Respiratory syncytial virus vaccine

Respiratory syncytial virus vaccine, or RSV vaccine, is a vaccine which prevents infection by respiratory syncytial virus. The first RSV vaccine sold under the brand name Arexvy, and developed by GSK was approved for medical use in the United States in May 2023 for people age 60 and older.

Research to develop an RSV vaccine has been ongoing for decades, with a crucial study published in 2013 that lead to the current vaccines. The work on RSV vaccines also paved the way for fast development of the COVID-19 vaccines.

Other vaccines have also been in development, including vaccines for pregnant women to provide passive immunity via maternal antibodies to their infant, and vaccines for children.

Medical uses

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

History

Development

Research to develop an RSV vaccine has been ongoing for decades, with a study published in 2013 that lead to the current 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

As of October 2022, 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. As of April 2023 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.

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.

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.

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 US Food and Drug Administration (FDA) recommended usage of the RSV vaccine at the end of February 2023. In May 2023, the vaccine was approved for adults aged 60 and older, making it the first-ever 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 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

According to a press release, "Pfizer's investigational RSV vaccine candidate builds on foundational basic science discoveries including those made at the National Institutes of Health (NIH), which detailed the crystal structure of prefusion F, a key form of the viral fusion protein (F) that RSV uses to enter human cells. The NIH research showed that antibodies specific to the prefusion form were highly effective at blocking virus infection, suggesting a prefusion F-based vaccine may confer optimal protection against RSV. After this important discovery, Pfizer tested numerous versions of a stabilized prefusion F protein and identified a candidate that elicited a strong anti-viral immune response in pre-clinical evaluations. The bivalent vaccine candidate is composed of equal amounts of recombinant RSV prefusion F from subgroups A and B."

Older adults vaccine

In April 2023, Pfizer published the 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 provided 67% efficacy in preventing infections with at least two symptoms. The vaccine 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.

The vaccine was recommended for approval by the FDA's Vaccines and Related Biological Products Advisory Committee in February 2023.

Vaccine in pregnant women

In April 2023, Pfizer published the results of their double blind phase III study of a RSV 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 3 months after birth and 69% in 6 months after birth.

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. Respiratory syncytial virus vaccine, adjuvanted was approved for medical use in the United States in May 2023.

In April 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Arexvy, intended for the prevention of Respiratory Syncytial Virus (RSV) lower respiratory tract disease in adults 60 years of age or older. Arexvy was reviewed under EMA's accelerated assessment program. The applicant for this medicinal product is GlaxoSmithkline Biologicals S.A.

External links

• Clinical trial number NCT04886596 for "Efficacy Study of GSK's Investigational Respiratory Syncytial Virus (RSV) Vaccine in Adults Aged 60 Years and Above" at ClinicalTrials.gov
• Clinical trial number NCT04732871 for "Immunogenicity, Safety, Reactogenicity and Persistence of an Investigational Respiratory Syncytial Virus (RSV) Vaccine in Adults Aged 60 Years and Above" at ClinicalTrials.gov
• Clinical trial number NCT04841577 for "A Study on the Immune Response and Safety Elicited by a Vaccine Against Respiratory Syncytial Virus (RSV) When Given Alone and Together With a Vaccine Against Influenza in Adults Aged 60 Years and Above" at ClinicalTrials.gov