Abstract

Respiratory syncytial virus (RSV) is a major cause of respiratory illness and hospitalization in older adults during fall and winter in the United States. The 2023–2024 RSV season was the first during which RSV vaccination was recommended for U.S. adults aged ≥60 years, using shared clinical decision-making. On June 26, 2024, the Advisory Committee on Immunization Practices voted to update this recommendation as follows: a single dose of any Food and Drug Administration–approved RSV vaccine (Arexvy [GSK]; Abrysvo [Pfizer]; or mResvia [Moderna]) is now recommended for all adults aged ≥75 years and for adults aged 60–74 years who are at increased risk for severe RSV disease. Adults who have previously received RSV vaccine should not receive another dose. This report summarizes the evidence considered for these updated recommendations, including postlicensure data on vaccine effectiveness and safety, and provides clinical guidance for the use of RSV vaccines in adults aged ≥60 years. These updated recommendations are intended to maximize RSV vaccination coverage among persons most likely to benefit, by clarifying who is at highest risk and by reducing implementation barriers associated with the previous shared clinical decision-making recommendation. Continued postlicensure monitoring will guide future recommendations.

Introduction

Respiratory syncytial virus (RSV) is a major cause of respiratory illness and hospitalizations in older adults during fall and winter in the United States (1). On June 21, 2023, CDC’s Advisory Committee on Immunization Practices (ACIP) issued its first adult RSV vaccination recommendation, stating that adults aged ≥60 years may receive a single dose of RSV vaccine, using shared clinical decision-making (2).

As of spring 2024, 20%–25% of U.S. adults aged ≥60 years were estimated to have received RSV vaccine,* and the first postlicensure safety and effectiveness data for GSK’s Arexvy and Pfizer’s Abrysvo became available.^† In addition, on May 31, 2024, the Food and Drug Administration (FDA) approved a third RSV vaccine (mResvia [Moderna]) for prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) in adults aged ≥60 years^§ (3,4).

To update adult RSV vaccination recommendations, ACIP considered data from previous meetings; new data from randomized, observer-blind, placebo-controlled clinical trials (RCTs) of mResvia; and postlicensure data on Arexvy and Abrysvo. This report summarizes that evidence and presents updated ACIP recommendations for RSV vaccination in adults aged ≥60 years.^¶

Methods

The ACIP Work Group for RSV prevention in adults met at least monthly since July 2023 to consider updates to adult RSV vaccination recommendations, using the Evidence to Recommendation Framework (EtR) to guide its deliberations.** Work Group conclusions were publicly presented to ACIP on June 26, 2024. Full details for Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) are available at https://www.cdc.gov/vaccines/acip/recs/grade/mrna-rsv-vaccine-older-adults.html and https://www.cdc.gov/vaccines/acip/recs/grade/protein-subunit-rsv-vaccines-older-adults.html and for EtR are available at https://www.cdc.gov/vaccines/acip/recs/grade/mrna-rsv-vaccine-older-adults-etr.html and https://www.cdc.gov/vaccines/acip/recs/grade/protein-subunit-rsv-vaccines-older-adults-etr.html.

Vaccine Efficacy and Safety

mRNA RSV Vaccine (Moderna mResvia)

In considering recommendations for use of Moderna’s mResvia, ACIP reviewed data from two RCTs. A phase 2/3 trial contributed safety and efficacy data from 36,685 immunocompetent participants aged ≥60 years who received a single dose of mResvia (50 μg of mRNA encoding the prefusion RSV F protein) or saline placebo; participants were enrolled on a rolling basis during November 2021–December 2022 (Moderna, mRNA-1345 phase 2/3 clinical trial, unpublished data, 2024) (5). A phase 1 trial contributed additional safety data from 106 participants aged 65–79 years who received either the phase 2/3 trial vaccine formulation or placebo (6).

Vaccine efficacy. In Moderna’s primary efficacy analysis (median per participant postvaccination follow-up time = 3.7 months; range = 0.5–12.6 months), efficacy of 1 dose was 78.7% (95% CI = 62.8%–87.9%) in preventing symptomatic, laboratory-confirmed RSV-LRTD with two or more lower respiratory symptoms and 80.9% (95% CI = 50.1%–92.7%) in preventing RSV-LRTD with three or more lower respiratory symptoms^†† (Table 1) (7). Using all available follow-up time (median = 18.8 months per participant; range = 0.5–24 months), efficacy of mResvia was 47.4% (95% CI = 35.0%–57.4%) against RSV-LRTD with two or more symptoms and 48.4% (95% CI = 27.9%–63.1%) against RSV-LRTD with three or more symptoms (Moderna, mRNA-1345 phase 2/3 clinical trial, unpublished data, 2024) (7).

Efficacy point estimates were higher during the first 12 months after vaccination compared with the subsequent 12 months. The trial was not powered to estimate efficacy against medically attended RSV illness, including hospitalization, or RSV-associated death.

