Development Attempts to develop an RSV vaccine began in the 1960s with an unsuccessful
inactivated vaccine developed by exposing the RSV virus to
formalin (formalin-inactivated RSV (FI-RSV)). This early vaccine induced
vaccine-associated enhanced respiratory disease (VAERD), in which children who had not previously been exposed to RSV and were vaccinated would develop severe RSV disease if exposed to the virus itself, including
fever,
wheezing, and
bronchopneumonia. A 2019 paper similarly claimed that research toward developing a vaccine had advanced greatly over the prior 10 years, with more than 30 candidates in some stage of development. The same study predicted that a vaccine would be available within ten years. A 2013 study detailed the crystal structure of the
RSV fusion (F) protein and how its stability could be improved. This provided the basis for finding the most effective F protein constructs, which are used in RSV vaccines. In February 2023, results of a phase III study of around 25,000 participants age 60+ were published. One dose of the Arexvy vaccine provided 94% efficacy against severe RSV pneumonia and 72% efficacy against RSV acute respiratory infection. An advisory panel to the FDA recommended approval of the vaccine in February 2023. In April 2023, the
Committee for Medicinal Products for Human Use of the
European Medicines Agency (EMA) recommended to grant a marketing authorization for Arexvy for the prevention of RSV lower respiratory tract disease in people 60 years of age or older after review under the EMA's accelerated assessment program. In May 2023, the FDA's expert panel unanimously recommended Abrysvo for approval in pregnant women. The panel was split on the safety of the vaccine in respect of preterm births. In June 2023, Arexvy was authorized for medical use in the European Union. The
mRNA vaccine Mresvia was approved for medical use in the United States in May 2024. which showed that immune responses were non-inferior in people aged 50–59 years of age at increased risk for RSV disease compared to people aged 60 years of age and older. Mresvia was authorized for medical use in the European Union in August 2024. , other vaccines were in development, including vaccines for pregnant women to immunize their fetuses by passing maternal antibodies to them, and vaccines for children. The vaccine's antigen is a stabilized version of the RSV F protein, which was developed using structure-based vaccine design. This trial was terminated in February 2022, on the advice of an external Data Monitoring Committee, because of an excess of premature births in the trial arm. The FDA analyzed data from an ongoing, randomized, placebo-controlled clinical study conducted in the US and internationally in individuals 60 years of age and older. In April 2023, Pfizer published their interim results of their phase III study of a RSV vaccine for adults age 60 and older in over 34,000 participants. One dose of the vaccine was 67% efficacious in preventing infections with at least two symptoms and it was 86% effective against more severe disease, in people with three related symptoms. The vaccine's protection was consistent across different subgroups, and was 62% effective in preventing acute respiratory illness caused by RSV infection. In April 2023, Pfizer published interim results of their double blind phase III study in about 3,600 pregnant women, with another 3,600 women receiving a placebo. One dose of the vaccine provided 81% efficacy in preventing severe infection within three months after birth and 69% in six months after birth. The most common side effects were pain at the injection site, headache, muscle pain and nausea. It was approved for medical use in the United States in May 2024. It protects against lower respiratory tract disease caused by RSV in adults aged 60 years and older. It is also used in adults aged 18 to 59 years who are at increased risk for lower respiratory tract disease caused by RSV. During studies, this vaccine is under the name of mRNA-1345 vaccine. It is a vaccine that uses messenger RNA technology. It is a lipid nanoparticle that contain mRNA which encodes the RSV F-protein stabilized in the prefusion conformation.
Phase 2/3 trial The phase 2/3 trial of 2024 evaluated the humoral immunogenicity of the mRNA-1345 vaccine in adults older than 60 years old. A total of approximatively 35,000 participants were randomized, and an immunogenicity subset (mRNA-1345: n=1515; placebo: n=333) was analysed. Results showed that at 29 days after vaccination, mRNA-1345 induced strong increases in neutralizing antibodies (nAbs) against both RSV-A and RSV-B, with 8.4-fold and 5.1-fold rises, respectively, compared with baseline. Seroresponse rates (≥4-fold increase) were 74.2% for RSV-A and 56.5% for RSV-B, greatly exceeding placebo responses. Binding antibodies (bAbs) to the preF antigen also increased, showing a 7.7-fold increase after vaccination. mRNA-1345 vaccine enhanced an antibody response across all demographic and risk groups. Overall, mRNA-1345 vaccine produced robust and rapid humoral immune responses across diverse high-risk populations. So, it provides protection against RSV in older persons who are predisposed to severe disease. Given natural infection with RSV does not confer lifelong protection, revaccination may be required after primary vaccination. The need and timing for revaccination with RSV vaccines is being evaluated in studies.
Revaccination trial This study evaluated if revaccination with the mRNA-1345 vaccine after 12 months is safe and immunogenic in adults older than 50 years old. In this phase 3 trial, there were 543 participants and it included 525 patients that were included in the immunogenicity analyses. Those participants received 50 μg booster dose of mRNA-1345 12 months later. Revaccination was safe and well tolerated, with mostly mild, short-lasting local and systemic reactions and no vaccine-related serious adverse events. At Day 29, neutralizing antibody responses to RSV-A and RSV-B met noninferiority criteria compared with the primary dose, with geometric mean titer ratios of 1.08 and 0.91, respectively. Antibody levels increased substantially after revaccination and remained above baseline through 12 months. Seroresponse rates were 77.5% for RSV-A and 47.5% for RSV-B. Immunogenicity was consistent across demographic subgroups. Overall, mRNA-1345 revaccination was safe and well tolerated. The immunogenic response was comparable to the primary dose ad it was effective across all subgroups. So, these findings support the potential use of annual revaccination for adults ≥50 years, especially those at higher risk for severe RSV. == Society and culture ==