Respiratory syncytial virus vaccine
Vaccine description
TargetRSVPreF3 antigen
Vaccine typeProtein subunit
Clinical data
Trade namesArexvy, Abrysvo
Other namesGSK3844766A,[1][2] respiratory syncytial virus vaccine, adjuvanted[3][4]
License data
Routes of
administration		Intramuscular
ATC code
Legal status
Legal status
Identifiers
KEGG

A respiratory syncytial virus vaccine, or RSV vaccine, is a vaccine that protects against respiratory syncytial virus.[9] RSV affects an estimated 64 million people and causes 160,000 deaths worldwide each year.[12]

The RSV vaccines Arexvy (GSK),[3] and Abrysvo (Pfizer),[6] are approved for medical use in the United States.[4][7][13] Arexvy is approved for medical use in the European Union[8][9] and in Canada for adults aged 60 or older.[14]

Research to develop an RSV vaccine continued for decades; a 2013 study led to the approved vaccines.[15][16] Work on RSV vaccines also supported the rapid development of COVID-19 vaccines.[16][17]

Abrysvo is also approved in the US for use in pregnant women at 32 through 36 weeks gestational age to protect infants from birth through six months of age.[18] Abrysvo is approved for use in pregnant women at 24 through 36 weeks and older adults in the European Union.[19][20] 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.[21]

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.[3][6][9] 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.[22]

History

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)).[23] 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.[23] 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.[23] This disaster slowed vaccine development for many years.[23]

A 1998 paper reported that research had advanced greatly over the previous 10 years.[24] 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.[25] The same study predicted that a vaccine would be available within ten years.[25] Candidates included particle-based vaccines, attenuated vaccines, mRNA vaccines, protein subunit vaccines, and vector-based vaccines.[26][27]

A 2013 study detailed the crystal structure of the RSV fusion (F) protein and how its stability could be improved.[15] This provided the basis for finding the most effective F protein constructs, which are used in RSV vaccines.[16] 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.[28]

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.[29] An advisory panel to the FDA recommended approval of the vaccine in February 2023.[30][31]

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[32][33] after review under EMA's accelerated assessment program.[32]

In May 2023, Arexvy was approved for adults aged 60 and older, making it the first FDA-approved RSV vaccine.[34][35]

In May 2023, the FDA's expert panel unanimously recommended Abrysvo for approval in pregnant women.[36] The panel was split on the safety of the vaccine in respect of preterm births.[37]

In June 2023, Arexvy was approved for medical use in the European Union.[38]

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.[39][40][41] As of April 2023, other vaccines were in development, including vaccines for pregnant women to immunize their fetuses by passing maternal antibodies to them, and vaccines for children.[16][39]

GSK

In November 2020, GSK's vaccine, GSK3888550A, entered Phase III trials for pregnant women.[42] The vaccine's antigen is a stabilized version of the RSV F protein, which was developed using structure-based vaccine design.[43][44] 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.[45]

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.[34] 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.[34] 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.[34] Data from the first RSV season of the study were available for the FDA's analysis.[34] In this study, approximately 12,500 participants received vaccine and 12,500 participants received a placebo.[34] 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%.[34] The FDA granted the application priority review designation and granted approval of Arexvy to GlaxoSmithKline Biologicals.[34]

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.[46]

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.[47][48]

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.[49] The most common side effects were pain at the injection site, headache, muscle pain and nausea.[18]

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.[18]

References

  1. ↑ "GSK starts Phase III RSV candidate vaccine programme for older adults". GSK (Press release). 16 February 2021. Archived from the original on 6 May 2023. Retrieved 6 May 2023.
  2. ↑ "GSK presents positive clinical data on maternal and older adults RSV candidate vaccines". GSK US (Press release). 21 October 2020. Archived from the original on 25 March 2023. Retrieved 6 May 2023.
  3. 1 2 3 4 "Arexvy- respiratory syncytial visus vaccine recombinant, adjuvanted kit". DailyMed. 3 May 2023. Archived from the original on 22 August 2023. Retrieved 2 June 2023.
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  5. ↑ "Summary Basis of Decision (SBD) for Arexvy". Drug and Health Products Portal. 1 September 2012. Retrieved 11 December 2023.
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  • 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
  • Clinical trial number NCT05035212 for "Study to Evaluate the Efficacy, Immunogenicity, and Safety of RSVpreF in Adults. (RENOIR)" at ClinicalTrials.gov
  • Clinical trial number NCT04424316 for "A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy" at ClinicalTrials.gov
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