Trivalent Adjuvanted, High-Dose Inactivated Influenza Vaccines Safe for Older Adults

Healthcare professional in protective gloves & workwear holding & organising a tray of COVID-19 vaccine vials. The professional is carrying out researches on COVID-19 vaccine in laboratory.
Researchers compared safety, reactogenicity, and changes in Health-Related Quality of Life scores of aIIV3 vs HD-IIV3 flu vaccines in older adults.

Both the trivalent adjuvanted inactivated influenza vaccine (aIIV3) and high-dose inactivated influenza vaccine (HD-IIV3) were safe to administer to adults aged 65 years and older. These findings from a safety and reactogenicity study were published in JAMA Network Open.

Adults (N=757) aged 65 years and older were recruited at Duke University Medical Center, Boston Medical Center, and Cincinnati Children’s Hospital Medical Center during the 2017 to 2018 and 2018 to 2019 influenza seasons. Participants were randomly assigned in a 1:1 ratio to receive either of the 0.5 mL egg-based vaccines intramuscularly. The aIIV3 and HD-IIV3 vaccines contained 15 and 60 mg from each of the 3 influenza strains for each season, respectively. Research staff evaluated participants for adverse events after vaccination for 15 minutes and reactogenicity and unsolicited adverse events from vaccination day through day 8.

The median age of vaccine recipients was 72 years (range, 65-97), 55% were women, and 78% were White. The vaccine was administered from 2017 to 2018 (n=279) and 2018 to 2019 (n=478).

Moderate to severe injection site pain was reported by 3.2% of the aIIV3 and 5.8% of the HD-IIV3 recipients (difference, -2.7%; 95% CI, -5.8 to 0.4). Severe local reactions were reported by 3.7% of aIIV3 and 2.9% of HD-IIV3 recipients and severe systemic reactions by 4.8% of aIIV3 and 4.0% of HD-IIV3 recipients. No participant sought medical attention during the first week after vaccination.

Severe adverse events were observed among 2.4% (95% CI, 1.1-4.5) and 0.8% (95% CI, 0.2-2.2) of the aIIV3 and HD-IIV3 vaccine recipients, respectively.

The participants were assessed for Health-Related Quality of Life before and after vaccination. Compared with baseline, at day 3, the aIIV3 and HD-IIV3 recipients reported a change of -0.05 and -0.05 in their EuroQoL 5 Dimensions-5 Level scores and -2.22 and -2.49 for their EQ-Visual Analogue Scale, respectively.

Participants aged 65 to 79 years indicated a greater decrease in Late-Life Function and Disability Instrument social roles scores among the HD-IIV3 recipients (-1.98) compared with aIIV3 (-0.66; P =.04) at 3 days.

This study may have been limited by recruiting community-dwelling adults who were highly educated and with high self-rated health. It remains unclear whether similar results would be observed among a more infirm population.

These findings indicated that both the aIIV3 and HD-IIV3 influenza vaccines were safe for use among older adults.

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Schmader KE, Liu CK, Harrington T, et al. Safety, reactogenicity, and health-related quality of life after trivalent adjuvanted vs trivalent high-dose inactivated influenza vaccines in older adults: a randomized clinical trial. JAMA Netw Open. 2021;4(1):e2031266. doi:10.1001/jamanetworkopen.2020.31266