Vaccine safety. Severe reactogenicity events were more common among mResvia recipients than among placebo recipients^§§ (pooled relative risk = 1.54 [95% CI = 1.40–1.68]); (Supplementary Table, https://stacks.cdc.gov/view/cdc/159161) (4). The pooled relative risk for serious adverse events comparing the intervention and control groups was 1.00 (95% CI = 0.95–1.05).^¶¶ No cases of Guillain-Barré syndrome (GBS), other inflammatory neurologic events, myocarditis, or pericarditis were recorded within 42 days after mResvia vaccination.

Protein Subunit RSV Vaccines (GSK Arexvy and Pfizer Abrysvo)

Vaccine effectiveness. Postlicensure data were reviewed from four observational studies of vaccine effectiveness (VE) of protein subunit RSV vaccination against RSV-associated hospitalization among adults aged ≥60 years during the first RSV season after vaccination***; estimates from the general population or among immunocompetent adults only ranged from 75% (95% CI = 50%–87%) to 82% (95% CI = 69%–89%) (8). VE was similar across vaccine products (GSK Arexvy and Pfizer Abrysvo) and patient age groups (60–74 years and ≥75 years). In addition, effectiveness was demonstrated among adults aged ≥60 years with certain immunocompromising conditions^††† and those with end-stage renal disease.

Vaccine safety: Guillain-Barré syndrome. Postlicensure safety data were reviewed from an FDA self-controlled case series analysis estimating risk for GBS attributable to protein subunit RSV vaccination among Medicare beneficiaries aged ≥65 years (9). The analysis compared GBS incidence during a risk interval (days 1–42 postvaccination) with that during a control interval (days 43–90 postvaccination). Among beneficiaries vaccinated before October 8, 2023, the GBS adjusted incidence rate ratio in the risk interval versus the control interval was 2.30 (95% CI = 0.39–13.72) for GSK’s Arexvy and 4.48 (95% CI = 0.88–22.90) for Pfizer’s Abrysvo. In this analysis, GBS cases were identified using medical claims data and were not yet confirmed by review of medical records; a final analysis will incorporate medical record review for confirmation of GBS diagnoses and will include additional adults vaccinated later in the 2023–2024 RSV season. Overall, results from this initial analysis did not provide clear, conclusive evidence of an elevated risk for GBS associated with RSV vaccination in older adults, but an elevated risk of GBS could not be ruled out. GBS safety surveillance is ongoing and additional analyses are underway.

Vaccine safety: immune thrombocytopenia. Results of rapid cycle analysis performed by the Vaccine Safety Datalink^§§§ demonstrated a statistical signal for immune thrombocytopenia (ITP) in a risk interval (days 1–21) after GSK Arexvy vaccination, without simultaneous receipt of another vaccine, compared with a comparison interval (days 22–42)^¶¶¶ (10). However, medical record review revealed that onset of most ITP cases occurred before vaccination; onset after vaccination occurred in only four cases identified during the risk interval and one case during the comparison interval. Because of the small number of cases, an association cannot be confirmed between GSK Arexvy vaccination and ITP; supplementary evaluation of identified cases and monitoring for additional cases are ongoing.

Balance of benefits and risks. In a modeling study, estimated public health benefits of protein subunit RSV vaccination were compared with potential GBS risk. Benefits were estimated using observational VE, surveillance data on incidence of RSV-associated outcomes, and RCT evidence of duration of vaccine-conferred protection; risk for GBS was estimated from the FDA self-controlled case series analysis (11). Estimated RSV-associated hospitalizations, intensive care unit admissions, and deaths preventable over two consecutive RSV seasons per 1 million RSV vaccine doses administered exceeded estimated numbers of potential vaccine-attributable GBS cases but varied by age and risk group (Table 2). Study limitations included inability to evaluate all risk factors that might be associated with severe RSV disease, uncertainty in VE beyond 4 months postvaccination, and estimates of GBS risk based on few identified cases.

Recommendations for Use of RSV Vaccines for Prevention of RSV-Associated Disease in Adults Aged ≥60 Years

On June 26, 2024, ACIP recommended a single dose of any FDA-approved RSV vaccine for all adults aged ≥75 years and for adults aged 60–74 years who are at increased risk for severe RSV disease.**** Adults who have previously received RSV vaccine should not receive another dose. Adults aged 60–74 years who are at increased risk include persons with certain chronic medical conditions, persons with moderate or severe immune compromise, and persons living in nursing homes (Box). These recommendations replace the June 2023 shared clinical decision-making recommendation for RSV vaccination for adults aged ≥60 years and apply to all RSV vaccines licensed for adults aged ≥60 years (i.e., Arexvy [GSK], Abrysvo [Pfizer], or mResvia [Moderna]).

