Vaccinating Older and At-Risk Adults Against Respiratory Syncytial Virus

Click here to view video highlights from this interview

AJMC®: Respiratory syncytial virus (RSV) infection is often considered a childhood disease. Could you speak to this common conception and to the observed prevalence of RSV infection in adults?

WALSH: Although RSV has been recognized as a pediatric issue since the late 1950s, we’ve learned a great deal about its impact on adults during the last 30 years. Systematic studies of RSV infection in adults did not begin until around 1985. Outcomes of research, including our own studies at the University of Rochester, began to reveal that RSV was a notable cause of respiratory illness in older adults. Initially, the incidence and prevalence of RSV in adults were unclear, but as more global research has been conducted, it has become evident that RSV infection is a significant health concern in adult populations as well.

AJMC: What are the clinical characteristics of RSV infection in elderly and at-risk adults? How do these characteristics differ from those observed in pediatric patients?

WALSH: The clinical characteristics of RSV infection in adults are nonspecific and often indistinguishable from those of disease from other respiratory viruses like rhinovirus infection, influenza, or even COVID-19. Symptoms typically include runny nose, sore throat, low-grade fever, shortness of breath, and, occasionally, wheezing, particularly in those with underlying conditions such as chronic obstructive pulmonary disease (COPD) or emphysema. Unlike adults, infants with RSV frequently present with bronchiolitis that is marked by significant wheezing. Adults do not typically develop bronchiolitis due to their larger airways; however, wheezing can still be prevalent. To diagnose RSV infection accurately, specific viral diagnostic tests are necessary, as individual symptoms alone are not definitive. While epidemiological patterns show some differences—such as higher fevers generally seen in influenza compared to RSV infection—these distinctions are only evident when large groups of patients are examined. Both RSV infection and influenza tend to follow similar seasonal patterns with increased prevalence in the winter months. Although COVID-19 disrupted these patterns initially, seasonality trends for respiratory viruses including RSV are returning to their usual wintertime peaks.

AJMC: How might advanced age or other risk factors impact the pathogenesis of RSV infection in adults?

WALSH: Advanced age and other risk factors significantly impact the pathogenesis of RSV infection in adults. Individuals with reactive airway diseases such as asthma, COPD, and emphysema, as well as those with congestive heart failure, often experience more severe symptoms, including pronounced wheezing and shortness of breath. Older adults are particularly vulnerable due to a combination of factors: the accumulation of underlying medical conditions such as heart and lung diseases (especially in smokers) and a decline in immune system effectiveness with age. This immunosenescence, starting at around age 60 years and becoming more pronounced by ages 70 and 80 years, contributes to the severity of RSV infections and the presentation of more significant symptoms. These underlying medical conditions and advancing age are clear risk factors for severe RSV infection, similar to those of other viral respiratory infections.

AJMC: How safe and effective are the 3 RSV vaccines approved by the FDA for use in patients 60 years and older?^1-3

WALSH: In the past year, the FDA approved 3 RSV vaccines for adults 60 years and older. These are manufactured by GSK, Pfizer, and Moderna. They target the prefusion F protein of RSV, a crucial antigen for eliciting a strong immune response.

The vaccines show similar efficacy in preventing RSV infections. Clinical trials reveal around 60% effectiveness in preventing mild symptoms like sniffles and sore throat. For severe symptoms such as shortness of breath, troublesome cough, sputum production, and wheezing, efficacy rises to 80% to 85%. This pattern, similar to that for influenza vaccines, highlights better prevention of severe disease over total infection.

The safety profiles of these vaccines are generally favorable with some variations in adverse effects: Moderna’s mRNA vaccine is known for mild, short-lived adverse effects like sore arm, fever, and chills, which are similar to the adverse effects reported for COVID-19 messenger RNA vaccines. GSK’s protein-based vaccine contains an adjuvant also used in the shingles vaccine, leading to slightly higher occurrences of sore arm and achiness. Pfizer’s protein-based vaccine lacks an adjuvant and typically has fewer immediate adverse effects compared to GSK’s vaccine. Long-term safety monitoring is ongoing. Trials of GSK and Pfizer vaccines reported rare cases of Guillain-Barré syndrome. No such cases were reported for Moderna’s vaccine. Continued postmarketing surveillance will be essential to understanding the long-term safety profile.

