We are entering the 2024-25 RSV season with more tools to prevent respiratory syncytial virus (RSV) infections than ever before:
- Three options for older adults, including two recombinant vaccines and an mRNA vaccine
- Two monoclonal antibodies to provide passive immunization to newborns and high-risk older infants
- One maternal vaccine administered during pregnancy for the purpose of passing maternal antibodies to the baby before birth
New tools continue to be studied after licensure. These additional studies enable us to learn about real-world effectiveness and rare safety concerns that were not detected in clinical trials. At times, the Food and Drug Administration (FDA) will also request specific data after a vaccine is licensed if clinical trials raised a particular question or issue. For example, in the case of RSV vaccine during pregnancy, some evidence of preterm delivery led to a request for additional studies related to this matter. With one RSV season using these tools under our collective belt, we thought it would be helpful to review some lessons learned. In this issue, we will focus on the products for infants, and in the September issue, we will focus on the lessons learned related to RSV vaccines for adults.
How effectively does nirsevimab reduce hospitalizations for RSV in the real world?
Clinical trials are designed to test a vaccine under the best conditions. Before a vaccine is licensed, large clinical trials, known as phase 3 studies, determine how well the vaccine is working under optimal conditions; the outcomes are reported as vaccine efficacy. However, when that vaccine is given to the population at large, it may not work as well because many different people are administering the vaccine to a much more diverse group of recipients in a large variety of conditions. For this reason, post-licensure studies (called phase 4 studies) monitor the real-world utility of the vaccine, known as vaccine effectiveness.
The phase 3 clinical trials of nirsevimab found a vaccine efficacy of about 90% against hospitalization for RSV-associated lower respiratory tract infection.In the past year, real-world studies were completed, finding a similar vaccine effectiveness:
- A study of 1,035 infants in France, published in The New England Journal of Medicine, documented real-world effectiveness of 83% against hospitalization for RSV-associated bronchiolitis.
- A study of 699 infants hospitalized with acute respiratory illness in the New Vaccine Surveillance Network in the United States, published in Morbidity and Mortality Weekly Report (MMWR), documented early estimates of 90% effectiveness.
- A population-based study of 10,259 infants in Galecia, Spain, published in Lancet Infectious Diseases, reported an effectiveness of 82% against hospitalization.
If children receive nirsevimab, will the burden of RSV disease shift to the second year of life?
The short answer is no, but where did this question come from?
During COVID-19, lockdowns and distancing aimed at decreasing the spread of SARS-CoV-2 virus also decreased the spread of other respiratory viruses, including RSV. As a result, a cohort of children was not exposed to or infected with RSV during their first year of life, leading to a surge in hospitalizations as many children experienced their first infections during their second RSV season. Some then wondered if offering nirsevimab to limit infections in an infant’s first RSV season would similarly shift the burden of disease to a child’s second RSV season. Reassuringly, studies have demonstrated this not to be a concern:
- A study of 3,012 infants was published in the Journal of the Pediatric Infectious Diseases Society. Infants were randomized to receive either placebo or nirsevimab, and they were followed through their second RSV season. In both groups, only 1.0% had an RSV infection of the lower respiratory tract that required medical intervention during their second RSV season, demonstrating that receiving nirsevimab did not shift infections to the next season after receiving antibody.
- An additional study, reported in Nature Medicine, analyzed serum samples from 2,143 infants one year after receiving either nirsevimab or placebo. The babies had similar rates of antibodies against an RSV protein not recognized by the monoclonal antibody nirsevimab, which recognizes only one part of the RSV surface protein. This indicated that nirsevimab protected babies from getting ill, but they were still exposed to RSV in the first year of life and their immune systems responded to those exposures, so they were protected during their second season.
Does the maternal vaccine, Abrysvo, lead to increases in premature births?
In the pre-licensure studies of Abrysvo, a greater number of premature births occurred in the vaccine group compared with the placebo group. Although not statistically significant, the finding was most notable in low- and middle-income countries. In response to this finding, the vaccine was approved for use only during the period of 32 through 36 weeks of gestation while additional studies were conducted. The first published study is reassuring. In a cohort study, published in JAMA Network Open, 2,973 pregnant individuals who delivered at 32 weeks gestation or later were evaluated. Preterm births occurred in 5.9% of vaccinated individuals compared with 6.7% of those who were not vaccinated. Preliminary data from the Vaccine Safety Datalink (VSD), one of the vaccine monitoring programs of the Centers for Disease Control and Prevention (CDC), have also been reassuring; analysis from this system is ongoing.
