RSV immunization in adults and children: A practical guide for clinicians

RSV IS A MAJOR PUBLIC HEALTH PROBLEM

RSV is a leading cause of respiratory tract illness in all age groups in the United States. In healthy adults, RSV infection is typically associated with mild respiratory symptoms such as rhinorrhea, cough, sneezing, or fever.¹ However, in young children and older adults, it can be a more serious illness associated with high rates of hospitalization and increased mortality.

In the United States, RSV infection leads to approximately 2.1 million outpatient visits and 58,000 to 80,000 hospitalizations per year among children less than 5 years of age, and an estimated 60,000 to 160,000 hospitalizations in adults 65 years of age or older.² Compared with other respiratory viral illnesses, RSV infection may be less common but more severe, with higher odds of invasive mechanical ventilation or death than with influenza and COVID-19.³

With no direct-acting treatments, RSV management is typically limited to supportive care, further demonstrating the need for RSV immunizations.

ACTIVE AND PASSIVE IMMUNIZATION

Immunizations fall into 2 groups: passive immunization with monoclonal antibodies, and active immunization with vaccines.

EFFICACY AND SAFETY OF RSV MONOCLONAL ANTIBODIES

EFFICACY AND SAFETY OF RSV VACCINES

POSTMARKETING SURVEILLANCE ONGOING

The current FDA-approved RSV immunizations are safe and unlikely to cause serious adverse events. Postmarketing safety surveillance will provide additional insights on immunization safety. Clinicians should report adverse reactions to nirsevimab and palivizumab through the FDA MedWatch program online, by mail, by fax, or by calling 1-800-FDA-1088. Vaccine-related reactions, including reactions to nirsevimab or palivizumab when coadministered with a non-RSV vaccine, should be reported to the Vaccine Adverse Event Reporting System (VAERS) online, by fax, by mail, or by calling 1-800-822-7967.

ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES RECOMMENDATION

The ACIP makes recommendations to the Centers for Disease Control and Prevention (CDC) on how FDA-approved vaccines should be incorporated into the US adult and pediatric immunization schedules.²⁸ Each ACIP recommendation is constructed using the ACIP Evidence to Recommend Framework, which considers not only vaccine efficacy and safety, but factors such as feasibility, equity, and resource use.²⁹ Based on this framework, the ACIP’s recommendations for a vaccine may differ from the FDA-approved indications.

The ACIP’s recommendations fall into 3 categories: routine, risk-based, and shared clinical decision-making (SCDM). Initially, when RSVPreF and RSVPreF3 were authorized by the FDA in the summer of 2023, the ACIP recommended adults 60 years and older be vaccinated using SCDM. In June 2024, the ACIP revised this recommendation and now recommends RSV vaccination as a routine immunization for adults 75 years and older and as a risk-based immunization for adults 60 to 74 years.³⁰

VACCINE STORAGE AND HANDLING

Some vaccines require special storage and handling. Clinicians should ensure that all staff involved in vaccine ordering, storage, handling, and administration receive appropriate training. Resources to provide training are available through the CDC, including a comprehensive web-based training course called Building Awareness of Immunization & Vaccine.

COVID-19 vaccines need to be stored in frozen or ultra-frozen conditions, limiting the ability of some vaccine providers to stock and administer them. However, most of the RSV immunizations are stored at standard refrigerator temperatures, making them more convenient to stock in the provider office. The exception is the Moderna vaccine, which is stored in a standard vaccine freezer or can be thawed and stored refrigerated for up to 30 days. Each RSV immunization is supplied in distinctive product-specific packaging, which may help vaccine providers distinguish between products.

Palivizumab is supplied in a 50-mg/0.5-mL vial and a 100-mg/1-mL vial. The dose volume must be calculated based on each patient’s weight:

Palivizumab vials are intended to be single-dose and are preservative-free. After withdrawing the calculated dose, any remaining unused suspension should be safely discarded. Vaccine providers should not “pool” partially used vials to comprise doses. Doses greater than 1 mL in volume should be given in divided doses.¹²

Nirsevimab comes in a 50-mg/0.5-mL prefilled syringe and a 100-mg/1-mL prefilled syringe; each can be purchased in single-dose or 5-dose cartons. Children indicated to receive a 200-mg dose of nirsevimab in their second RSV season should receive 2 100-mg/1-mL injections. At present, the CDC recommends against using 2 50-mg/0.5-mL syringes to make up a 100-mg dose.¹⁴