AJMC: Could you describe the recommendations for RSV vaccination in older adults issued by the CDC’s Advisory Committee on Immunization Practices (ACIP) in 2023 and 2024? What was the rationale for these recommendations?⁴

WALSH: In 2023, the CDC’s ACIP issued recommendations for the use of the 3 aforementioned RSV vaccines in adults 60 years and older. These recommendations focused on balancing vaccine efficacy and safety, particularly in high-risk populations.

The RSV vaccine trials occurred during the COVID-19 pandemic, affecting both RSV incidence and trial participant behavior. This led to lower-than-expected RSV cases, as older adults adhered to COVID-19 precautions such as reduced social interactions and mask-wearing. Consequently, while the trials met efficacy end points, they did not provide substantial data on hospitalization or mortality impact due to the low incidence of severe RSV cases.

The ACIP highlighted that most trial participants were relatively healthy adults older than 60 years; few participants were older than 75 years or with significant comorbidities. This is typical for vaccine studies, which often enroll more active individuals who can attend multiple follow-up visits.

The ACIP initially recommended a targeted approach rather than a blanket recommendation for all adults older than 60 years. Physicians were asked to evaluate individual patient risk factors such as COPD, emphysema, heart failure, renal insufficiency, and age over 75 years. High-risk individuals, such as an 80-year-old lifelong smoker with emphysema, were to be prioritized for vaccination. Conversely, a healthy and active 60-year-old patient who might have had a lower risk could consider waiting for more long-term data.

The ACIP emphasized this shared decision-making between clinicians and patients. This involved discussing individual risks, benefits, and uncertainties such as the unknown frequency of booster doses. This approach contrasted with age-based vaccination guidelines such as the recommendation that everyone over 6 months old receive the annual flu shot.

The shared decision-making model presented challenges for vaccine dissemination as seen with lower uptake rates for RSV vaccines compared to flu vaccines. By April 2024, only about 20% of adults older than 60 years had received an RSV vaccine, which is similar to COVID-19 booster rates but significantly lower than flu vaccination rates (60%-70%).

During the June 2024 meeting, the ACIP altered their position and now recommends that those over 75 years, and those ages 60 to 74 years with risk factors for more severe disease (eg, heart failure, COPD, liver disease, renal failure) receive the RSV vaccine if they did not receive the vaccine last fall. The ACIP also recommends that adults residing in long term care facilities receive the vaccine.⁵

The ACIP Work Group agreed that RSV-associated disease also is likely to be a public health problem for the population aged 50 to 59 years at increased risk of severe disease. Before they make a recommendation for this population, though, the ACIP would like to see at least 1 complete season of safety surveillance data.⁶ Ongoing research and real-world evidence will inform potential adjustments to vaccination guidelines.

AJMC: What impact did the 2023 recommendations have on clinical decision-making?

WALSH: The ACIP’s 2023 recommendations for RSV vaccination in older adults emphasized shared decision-making. This approach had nuanced implications for clinical decision-making, particularly for managed care decision makers and clinicians. The concept of shared decision-making is relatively novel in vaccination practices. Traditionally, vaccines like those for influenza and shingles are recommended broadly based on age or other clear criteria. Shared decision-making requires both physicians and patients to understand the disease, the vaccine’s benefits, and its risks. This approach may have been challenging for clinicians unfamiliar with this model, which could have impacted vaccine uptake.

Different countries have adopted varying strategies. For example, the United Kingdom has opted for an age-based recommendation, vaccinating everyone aged over 75 years. While this simplifies administration, it may overlook high-risk individuals aged 60 to 74 years. In contrast, the US approach emphasizes risk factors, potentially leading to more tailored and equitable health care outcomes. The ACIP’s focus on high-risk conditions rather than age alone aims to address disparities. Data show significant portions of those hospitalized with RSV are younger than 60 years, with higher rates noted among Black populations. A risk-based approach helps mitigate these disparities, ensuring that those most vulnerable receive the vaccine regardless of age.

AJMC: What are the implications of the ACIP’s 2024 recommendations for public health practice? How might the guidance combat the clinical burden of RSV in the older adult population?

