Efficacy of Influenza Vaccine in the Elderly
Influenza vaccination in elderly adults (≥65 years) demonstrates substantial efficacy with a 48% reduction in mortality risk and 27% reduction in hospitalization risk, and high-dose or adjuvanted formulations should be preferentially used in this population to optimize protection against influenza-related morbidity and mortality. 1
Overall Vaccine Efficacy in Elderly Adults
The WHO reports that influenza vaccination offers approximately 70% protection in healthy adults, though efficacy is reduced in elderly populations due to immunosenescence 1. Despite diminished immune responses with aging, vaccination remains the primary preventive strategy and is considered a critical component of healthy aging 1.
Key efficacy outcomes in community-dwelling adults ≥65 years include: 1
- 48% reduction in mortality risk
- 27% reduction in hospitalization risk
- Lower rates of ICU admission, invasive ventilation, and bacterial pneumonia among vaccinated hospitalized patients
- Cost reduction of 2.75% and reduction in years of life lost by over 50%
Enhanced Vaccine Formulations: Superior Protection
High-dose and adjuvanted influenza vaccines consistently outperform standard-dose vaccines in elderly adults and should be preferentially recommended. 1, 2
High-Dose Vaccine Efficacy
High-dose quadrivalent influenza vaccine (HD-QIV) contains higher hemagglutinin content and demonstrates superior outcomes: 1
- Nursing home residents (≥65 years): Reduced respiratory-related hospital admissions (3.4% vs. 3.9% over 6 months) and lower mortality (17.1% vs. 18.3%) compared to standard-dose vaccine 1
- Immunogenicity: 1.76-2.65 fold higher geometric mean titers across all four influenza strains compared to standard-dose vaccine 3
- Real-world effectiveness: Recent 2024/25 Danish data shows overall vaccine effectiveness of 48% for adjuvanted QIV versus 33% for standard-dose QIV 4
Adjuvanted Vaccine Performance
MF59-adjuvanted vaccines demonstrate significant absolute and relative vaccine effectiveness: 5
- Absolute VE: 40.7% (95% CI: 21.9-54.9) for non-emergency outpatient visits and 58.5% (95% CI: 40.7-70.9) for hospitalized patients 5
- Relative VE: 13.9% improvement compared to standard TIV and 13.7% improvement compared to standard QIV 5
- Comparable effectiveness to high-dose vaccines in head-to-head comparisons 4, 5
Critical Context: Immunosenescence and Vaccine Response
Approximately 90% of influenza-related deaths occur in elderly adults, making vaccination essential despite reduced immune responses. 1
Age-related factors affecting vaccine efficacy include: 1
- Immunosenescence (declining immune function with age)
- Physiological changes
- Chronic comorbidities
- Prior vaccination history (repeated vaccination with standard-dose vaccine may reduce immunogenicity, particularly against A(H3N2) strains) 6
Important Caveat: Prior Vaccination Effects
Among older adults with prior-year standard-dose vaccination, antibody responses to unchanged vaccine strains are reduced by approximately one-half to four-fifths 6. However, enhanced vaccines (high-dose or adjuvanted) still induce 1.43-2.39 fold higher geometric mean titers compared to standard-dose vaccine in previously vaccinated individuals 6.
Guideline-Based Recommendations
The Advisory Committee on Immunization Practices (ACIP) recommends preferential use of higher-dose or adjuvanted influenza vaccines for all adults ≥65 years. 2
Specific formulations approved for elderly adults: 2
- Fluzone High-Dose (HD-IIV4) - licensed specifically for adults ≥65 years
- MF59-adjuvanted quadrivalent influenza vaccine (aQIV)
- Both formulations are appropriate first-line choices
For adults <65 years: Standard-dose influenza vaccines are recommended unless specific immunocompromising conditions exist (transplant recipients, those on immunosuppressive medications) 2
Practical Implementation
Do not delay vaccination if only standard-dose vaccine is available - any influenza vaccine is superior to no vaccination 2. However, when both options are available, enhanced formulations should be prioritized for all adults ≥65 years regardless of frailty status, comorbidities, or prior vaccination history 1.
The evidence supporting enhanced vaccines is consistent across multiple trials, methodologies, and real-world effectiveness studies, with benefits extending beyond institutionalized residents to community-dwelling elderly adults 1.