RSVpreF is supplied as a kit that contains a vial of lyophilized antigen powder, a prefilled syringe of sterile water diluent, and a vial adapter. To prepare a dose, the vial of lyophilized antigen powder is reconstituted with the prefilled syringe of sterile water diluent. Vaccine providers can purchase RSVpreF in cartons that contain 1-, 5-, or 10-dose kits.¹⁶

RSVPreF3 is supplied in a 10-dose carton that contains 10 vials of lyophilized antigen powder and 10 vials of acute disseminated encephalomyelitis adjuvant suspension. To prepare a dose, 1 vial of lyophilized antigen powder is reconstituted with 1 vial of the adjuvant suspension.²³ mRNA-1345 is supplied as a 0.5-mL prefilled syringe that is available for purchase in a single-dose-or 10-dose carton.

COST AND INSURANCE COVERAGE

It is important to be familiar with cost and insurance coverage when making recommendations for immunization to patients and their families. Before any RSV vaccines were approved, a survey of primary care physicians in the United States found that the most common anticipated barrier to RSV immunization would be insurance coverage and reimbursement.³¹ In general, public and private insurance plans are required to cover vaccines recommended in the ACIP adult and pediatric immunization schedules, including vaccines recommended with shared clinical decision-making.

An important nuance for Medicare beneficiaries is determining whether the vaccine should be given in the medical office or pharmacy setting. The COVID-19, influenza, hepatitis B, and pneumococcal vaccines are covered under Medicare Part B, meaning that they are fully covered when given in the medical office setting. Provisions from the Affordable Care Act require that these vaccines be covered in-office with no out-of-pocket expense to the patient. Other vaccines, including RSV, are covered under Medicare Part D. These vaccines are billed by the pharmacy as a prescription, so they must be administered in the pharmacy. Previously, this meant patients were subject to prescription copayments for pharmacy-based immunizations. However, the Inflation Reduction Act removed cost-sharing, so these vaccines are available to patients with a zero-dollar copay.

Adults with private insurance coverage, TriCare, or Medicaid can typically receive vaccines in the medical or pharmacy setting. While the CDC’s Bridge Access Program provides COVID-19 vaccine free of charge, programs to provide other vaccines to uninsured adults are limited.

The ACIP approved the addition of nirsevimab to the Recommended Child and Adolescent Immunization Schedule. As such, nirsevimab is covered by commercial and public insurance plans as a medical benefit with no out-of-pocket expense to the patient or their family. Nirsevimab is also provided free through the Vaccines for Children program for uninsured and underinsured children. Conversely, palivizumab is not included on the ACIP immunization schedule, nor is it provided through the Vaccines for Children Program. Instead, insurance companies require medical providers to submit for prior authorization to confirm patient eligibility for palivizumab administration.

PREVENTING IMMUNIZATION ERRORS

The Institute for Safe Medication Practices (ISMP) published a safety brief in their November 2023 newsletter advising clinicians of the risk of medication errors related to the adult and pediatric-intended RSV preventive products. Given the proximity of their release, the ISMP warned that it would be very easy for providers to mix up the product names, doses, and schedules of the RSV vaccines for adults and RSV antibodies for infants and young children.

In a January 2024 newsletter, the CDC detailed administration errors reported to the VAERS related to RSV immunizations. As of January 17, 2024, at least 25 children less than 2 years of age had erroneously received an adult RSV vaccine instead of an RSV monoclonal antibody, and 128 pregnant women had received RSVPreF3 instead of RSVpreF.

Per the CDC report, most administration errors did not result in an adverse event. Those that did occur were most often classified as nonserious, although details have not yet been published. People who experienced an administration error continue to be tracked and monitored by VAERS officials. While the exact causes of these administration errors remain unknown, resources from ISMP, CDC, and the Immunization Action Coalition provide detailed guidance on how vaccine providers can avoid the most common immunization errors. Recommended best practices are summarized in Table 2.

FUTURE DIRECTIONS

The approval of 3 new RSV immunizations in 2023 and 1 in 2024 so far marks a huge step in the advancement of RSV prevention. However, additional research is needed to expand immunization efforts to other vulnerable populations including adults less than 60 years of age with comorbid or immunocompromising conditions. The development of combined influenza, COVID-19, and RSV vaccines could also help reduce vaccine fatigue and increase vaccine uptake in the future.

Also in the pipeline is a new monoclonal antibody, clesrovimab (MK-1654; Merck); infants and children are currently being recruited for a phase 3 trial comparing this agent with palivizumab.

DISCLOSURES

Dr. DeVolld reports no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest. Dr. Rivard has disclosed serving as an advisor or review panel participant for Pfizer.