How will patients and families access these immunizations?
Last season’s implementation had many logistical challenges. While this season is likely to go more smoothly, some implementation processes continue to evolve. Regional collaborations will be important for ensuring that patients and families can access these life-saving tools for infants.
Expected improvements for 2024-2025
- Supply of both maternal vaccine and nirsevimab should be robust, including having a better supply of the different nirsevimab doses.
- The Vaccines for Children (VFC) program, Medicaid, and most private insurers will cover these products.
Continuing to evolve in 2024-2025
- Maternal vaccine can be accessed at primary care providers, obstetricians, retail pharmacies, and some health centers.
- Infant monoclonal antibody can be accessed at some, but not all, birthing hospitals as well as from primary care providers and at some health centers. The VFC program team is continuing to work with birthing hospitals to increase the number that can offer VFC doses of nirsevimab to newborns. Importantly for local healthcare providers who see newborns, as tals can offer VFC doses of nirsevimab, so this is an example where knowing your local landscape will be important.
- Healthcare providers for newborns continue to lack access to maternal health records, making it difficult to know if an infant is protected due to maternal immunization.
Overall, the data from the past year are reassuring and offer healthcare providers more information, positioning all of us to provide strong recommendations to families this fall. While we will see additional studies this season, it is also likely that we will begin to see measurable impacts of these new tools as coverage improves and we are able to protect the most vulnerable among us.
Resources
- Respiratory Syncytial Virus (RSV) Vaccine and Monoclonal Antibody
- Advisory Committee on Immunization Practices Slides: Maternal RSV vaccine safety surveillance
- Advisory Committee on Immunization Practices Slides: Summary of effectiveness of nirsevimab infants
Contributed by: Lori Handy, MD, MSCE , Charlotte A. Moser, MS, Paul A. Offit, MD
We are entering the 2024-25 RSV season with more tools to prevent respiratory syncytial virus (RSV) infections than ever before:
- Three options for older adults, including two recombinant vaccines and an mRNA vaccine
- Two monoclonal antibodies to provide passive immunization to newborns and high-risk older infants
- One maternal vaccine administered during pregnancy for the purpose of passing maternal antibodies to the baby before birth
New tools continue to be studied after licensure. These additional studies enable us to learn about real-world effectiveness and rare safety concerns that were not detected in clinical trials. At times, the Food and Drug Administration (FDA) will also request specific data after a vaccine is licensed if clinical trials raised a particular question or issue. For example, in the case of RSV vaccine during pregnancy, some evidence of preterm delivery led to a request for additional studies related to this matter. With one RSV season using these tools under our collective belt, we thought it would be helpful to review some lessons learned. In this issue, we will focus on the products for infants, and in the September issue, we will focus on the lessons learned related to RSV vaccines for adults.
How effectively does nirsevimab reduce hospitalizations for RSV in the real world?
Clinical trials are designed to test a vaccine under the best conditions. Before a vaccine is licensed, large clinical trials, known as phase 3 studies, determine how well the vaccine is working under optimal conditions; the outcomes are reported as vaccine efficacy. However, when that vaccine is given to the population at large, it may not work as well because many different people are administering the vaccine to a much more diverse group of recipients in a large variety of conditions. For this reason, post-licensure studies (called phase 4 studies) monitor the real-world utility of the vaccine, known as vaccine effectiveness.
The phase 3 clinical trials of nirsevimab found a vaccine efficacy of about 90% against hospitalization for RSV-associated lower respiratory tract infection.In the past year, real-world studies were completed, finding a similar vaccine effectiveness:
- A study of 1,035 infants in France, published in The New England Journal of Medicine, documented real-world effectiveness of 83% against hospitalization for RSV-associated bronchiolitis.
- A study of 699 infants hospitalized with acute respiratory illness in the New Vaccine Surveillance Network in the United States, published in Morbidity and Mortality Weekly Report (MMWR), documented early estimates of 90% effectiveness.
