Safety of Simultaneous Vaccination With Adjuvanted Zoster Vaccine and Adjuvanted Influenza Vaccine: A Randomized Clinical Trial.

Abstract

Quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) and adjuvanted recombinant zoster vaccine (RZV) contain novel adjuvants. Data are limited on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of the simultaneous administration of these vaccines. To compare the safety and reactogenicity after simultaneous doses of RZV and aIIV4 administration (opposite arms) with simultaneous doses of RZV with quadrivalent high-dose inactivated influenza vaccine [HD-IIV4]). This randomized blinded clinical trial was conducted during the 2021-2022 and 2022-2023 influenza seasons at 2 centers in the US among community-dwelling adults aged 65 years or older. Analysis was performed on an intention-to-treat basis. Simultaneous intramuscular administration of RZV dose 1 and aIIV4 or HD-IIV4 in opposite arms after age stratification (65-69 and ≥70 years) and randomization. The primary outcome was the proportions of participants with 1 or more severe solicited reactions during days 1 to 8, using a noninferiority test (10% noninferiority margin). Additional measures included serious adverse events and adverse events of clinical interest during days 1 to 43 of the study period. A total of 267 adults (median age, 71 years [range, 65-92 years]; 137 men [51.3%]) were randomized; 130 received simultaneous RZV and aIIV4, and 137 received simultaneous RZV and HD-IIV4. The proportion of patients reporting 1 or more severe reactions after simultaneous administration of RZV and aIIV4 (15 of 115 [11.5%]) was noninferior compared with simultaneous RZV and HD-IIV4 (17 of 119 [12.5%]) (absolute difference, -1.0% [95% CI, -8.9% to 7.1%]). There were no significant differences in the number of serious adverse events or adverse events of clinical interest between the groups. In this clinical trial of simultaneous doses of RZV and aIIV4 compared with simultaneous doses of RZV and HD-IIV4, overall safety findings were similar between groups. From a safety standpoint, this study supports the simultaneous administration of RZV and aIIV4 among older adults. ClinicalTrials.gov Identifier: NCT05007041.