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

Abstract

Importance: 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.

Objective: 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]).

Design, setting, and participants: 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.

Intervention: 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.

Main outcomes and measures: 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.

Results: 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.

Conclusions and relevance: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT05007041.

Figure 1.. CONSORT Diagram

Randomization and patient flow in the study comparing recombinant zoster vaccine dose 1 and quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) vs recombinant zoster vaccine dose 1 and quadrivalent high-dose inactivated influenza vaccine (HD-IIV4). The intention-to-treat (ITT) population consisted of all participants who were randomized and vaccinated. The modified ITT (mITT) population consisted of all participants who were randomized, vaccinated, and provided at least 1 day of complete data on the symptom diary form.

Figure 2.. Difference in Proportions for Any Severe, Local, or Systemic Reactions From Recombinant Zoster Vaccine (RZV) Dose 1 and Quadrivalent Adjuvanted Inactivated Influenza Vaccine (aIIV4) vs RZV Dose 1 and Quadrivalent High-Dose Inactivated Influenza Vaccine (HD-IIV4)

Mean differences and 95% CIs in proportions of severe (grade 3) reactions (any, local, or systemic) after RZV dose 1 and aIIV4 minus RZV dose 1 and HD-IIV4 are shown. The vertical dotted line at 0 indicates no difference, and the vertical dotted line at 10 indicates the 10% noninferiority margin. Error bars indicate 95% CIs.