Respiratory syncytial virus vaccine

Respiratory syncytial virus vaccine
A respiratory syncytial virus vaccine, or RSV vaccine, is a vaccine which protects against infection by respiratory syncytial virus. The RSV vaccines Arexvy (GSK), and Abrysvo (Pfizer), were approved for medical use in the United States in May 2023. Arexvy was approved for medical use in the European Union in June 2023 and was approved in August 2023 for use in Canada for adults aged 60 or older.
Research to develop an RSV vaccine has been ongoing for decades; a study published in 2013 led to approved vaccines. The work on RSV vaccines also paved the way for fast development of COVID-19 vaccines.
In August 2023, the US Food and Drug Administration (FDA) approved Abrysvo for use in pregnant individuals to prevent lower respiratory tract disease and severe lower respiratory tract disease caused by respiratory syncytial virus in infants from birth through six months of age. In August 2023, the European Commission approved Abrysvo for use with both babies up to six months of age and older adults in the European Union.
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.
Since September 2023, it is also indicated in the continental United States as seasonal protection during September through end of January for pregnant women as a one-time dose at 32 to 36 weeks gestation to prevent RSV-infection in infants younger than 6 months.
History
Development
Research to develop an RSV vaccine has been ongoing for decades, with a study published in 2013 that lead to the approved vaccines. The work on RSV vaccines also paved the way for fast development of the COVID-19 vaccines.
There has been interest and research in RSV vaccine discovery, given the virus's disease burden and the lack of disease-specific therapies; RSV affects an estimated 64 million people and causes 160,000 deaths worldwide each year. However, vaccine development has faced significant obstacles that have blocked its progress. Among these are infant-specific factors, such as the immature infant immune system and the presence of maternal antibodies, which make infantile immunization difficult. The desired vaccine would prevent lower respiratory infection from RSV in at-risk populations and if possible, be useful in other populations with less risk.
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 a phenomenon that came to be known as vaccine-associated enhanced respiratory disease, in which children who had not previously been exposed to RSV and were subsequently vaccinated would develop a severe form of 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 inflammatory response during the first natural RSV infection after vaccination of RSV-naive infants. This disaster hindered vaccine development for many years to come.
A 1998 paper reported that research toward developing a vaccine had advanced greatly over the previous 10 years. Twenty years later, 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. Types of vaccines in research include particle-based vaccines, attenuated vaccines, mRNA vaccines, protein subunit vaccines, and vector-based vaccines.
In 2013, a study was published detailing the atomic-level 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, that are used in RSV vaccines. To develop its RSV vaccines, Pfizer engineered 400 different F protein constructs to identify the most immunogenic, and constructed a bivalent RSV prefusion F investigational vaccine. This structure-based design in RSV vaccines also paved the way for fast development of the COVID-19 vaccines, by providing a system to quickly determine the spike protein structure of SARS-CoV-2. As noted by Barney S. Graham, "work that had taken decades in RSV research was compressed into just a few weeks for SARS-CoV-2."
Clinical trials
, phase III trials by multiple companies were ongoing to test RSV vaccines with adults aged 60 and above. These included vaccines by GSK, Pfizer, Johnson & Johnson, Moderna, and Bavarian Nordic. multiple other vaccines are also in development, including vaccines for pregnant women to provide passive immunity via maternal antibodies to their infant, and vaccines for children.
GSK
In November 2020, GSK's vaccine, GSK3888550A, entered phase III clinical trials for pregnant women. Barney S. Graham and Peter Kwong of the National Institute of Allergy and Infectious Diseases' Vaccine Research Center, along with Jason McLellan, a former postdoctoral researcher at VRC and a professor at The University of Texas at Austin, had spearheaded its development. 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, on an account of an excess of premature births in the vaccinated group of pregnant women.
In February 2023, results of a phase III study of around 25,000 participants age 60+ were published. One dose of the vaccine provided 94% efficacy against severe RSV pneumonia and 72% efficacy against RSV acute respiratory infection. An advisory panel to the FDA recommended usage of the RSV vaccine in February 2023. In May 2023, the vaccine was approved for adults aged 60 and older, making it the first FDA-approved RSV vaccine.
The safety and effectiveness of respiratory syncytial virus vaccine, adjuvanted (Arexvy) is based on the FDA's analysis of 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 of respiratory syncytial virus vaccine, adjuvanted was designed to assess the safety and effectiveness of a single dose administered to individuals 60 years of age and older. Participants will remain in the study through three RSV seasons to assess the duration of effectiveness and the safety and effectiveness of repeat vaccination. Data for a single dose of respiratory syncytial virus vaccine, adjuvanted from the first RSV season of the study were available for the FDA's analysis. In this study, approximately 12,500 participants have received respiratory syncytial virus vaccine, adjuvanted and 12,500 participants have received a placebo. Among the participants who have received respiratory syncytial virus vaccine, adjuvanted and the participants who have received a placebo, the vaccine significantly 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.
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.
Older adults vaccine
In February 2023, the FDA's Vaccines and Related Biological Products Advisory Committee recommended to approve the RSV vaccine by Pfizer.
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 May 2023, the FDA approved the Pfizer vaccine for people 60 years and older.
Vaccine in pregnant women
In April 2023, Pfizer published the interim results of their double blind phase III study of a respiratory syncytial virus vaccine in about 3,600 pregnant women, with 3,600 women receiving a placebo. One dose of the vaccine provided 81% efficacy in preventing severe infection in the infant within three months after birth and 69% in six months after birth.
In May 2023, the FDA's expert panel unanimously recommended this vaccine for approval in pregnant women. The panel was split on the safety of the vaccine in pre-term births.
In August 2023, the FDA approved Abrysvo for use in pregnant individuals to prevent lower respiratory tract disease and severe lower respiratory tract disease caused by RSV in infants from birth through six months of age. It is approved for use at 32 through 36 weeks gestational age of pregnancy. The most common side effects were pain at the injection site, headache, muscle pain and nausea.
A clinical study evaluated the effectiveness of Abrysvo to prevent lower respiratory tract disease and severe lower respiratory tract disease caused by RSV in infants born to individuals who were vaccinated during pregnancy. Among about 3,500 pregnant individuals who received Abrysvo, compared to about 3,500 pregnant individuals who received placebo, Abrysvo reduced the risk of severe lower respiratory tract disease by 81.8% within 90 days after birth, and 69.4% within 180 days after birth. 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. The safety of Abrysvo was evaluated in two studies. In one study, about 3,600 pregnant individuals received a single dose of Abrysvo and about 3,600 pregnant individuals received a placebo. In the second study, about 100 pregnant individuals received Abrysvo and approximately 100 pregnant individuals received placebo.
Society and culture
Legal status
In March 2023, an advisory panel to the US Food and Drug Administration (FDA) recommended approval of RSV vaccines from Pfizer and GSK for older adults, based on their trial data. Both versions of the RSV vaccine were approved for medical use in the United States in May 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 to GlaxoSmithkline Biologicals S.A. 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 June 2023, Arexvy was approved for medical use in the European Union.
References
External links
Breakthrough therapy
Clinical trials
GSK plc brands
Pfizer brands
Subunit vaccines
Vaccines
Viral respiratory tract infections