No Immunological Interference or Safety Concerns When Adjuvanted Recombinant Zoster Vaccine Is Coadministered With a Coronavirus Disease 2019 mRNA-1273 Booster Vaccine in Adults Aged 50 Years and Older: A Randomized Trial

Abstract

Background: There is growing consensus that coronavirus disease 2019 booster vaccines may be coadministered with other age-appropriate vaccines. Adding to the limited available data supporting coadministration, especially with adjuvanted vaccines, could enhance vaccine coverage in adults.

Methods: In this phase 3, randomized, open-label study, eligible adults aged ≥50 years were randomly assigned (1:1) to receive mRNA-1273 (50 µg) booster vaccination and a first dose of recombinant zoster vaccine (RZV1) 2 weeks apart (Seq group) or concomitantly (Coad group). The second RZV dose (RZV2) was administered 2 months post-RZV1 in both groups. Primary objectives were noninferiority of anti-glycoprotein E (gE) and anti-spike protein antibody responses in the Coad group compared to the Seq group. Safety and further immunogenicity assessments were secondary objectives.

Results: In total, 273 participants were randomized to the Seq group and 272 to the Coad group. Protocol-specified noninferiority criteria were met. The adjusted geometric mean concentration ratio (Seq/Coad) was 1.01 (95% confidence interval [CI], .89-1.13) for anti-gE antibodies 1 month post-RZV2, and 1.09 (95% CI, .90-1.32) for anti-spike antibodies 1 month post-mRNA-1273 booster. No clinically relevant differences were observed in overall frequency, intensity, or duration of adverse events between the 2 study groups. Most solicited adverse events were mild/moderate in intensity, each with median duration ≤2.5 days. Administration site pain and myalgia were the most frequently reported in both groups.

Conclusions: Coadministration of mRNA-1273 booster vaccine with RZV in adults aged ≥50 years was immunologically noninferior to sequential administration and had a safety and reactogenicity profile consistent with both vaccines administered sequentially. Clinical Trials Registration. NCT05047770.

Keywords: coadministration; immunogenicity; mRNA COVID-19 vaccine; recombinant zoster vaccine; safety.

Graphical Abstract

Figure 1.

Participant flow. The Seq group received the mRNA-1273 booster dose followed 2 weeks later by the first dose of RZV. The Coad group received coadministration of the mRNA-1273 booster and the first dose of RZV. Abbreviations: D, study day; LTFU, lost to follow-up; mRNA-1273, Moderna's messenger RNA COVID-19 vaccine; PPS, per-protocol set; RZV, recombinant zoster vaccine.

Figure 2.

Percentage of solicited local and systemic adverse events reported per participant after the mRNA-1273 and first RZV vaccinations (exposed set). The Seq group received the mRNA-1273 booster dose followed 2 weeks later by the first dose of RZV. The Coad group received coadministration of the mRNA-1273 booster and the first dose of RZV. Definitions of grade 3 intensity are provided in the Supplementary Material. Abbreviations: AE, adverse event; GI, gastrointestinal; mRNA-1273, Moderna's messenger RNA COVID-19 vaccine; RZV, recombinant zoster vaccine.