WALSH: The ACIP’s recommendations on RSV vaccination hold significant weight in shaping public health strategies, especially regarding vaccine adoption in older adults. This guidance influences both individual clinical decisions and organizational health care policies. Managed care decision makers, including large health care systems like Kaiser Permanente, are guided by ACIP recommendations. These directives influence administrative decisions that subsequently guide physicians in their clinical practices. The thoughtful consideration of vaccine benefits and public health impact underscores the importance of these recommendations. The effectiveness of RSV vaccines in real-world scenarios is currently being evaluated through ongoing studies by the CDC, and preliminary data are highly supportive of reasonable efficacy in those groups recommended to receive the vaccines. These studies focus on outcomes such as hospitalizations and office visits among vaccinated populations. Initial predictions suggest a substantial reduction in hospitalizations, potentially up to 75% in certain high-risk groups. Data accumulated over the next few years will likely bolster recommendations and policies surrounding vaccine use.

Nursing homes, despite being highly susceptible environments for RSV outbreaks, were underrepresented in initial vaccine trials. This raised concerns among nursing home directors regarding vaccine efficacy and suitability for their residents. To address these concerns, studies were designed to assess vaccine immunogenicity in nursing home populations. These immunobridging studies aim to demonstrate that the vaccine induces protective antibody responses similar to those seen in healthier populations, thereby justifying widespread vaccination in this vulnerable group. Based on results of these studies, the CDC now recommends that adults in nursing homes receive an RSV vaccination.

Determining the optimal vaccination interval for RSV remains a key consideration. Initial studies showed efficacy over 2 years, yet questions linger about the need for annual, biennial, or triennial vaccinations. Variability in vaccination policies among nursing homes, particularly for influenza vaccines, underscores the logistical challenges of implementing new vaccine strategies in long-term care settings.

The ACIP’s 2023 and 2024 recommendations on RSV vaccination represent a pivotal step in combatting the clinical burden of RSV in older adults. These guidelines aim to optimize public health outcomes while navigating logistical and clinical challenges unique to different health care settings. As ongoing research refines our understanding of vaccine effectiveness and administration strategies, future updates will likely further enhance these recommendations to better protect vulnerable populations.

AJMC: On June 7, 2024, the FDA expanded the indication for 1 RSV vaccine to include adults aged 50 to 59 years who are at increased risk for lower respiratory tract disease (LRTD) caused by RSV.^2,7 What is the clinical significance of this expansion?

WALSH: The expansion follows a request by GSK to extend vaccination eligibility to individuals aged 50 to 59 years who have high-risk conditions. This broader age criterion acknowledges the significant risk posed by RSV-related LRTD in adults beyond traditional high-risk thresholds. While the initial focus is on adults aged 50 to 59 years, there is growing anticipation for similar expansions with other RSV vaccines. The potential benefits extend beyond this age bracket, as younger adults with severe lung disease have also demonstrated vulnerability to RSV-related hospitalizations. Despite excluding immunocompromised individuals from initial trials, ongoing studies are now evaluating vaccine efficacy in these high-risk groups. This critical research aims to establish immune response patterns and optimize vaccination strategies for populations like organ transplant recipients and those on immunosuppressive therapies.

As new data emerge from studies of immunocompromised patients in the coming year, they will inform subsequent recommendations to integrate these vaccines into clinical practice guidelines. This iterative process underscores the evolving nature of vaccine deployment and the ongoing need for comprehensive data to guide inclusive vaccination strategies.

The FDA’s decision to expand the RSV vaccine’s indication represents a significant stride in combatting RSV-related LRTD across broader adult populations. As efforts continue to refine vaccine efficacy and deployment strategies, ongoing research remains pivotal in addressing the diverse clinical needs posed by RSV, ensuring equitable access and optimized protection for all at-risk groups.

AJMC: When should elderly and at-risk adults get vaccinated?

