Comparative Analysis of Recombinant Quadrivalent Influenza Vaccine and Standard Egg-Based Quadrivalent Influenza Vaccine in Nursing Home Residents: A Cluster Randomized Trial

Academic Background

Influenza is among the primary respiratory pathogens causing morbidity and mortality among the elderly worldwide, particularly in nursing home residents who are at heightened risk of infection. Influenza vaccination is the most important intervention to prevent influenza-related diseases and deaths. However, vaccine efficacy varies by season and vaccine type. Recently, the recombinant influenza vaccine (RIV4) has garnered attention for its higher antigen dosage and stronger immune response. While studies have demonstrated the superior efficacy of RIV4 compared to standard-dose egg-based influenza vaccines (IIV4) in outpatient older adults, its effectiveness in nursing home residents has not been fully evaluated.

This study aims to compare hospitalization rates among nursing home residents vaccinated with the recombinant quadrivalent influenza vaccine (RIV4) versus those vaccinated with the standard egg-based quadrivalent influenza vaccine (IIV4). The study’s primary endpoint is the rate of respiratory-related hospitalizations, and secondary endpoints include all-cause hospitalization rates and mortality rates.

Paper Source

This paper was authored by Kevin W. McConeghy et al. The authors are affiliated with multiple institutions, including the Brown University School of Public Health, the Veterans Affairs Providence Health Care System, and University Hospitals Cleveland Medical Center. The paper was published on January 2, 2025, in the JAMA Network Open journal, DOI: 10.1001/jamanetworkopen.2024.52677.

Study Design and Methods

Research Design and Participants

This study is a pragmatic cluster randomized trial. Participants were U.S. nursing home residents aged 65 years or older who had resided at the nursing homes for at least 100 consecutive days before the beginning of influenza season. The study spanned the 2019-2020 and 2020-2021 influenza seasons. Nursing homes were stratified by the proportion of Black residents and prior hospitalization rates, then randomly assigned 1:1 to either the RIV4 or IIV4 group. Medicare claims data were used to evaluate resident-level hospitalization outcomes.

Intervention

Nursing homes were randomized to administer either RIV4 or IIV4 to all residents. Vaccines were directly shipped to the facilities, which followed the vaccination guidelines provided by the U.S. Centers for Disease Control and Prevention (CDC). Most nursing homes vaccinated residents over 1–2 days in late September to early October.

Data Sources and Statistical Analysis

The study relied on Medicare claims data, the Minimum Data Set (MDS), and hospitalization records to define cohorts, describe baseline characteristics, and measure outcomes. The primary endpoint was respiratory-related hospitalization rates, while secondary endpoints included all-cause hospitalization and mortality rates. Statistical analysis included Cox proportional hazards regression models to estimate hazard ratios (HRs) between groups, and subgroup analyses were conducted.

Study Results

Participants

The study included 144,565 person-observations (mean age: 77.4 years, 63.0% female) from 1,078 nursing homes. Of these, 72,005 residents were assigned to the RIV4 group, and 72,560 were assigned to the IIV4 group. A total of 85.6% of residents received influenza vaccination, and baseline characteristics between the two groups were comparable.

Primary Results

For the primary endpoint, respiratory-related hospitalizations occurred in 1,387 cases (1.9%) in the RIV4 group and 1,424 cases (2.0%) in the IIV4 group (HR: 1.01; 95% CI, 0.62–2.17). Pneumonia and influenza-related hospitalizations were also similar between the RIV4 group (0.8%) and the IIV4 group (0.8%) (HR: 0.98; 95% CI, 0.41–2.47). Rates of all-cause hospitalizations and mortality did not differ significantly between the groups.

Subgroup Analysis

Subgroup analyses showed no significant differences in hospitalization rates between the two groups across variables such as gender, race, age, and underlying conditions. Although some subgroups (e.g., residents with chronic kidney disease or hip fractures) showed HRs favoring RIV4, these differences were not statistically significant.

Discussion and Conclusion

Discussion

The study found no evidence that RIV4 was superior to IIV4 in reducing respiratory-related hospitalizations, all-cause hospitalizations, or mortality rates among nursing home residents. These findings are inconsistent with previous studies, likely due to different study populations (nursing home residents are typically older, frail, and less responsive to vaccines) or due to seasonal and antigenic variations. Additionally, the ongoing COVID-19 pandemic significantly reduced influenza activity during the study period, affecting assessments of vaccine efficacy.

Conclusion

This cluster randomized trial did not find significant differences between recombinant and standard egg-based influenza vaccines in terms of hospitalization and mortality rates in elderly nursing home residents during the 2019-2020 and 2020-2021 influenza seasons. However, the COVID-19 pandemic and poor vaccine-virus match limited the generalizability of the findings. Based on the current evidence, RIV4 remains a reasonable first-line choice, but this study does not indicate its superiority in the nursing home population.

Study Highlights

1. Unique Study Population: The study focuses on nursing home residents, a population at high risk of influenza and an often underrepresented group in vaccine efficacy trials.
2. Large-Scale Randomization: Spanning two influenza seasons and including over 144,000 observations, this trial provides robust evidence.
3. Pragmatic Design: The cluster-randomized design mirrors real-world vaccine administration practices and enhances the study’s generalizability.
4. Impact of COVID-19: The pandemic significantly influenced influenza activity, highlighting the complexities of studying influenza vaccine efficacy during concurrent public health crises.

Study Impact

This study provides critical evidence for vaccine selection in nursing home residents. Despite finding no superiority of RIV4, its non-inferiority supports its recommendation as a first-line option for this population. The findings also underscore the importance of accounting for seasonal variations and antigenic matching in influenza vaccine research, offering valuable insights for future studies and policy-making.