medically attended severe RSV-associated lower respiratory tract illness occurring within 90 days after birth was 81·8% (99·5% CI 40·6–96·3). John Tregoning (Imperial College London, London, UK) commented “It is an extraordinarily exciting time for RSV vaccines. Research has been ongoing for nearly 60 years without success until recently and we now look like having vaccines that work in the two most important age groups—the very old and the very young. Where deployed, these will have a huge impact by reducing the burden of infection, particularly on paediatric units in the winter months.” Andrew Shorr (Medstar Washington Hospital Center, Washington DC, USA) added “The approval of a new vaccine for RSV in adults, along with multiple clinical trials documenting the safety and efficacy of several different RSV vaccine platforms, therefore is welcome news. Also exciting are recent data demonstrating how the vaccination of pregnant women against RSV can provide protection for their infants.” Neither trial of older adults demonstrated that the RSV vaccines prevented hospitalisations; however, Shorr highlighted that this “likely reflects the low general rate of hospitalisation in the participants studied.” Louis Bont (Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands) commented “We need better data on the incidence of severe infection leading to hospitalisation in the general home-dwelling population.” Additionally, regarding the maternal RSV vaccine, some of the FDA panel members raised concerns about a possible associated risk of preterm birth. Shorr commented “I think the issues of preterm birth are worthy of close attention as the vaccine is rolled out into clinics.” As more RSV vaccines and preventive interventions become available, an important consideration will be to find ways to increase their accessibility in low-resource countries. Most mortality from respiratory diseases occur in low-income or middle-income countries, including more than 97% of RSV-attributable deaths in children. Shorr commented: “Multiple analyses indicate that RSV vaccination can prove cost-effective both in high and low-income nations, provided there are effective means for distribution to those most in need.” Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysisRSV contributes substantially to morbidity and mortality burden globally in children aged 0–60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0–60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. Full-Text PDF Open Access