WALSH: As RSV resumes its typical seasonal patterns, understanding the optimal timing for vaccination among elderly and at-risk adults is crucial for effective preventive care strategies. RSV traditionally resurfaces in the fall, with Florida and the Gulf Coast typically seeing cases in September followed by northern regions like Rochester, New York, around Thanksgiving. This pattern is expected to repeat this year albeit with regional variations in timing. For residents in Rochester and similar northern areas, vaccination is ideally scheduled for September or October, aligning with the onset of local RSV activity. Conversely, individuals in southern regions should aim for vaccination in August or September, anticipating earlier seasonal outbreaks. RSV vaccines provide robust antibody responses lasting 6 to 8 months or potentially longer, maintaining protective levels against severe disease. Unlike influenza vaccines, which may wane in efficacy if administered too early, RSV vaccine efficacy remains relatively stable over the season. Current guidelines do not recommend annual boosters for RSV vaccines. Individuals vaccinated within the past year do not require immediate revaccination unless otherwise indicated by specific risk factors or changing health conditions.

The optimal time for elderly and at-risk adults to receive RSV vaccination aligns with the onset of seasonal activity in their respective regions, which typically occurs in the fall. This approach ensures maximal protection during peak transmission periods while minimizing the risk of waning vaccine effectiveness later in the season. As seasonal patterns normalize, adherence to these timing recommendations will be pivotal in mitigating the clinical burden of RSV and enhancing public health outcomes.

AJMC: In elderly and at-risk populations, can RSV vaccines be co-administered with other vaccines?

WALSH: From a practical standpoint, simultaneous administration of multiple vaccines in adults offers significant convenience, considering that they have fewer doctor visits compared with infants and children. RSV vaccines, including those for influenza, can be safely co-administered without notable interference or safety concerns. Currently, while concurrent administration of COVID-19, influenza, and RSV vaccines is not recommended based on existing data, anecdotal reports suggest that some individuals have received all 3 vaccines simultaneously without adverse effects. However, formal recommendations await comprehensive data analysis to ensure safety and efficacy in such combinations.

Looking ahead, as research progresses on respiratory viruses affecting adults—similar to what is well-established in children for RSV and influenza—there is growing interest in developing vaccines targeting multiple pathogens in a single formulation. Technologies like messenger RNA vaccines show promise in facilitating multiantigen formulations, potentially paving the way for combined vaccines against influenza, RSV, human metapneumovirus, parainfluenza virus, and others in the future.

Laboratories and pharmaceutical companies are actively exploring these possibilities, aiming to streamline vaccination strategies for adult populations against respiratory viruses and enhance convenience and efficacy in preventive health care practices.

AJMC: What final thoughts do you have about these recommendations?

WALSH: The critical next step in assessing RSV vaccines is evaluating their real-world effectiveness over the coming year. These data will be pivotal in determining the cost-effectiveness and overall value of widespread RSV vaccination efforts. As this information is currently being gathered, staying updated on these findings will be crucial for informed decision-making among managed care professionals and clinicians. Understanding the true impact of these vaccines in practice will guide resource allocation and strategic health care planning moving forward.

REFERENCES

1. Abrysvo. Prescribing information. Pfizer; 2024. Accessed June 12, 2024. https://labeling.pfizer.com/ShowLabeling.aspx?id=19589

2. Arexvy. Prescribing information. GlaxoSmithKline; 2024. Accessed June 12, 2024. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Arexvy/pdf/AREXVY.PDF

3. mRESVIA. Prescribing information; Moderna. 2024. Accessed June 12, 2024. https://static.modernatx.com/pm/6cef78f8-8dad-4fc9-83d5-d2fbb7cff867/36130c97-6fb0-4bea-9f2e-fb5be7a90729/36130c97-6fb0-4bea-9f2efb5be7a90729_viewable_rendition__v.pdf

4. Melgar M, Britton A, Roper LE, et al. Use of respiratory syncytial virus vaccines in older adults: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(29):793-801. doi:10.15585/mmwr.mm7229a4

5. CDC updates RSV vaccination recommendation for adults. CDC. June 26, 2024. Accessed June 27, 2024. https://www.cdc.gov/media/releases/2024/s-0626-vaccination-adults.html

6. Britton A, Melgar M, Roper L. Evidence to recommendations framework (EtR): RSV vaccination in adults aged 50–59 years, 60–74 years, and 75 years and older. CDC. June 26, 2024. Accessed July 3, 2024. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-06-26-28/11-RSV-Adult-Melgar-Roper-Britton-508.pdf

7. BL 125775/132 supplement approval. FDA. June 7, 2024. Accessed June 12, 2024. https://www.fda.gov/media/179248/download?attachment