RSV Vaccine Safety in the Elderly
RSV vaccines are generally safe for elderly adults, with common mild-to-moderate injection site reactions and systemic symptoms, but postlicensure surveillance has identified a potential increased risk of Guillain-Barré syndrome (GBS) with protein subunit vaccines (Arexvy and Abrysvo), which must be weighed against substantial benefits in preventing severe disease, hospitalization, and death. 1
Safety Profile Overview
Common Adverse Events
The most frequently reported adverse events are mild to moderate and include: 2, 3, 4
- Injection site pain (most common)
- Fatigue
- Myalgia (muscle pain)
- Headache
- Arthralgia (joint pain)
Meta-analysis of 14 studies involving 76,695 participants demonstrated higher overall adverse events in vaccinated groups compared to placebo, primarily driven by injection-site reactions and vaccine-related symptoms. 2 However, these reactions are typically self-limited and resolve within days.
Serious Adverse Events
No significant difference in serious adverse events was observed between vaccinated and placebo groups in pooled analyses. 2 This is reassuring for the general elderly population, including those with multiple comorbidities.
Critical Safety Signal: Guillain-Barré Syndrome
The most important safety concern identified through postlicensure surveillance is a potential increased risk of GBS following protein subunit RSV vaccination (specifically GSK's Arexvy and Pfizer's Abrysvo). 1 This finding led to important changes in ACIP recommendations:
- The FDA has required warnings about GBS risk in the prescribing information for Arexvy and Abrysvo 5
- For adults aged 60-74 years without risk factors, ACIP concluded that benefits did not clearly outweigh potential harms, leading to a risk-based rather than universal recommendation 1
- No GBS signal was observed with Moderna's mRNA-based vaccine (mRESVIA) in clinical trials, though postlicensure surveillance data are still pending 1
Risk-Benefit Analysis
Despite the GBS concern, estimated RSV-associated hospitalizations, ICU admissions, and deaths preventable over two RSV seasons per 1 million vaccine doses administered exceed estimated numbers of potential vaccine-attributable GBS cases. 6 This favorable risk-benefit ratio supports vaccination in high-risk populations.
Safety in Special Populations
Immunocompromised Patients
All approved RSV vaccines are non-live, recombinant subunit or mRNA formulations that cannot replicate in the human body, making them safe for immunocompromised patients. 7 This includes:
- Cancer patients on chemotherapy
- Solid organ transplant recipients
- Patients on immunosuppressive medications
- HIV-positive individuals
No special precautions regarding live vaccine administration apply. 7
Patients with Multiple Comorbidities
The vaccines have been studied and are recommended for elderly patients with: 1, 8
- Chronic cardiovascular disease (heart failure, coronary artery disease)
- Chronic lung disease (COPD, asthma, interstitial lung disease)
- End-stage renal disease
- Diabetes with complications
- Chronic liver disease (cirrhosis)
- Severe obesity (BMI ≥40 kg/m²)
- Neurologic conditions affecting airway clearance
These comorbid conditions increase the risk of severe RSV disease substantially more than they increase vaccine-related risks. 1, 8
Frail Elderly and Nursing Home Residents
Frailty and nursing home residence are recognized risk factors for severe RSV disease. 1, 8 The vaccines are safe in these populations, and all adults aged ≥75 years should receive vaccination regardless of health status or frailty. 7, 6
Clinical Algorithm for Safe Vaccination
Step 1: Age-Based Assessment
- Age ≥75 years: Vaccinate universally—benefits clearly outweigh risks 7, 6
- Age 60-74 years: Proceed to risk factor assessment 1
- Age 50-59 years: Only RSVPreF3 (Arexvy) is approved; requires risk factors 7, 8
Step 2: Risk Factor Identification (for ages 60-74)
Patient attestation alone is sufficient—do not delay vaccination for medical documentation. 1, 6 Screen for:
- Chronic cardiopulmonary disease
- Metabolic conditions (diabetes, chronic kidney disease)
- Immunocompromise
- Nursing home residence
- Severe obesity or frailty 1
Step 3: Vaccine Selection Considerations
- For immunocompromised patients: All three vaccines are safe options 7
- If GBS history: Exercise caution with protein subunit vaccines; consider mRNA option when available 5
- For ages 50-59: Only Arexvy is approved 7
Step 4: Administration
- Single lifetime dose only 7, 6
- Can co-administer with influenza vaccine at different sites 7, 6
- Preferably September-November before RSV season 7, 6
Important Caveats and Pitfalls
Do Not Deny Vaccination Due To:
- Lack of medical documentation—patient attestation is sufficient 1, 6
- Previous RSV infection—does not confer lasting immunity or contraindicate vaccination 7, 8
- Immunocompromised status—vaccines are non-live and safe 7
- Multiple comorbidities—these patients benefit most 1, 8
Do Not Administer:
- Multiple doses—only one lifetime dose is recommended 7, 6
- To patients who already received any RSV vaccine—no revaccination indicated 6
Monitor For:
- GBS symptoms in the 42 days post-vaccination (weakness, tingling, difficulty walking) 5
- This risk must be communicated but should not prevent vaccination in high-risk individuals where benefits are substantial 1
Tolerability Across Vaccine Types
All three approved vaccines (Arexvy, Abrysvo, and mRESVIA) demonstrate similar safety profiles with mild-to-moderate local and systemic reactions. 3, 5 The vaccines were generally well tolerated in clinical trials involving older adults, including those with underlying conditions. 3, 4
The key distinction is the GBS signal observed with protein subunit vaccines but not yet with the mRNA vaccine in pre-licensure trials. 1, 5 However, real-world postlicensure surveillance for mRESVIA is still needed.