Immunogenicity and safety of co-administration of a recombinant shingles vaccine with an mRNA COVID-19 or adjuvanted influenza vaccine: a randomised controlled trial

BACKGROUND: Coverage of the recombinant herpes zoster vaccine (RZV) could be improved by coadministration with seasonal vaccines. We evaluated the immunogenicity and safety of co-administration of the first or second dose of RZV with an adjuvanted quadrivalent influenza vaccine (aQIV), or mRNA COVID-19 vaccine. METHODS: A multicentre, randomised, controlled, non-inferiority phase 4 trial with masking, across 13 sites. Healthy adults ≥50 years were randomised (1:1:2:2:2) to one of five groups. Co-primary immunogenicity outcomes were evaluated one month after the relevant vaccine: RZV by anti-gE Ig; COVID-19 by anti-S Ig; and aQIV by haemagglutinin antibody inhibition titres. The co-primary safety outcome was grade 3/4 solicited systemic reaction(s) in the seven days after vaccination. RESULTS: Between 15/10/2023 and 27/02/2025 967 participants were recruited (median age 60.5 years, 55% female). Non-inferiority was indicated for all coprimary immunogenicity outcomes, i.e. the lower limit of 95% confidence intervals exceeded the pre-specified non-inferiority criteria (geometric mean ratio=0.67). Rates of the primary safety outcome were low, albeit slightly increased with co-administration; maximum 3.3% for co-administration of RZV/COVID-19, minimum 1.2% for COVID-19 alone. CONCLUSIONS: COVID-19 vaccine and aQIV can be safely co-administered with both doses of RZV without impacting the immunogenicity of any of the vaccines.