Respiratory syncytial virus vaccine

A respiratory syncytial virus vaccine, or RSV vaccine, is a vaccine that protects against respiratory syncytial virus. RSV affects an estimated 64 million people and causes 160,000 deaths worldwide each year.

The RSV vaccines Arexvy (GSK), Abrysvo (Pfizer), and Mresvia (Moderna) are approved for medical use in the United States. Arexvy is approved for medical use in the United States, in the European Union, and in Canada for adults aged 60 years of age and older. Arexy is approved in the US for adults aged 50-59 years of age who are at increased risk. In June 2024, the US Centers for Disease Control and Prevention (CDC) updated its recommendation for the use of respiratory syncytial virus vaccine in people aged 60 years of age and older. The CDC recommends that people who have not received the respiratory syncytial virus vaccine and are aged 75 years of age and older receive the respiratory syncytial virus vaccine; and that people who have not received the respiratory syncytial virus vaccine and are aged 60–74 years of age who are at increased risk of severe respiratory syncytial virus, meaning they have certain chronic medical conditions, such as lung or heart disease, or they live in nursing homes, receive the respiratory syncytial virus vaccine.

Research to develop an RSV vaccine continued for decades; a 2013 study led to the approved vaccines. Work on RSV vaccines also supported the rapid development of COVID-19 vaccines.

Medical uses
Respiratory syncytial virus vaccine is indicated for active immunization for the prevention of lower respiratory tract disease caused by respiratory syncytial virus in people 60 years of age and older.

Abrysvo is also indicated for immunization of pregnant individuals at 32 through 36 weeks gestational age for the prevention of lower respiratory tract disease caused by respiratory syncytial virus in infants from birth through six months of age. Abrysvo is approved for use in pregnant women at 24 through 36 weeks and older adults in the European Union. and between 28 through 36 weeks and older adults in the UK.

Infant-specific issues include the immature infant immune system and the presence of maternal antibodies, which make infantile immunization difficult.

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 vaccine induced vaccine-associated enhanced respiratory disease, in which children who had not previously been exposed to RSV and were subsequently vaccinated would develop severe RSV disease if exposed to the virus itself, including fever, wheezing, and bronchopneumonia. Some eighty percent of such children (vs. 5% of virus-exposed controls) were hospitalized, and two children died of lethal lung inflammation during the first natural RSV infection after vaccination of RSV-naive infants. This disaster slowed vaccine development for many years.

A 1998 paper reported that research had advanced greatly over the previous 10 years. 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. Candidates included particle-based vaccines, attenuated vaccines, mRNA vaccines, protein subunit vaccines, and vector-based vaccines. 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. To develop its vaccine, Pfizer engineered 400 different F protein constructs to identify the most immunogenic, and constructed a bivalent RSV prefusion F investigational vaccine.

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 adults 60 years of age or older after review under EMA's accelerated assessment program.

In May 2023, Arexvy was approved for adults aged 60 and older, making it the first FDA-approved RSV vaccine.

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 approved for medical use in the European Union.

In May 2024, the mRNA vaccine Mresvia was approved for medical use in the United States.

In June 2024, the FDA approved Arexvy for use in adults aged 50 to 59 who are at an increased risk of RSV-caused lower respiratory tract disease (LRTD). The approval is based on data from a phase III study (NCT05590403), which showed that immune responses were non-inferior in adults aged 50-59 at increased risk for RSV disease compared to adults aged 60 and older.

Clinical trials
, Phase III trials by multiple companies are ongoing to test RSV vaccines for adults aged 60 years of age and above. These include vaccines by GSK, Pfizer, Johnson & Johnson, Moderna, and Bavarian Nordic. , other vaccines were in development, including vaccines for pregnant women to immunize their fetuses by passing maternal antibodies to them, and vaccines for children.

GSK
In November 2020, GSK's vaccine, GSK3888550A, entered Phase III trials for pregnant women. 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. The main clinical study was designed to assess the safety and effectiveness of a single dose administered to individuals 60 years of age and older. Participants agreed to remain in the study through three RSV seasons to assess the duration of effectiveness and the safety and effectiveness of repeat vaccination. Data from the first RSV season of the study were available for the FDA's analysis. In this study, approximately 12,500 participants received vaccine and 12,500 participants received a placebo. The vaccine reduced the risk of developing RSV-associated lower respiratory tract disease (LRTD) by 82.6% and reduced the risk of developing severe RSV-associated LRTD by 94.1%. The FDA granted the application priority review designation and granted approval of Arexvy to GlaxoSmithKline Biologicals.

In October 2022, GSK started a Phase III, observer-blind, randomized, placebo-controlled study to evaluate the safety of the vaccine in adults 50-59 years of age compared to adults 60 years of age and older. The vaccine elicited an immune response in adults aged 50 to 59 at increased risk for RSV disease due to select underlying medical conditions that was non-inferior to that observed in adults aged 60 and above, meeting the trial’s primary co-endpoint.

Pfizer
RSVpreF (Abrysvo) is a bivalent recombinant protein subunit vaccine which consists of equal amounts of stabilized prefusion F antigens from the two major RSV subgroups: RSV A and RSV B.

In April 2023, Pfizer published their interim results of their Phase III study of a RSV vaccine for adults age 60 and above 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.

In a subgroup of pregnant individuals who were 32 through 36 weeks gestational age, of whom about 1,500 received Abrysvo and 1,500 received placebo, Abrysvo reduced the risk of lower respiratory tract disease by 34.7%, and reduced the risk of severe lower respiratory tract disease by 91.1% within 90 days after birth when compared to placebo. Within 180 days after birth, Abrysvo reduced the risk of lower respiratory tract disease by 57.3% and by 76.5% for severe lower respiratory tract disease, when compared to placebo. In a second study, about 100 pregnant individuals received Abrysvo and approximately 100 pregnant women received placebo.

Moderna
Mresvia is an mRNA vaccine that was studied in clincal trial NCT05127434. It was approved for medical use in the United States in May 2024.

Legal status
In June 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Mresvia, intended for the prevention of lower respiratory tract disease caused by respiratory syncytial virus. The applicant for this medicinal product is Moderna Biotech Spain S.L.