- A population-based study of 10,259 infants in Galecia, Spain, published in Lancet Infectious Diseases, reported an effectiveness of 82% against hospitalization.
If children receive nirsevimab, will the burden of RSV disease shift to the second year of life?
The short answer is no, but where did this question come from?
During COVID-19, lockdowns and distancing aimed at decreasing the spread of SARS-CoV-2 virus also decreased the spread of other respiratory viruses, including RSV. As a result, a cohort of children was not exposed to or infected with RSV during their first year of life, leading to a surge in hospitalizations as many children experienced their first infections during their second RSV season. Some then wondered if offering nirsevimab to limit infections in an infant’s first RSV season would similarly shift the burden of disease to a child’s second RSV season. Reassuringly, studies have demonstrated this not to be a concern:
- A study of 3,012 infants was published in the Journal of the Pediatric Infectious Diseases Society. Infants were randomized to receive either placebo or nirsevimab, and they were followed through their second RSV season. In both groups, only 1.0% had an RSV infection of the lower respiratory tract that required medical intervention during their second RSV season, demonstrating that receiving nirsevimab did not shift infections to the next season after receiving antibody.
- An additional study, reported in Nature Medicine, analyzed serum samples from 2,143 infants one year after receiving either nirsevimab or placebo. The babies had similar rates of antibodies against an RSV protein not recognized by the monoclonal antibody nirsevimab, which recognizes only one part of the RSV surface protein. This indicated that nirsevimab protected babies from getting ill, but they were still exposed to RSV in the first year of life and their immune systems responded to those exposures, so they were protected during their second season.
Does the maternal vaccine, Abrysvo, lead to increases in premature births?
In the pre-licensure studies of Abrysvo, a greater number of premature births occurred in the vaccine group compared with the placebo group. Although not statistically significant, the finding was most notable in low- and middle-income countries. In response to this finding, the vaccine was approved for use only during the period of 32 through 36 weeks of gestation while additional studies were conducted. The first published study is reassuring. In a cohort study, published in JAMA Network Open, 2,973 pregnant individuals who delivered at 32 weeks gestation or later were evaluated. Preterm births occurred in 5.9% of vaccinated individuals compared with 6.7% of those who were not vaccinated. Preliminary data from the Vaccine Safety Datalink (VSD), one of the vaccine monitoring programs of the Centers for Disease Control and Prevention (CDC), have also been reassuring; analysis from this system is ongoing.
How will patients and families access these immunizations?
Last season’s implementation had many logistical challenges. While this season is likely to go more smoothly, some implementation processes continue to evolve. Regional collaborations will be important for ensuring that patients and families can access these life-saving tools for infants.
Expected improvements for 2024-2025
- Supply of both maternal vaccine and nirsevimab should be robust, including having a better supply of the different nirsevimab doses.
- The Vaccines for Children (VFC) program, Medicaid, and most private insurers will cover these products.
Continuing to evolve in 2024-2025
- Maternal vaccine can be accessed at primary care providers, obstetricians, retail pharmacies, and some health centers.
- Infant monoclonal antibody can be accessed at some, but not all, birthing hospitals as well as from primary care providers and at some health centers. The VFC program team is continuing to work with birthing hospitals to increase the number that can offer VFC doses of nirsevimab to newborns. Importantly for local healthcare providers who see newborns, as tals can offer VFC doses of nirsevimab, so this is an example where knowing your local landscape will be important.
- Healthcare providers for newborns continue to lack access to maternal health records, making it difficult to know if an infant is protected due to maternal immunization.
Overall, the data from the past year are reassuring and offer healthcare providers more information, positioning all of us to provide strong recommendations to families this fall. While we will see additional studies this season, it is also likely that we will begin to see measurable impacts of these new tools as coverage improves and we are able to protect the most vulnerable among us.
Resources
- Respiratory Syncytial Virus (RSV) Vaccine and Monoclonal Antibody
- Advisory Committee on Immunization Practices Slides: Maternal RSV vaccine safety surveillance
- Advisory Committee on Immunization Practices Slides: Summary of effectiveness of nirsevimab infants
Contributed by: Lori Handy, MD, MSCE , Charlotte A. Moser, MS, Paul A. Offit, MD