Which Enhanced Influenza Vaccine Has the Greatest Immunogenicity in Long-Term Care Residents: The Adjuvanted or the High-Dose Formulation?

Objectives

This study compares enhanced influenza vaccines recommended for older adults, adjuvanted flu vaccine (aTIV, FLUAD) vs high-dose flu vaccine (HD-IIV3, FLUZONE HD) to determine if they met noninferiority standards for older long-term care facility (LTCF) residents.

Design

A phase 4, randomized, active-controlled, noninferiority trial on influenza vaccine immunogenicity conducted over 2 influenza seasons (2018-2019 and 2019-2020) (NCT03694808).

Setting and Participants

Residents of LTCFs aged ≥65 years.

Methods

Participants were randomized 1:1 to receive either aTIV or HD-IIV3 using computer-generated randomization. Only laboratory personnel were blinded. Hemagglutination inhibition (HAI) and neuraminidase inhibition (NI) assays measured antibody responses at baseline and 28 days postvaccination. The primary outcome compared the geometric mean titers (GMTs) at day 28. Secondary outcomes included seroconversion rates and NI titers.

Results

We randomized 387 LTCF residents to receive either aTIV (n = 194) or HD-IIV3 (n = 193) over 2 flu seasons. We observed noninferior HAI levels at postvaccination day 28 to A/H1N1 and A/H3N2 for aTIV and HD-IIV3 (GMT ratio, 1.03; 95% CI, 0.76-1.4; and GMT ratio, 1.04; 95% CI, 0.73-1.48, respectively), meeting noninferiority criteria with 95% CI upper bounds <1.5. However, noninferiority criteria were not met for influenza B HAI levels (GMT ratio, 1.21; 95% CI, 0.91-1.61). Also, noninferiority criteria for HAI seroconversion were not met for any of the 3 strains. Applying the same noninferiority criteria to NI, both day 28 titer and seroconversion in aTIV were noninferior to HD-IIV3 for A/H1N1 and A/H3N2 strains.

Conclusions and Implications

Overall the anti-hemagglutinin and anti-neuraminidase titers demonstrate similarities between the vaccines and support them both being in the enhanced flu vaccine category preferentially recommended by the Centers for Disease Control and Prevention for people aged ≥65 years.