Qualified vaccinators, including pharmacists, nurse practitioners, and other providers (based on state and jurisdictional law) may determine patient eligibility for RSV vaccination based on clinical assessment even in the absence of medical documentation of a named risk condition. Patient attestation is sufficient evidence of the presence of a risk factor; vaccinators should not deny RSV vaccination to a person because of lack of documentation. These factors should be considered to optimize patient access, including in administrative procedures, such as reimbursement policies for RSV vaccination.

Rationale for Recommendations

The 2023 shared clinical decision-making RSV vaccination recommendation was made in the setting of uncertainty in some portions of the evidence profile. RCTs of both protein subunit vaccines (GSK Arexvy and Pfizer Abrysvo) were underpowered to demonstrate protection against RSV-associated hospitalization or death, and enrolled few participants who were frail or aged ≥75 years. Although both vaccines were well-tolerated and exhibited an acceptable safety profile, a small number of inflammatory neurologic events, including GBS, were observed after RSV vaccination in clinical trials. Because of the small number of GBS cases in the trials, it was unclear whether they represented an association between RSV vaccination and GBS or occurred because of chance alone. Acknowledging these uncertainties, in June 2023 ACIP recommended shared clinical decision-making to encourage providers and patients to consider individual risk of RSV disease (2); however, shared clinical decision-making has drawbacks. Providers find it confusing and time-consuming to implement (12,13). After one season of RSV vaccine availability, vaccination coverage among adults with chronic medical conditions has been only modestly higher than that among adults without conditions (14). The challenges of shared clinical decision-making, along with the updated evidence on balance of benefits and risks, led ACIP in June 2024 to make an age-based recommendation for adults aged ≥75 years and a risk-based recommendation for those aged 60–74 years. These updated recommendations are intended to maximize RSV vaccination coverage among persons most likely to benefit, by clarifying who is at highest risk and by reducing implementation barriers associated with the previous shared clinical decision-making recommendation (15).

ACIP recognized that a risk-based recommendation for adults aged 60–74 years might result in lower RSV vaccination coverage among persons at increased risk compared with an age-based recommendation for this group (16). However, ACIP judged that postlicensure safety surveillance suggests a potential increased risk for GBS after protein subunit RSV vaccination (GSK Arexvy and Pfizer Abrysvo), and although no GBS signal was observed after Moderna mResvia vaccination in RCTs, postlicensure safety surveillance has yet to occur. Based on currently available evidence, ACIP concluded that the benefits of RSV vaccination did not clearly outweigh the potential harms in adults aged 60–74 years without risk factors for severe RSV disease. However, ACIP also stressed that research regarding RSV risk factors is ongoing, so providers should continue to have flexibility in offering RSV vaccine to patients they assess to be at increased risk for severe disease even if they do not fall into an explicitly named risk category. As with all vaccines, patients should be informed of the benefits and risks of RSV vaccination (17); for protein subunit RSV vaccines, this information includes potential risk for GBS.

Clinical Guidance

Administration of RSV vaccine with other adult vaccines during the same visit is acceptable. Additional information regarding coadministration and regarding contraindications and precautions is available at https://www.cdc.gov/vaccines/vpd/rsv/hcp/older-adults.html.

Timing of RSV Vaccination

Eligible adults are currently recommended to receive a single dose of RSV vaccine; adults who have already received RSV vaccination should not receive another dose. A single dose provides protection for at least two RSV seasons. The need for additional RSV vaccine doses will be evaluated by ACIP in the future; ACIP will update recommendations as needed.

Eligible adults who have not previously received RSV vaccination may be vaccinated at any time of year, but vaccination will have the most benefit if administered in late summer or early fall, just before the RSV season. In most of the continental United States, this corresponds to vaccination during August–October.

Reporting of Vaccine Adverse Events

Adverse events after vaccination should be reported to the Vaccine Adverse Event Reporting System (VAERS). Reporting of any clinically significant adverse event is encouraged, even if it is uncertain whether the vaccine caused the event. Information on how to submit a report to VAERS is available at https://vaers.hhs.gov/index.html or by telephone at 1-800-822-7967.

Future RSV Vaccine Policy for Adults

On June 7, 2024, FDA approved use of GSK’s Arexvy in adults aged 50–59 years who are at increased risk for RSV-LRTD (18). As of June 2024, ACIP judged that insufficient evidence was available to inform a vote on RSV vaccination policy in adults aged 50–59 years who are at increased risk for RSV disease. Before voting on a recommendation in this age group, ACIP expressed that the following items are needed: updated RSV vaccine safety analyses among adults aged ≥60 years, including results from the full 2023–2024 RSV season in the FDA analysis incorporating chart confirmation of GBS diagnoses; additional data on duration of protection from RSV vaccination and immune response after revaccination; and immunogenicity data in adults with immunocompromise. ACIP will review evidence and vote on RSV vaccination policy in this age group when additional data are available.