Immunogenicity and Safety of the Adjuvanted Respiratory Syncytial Virus Prefusion F Protein-Based Vaccine When Co-administered With the Adjuvanted Recombinant Herpes Zoster Subunit Vaccine in Adults ≥ 50 Years of Age

BACKGROUND: Co-administration of AS01E-adjuvanted respiratory syncytial virus vaccine (adjuvanted RSVPreF3) and AS01B-adjuvanted recombinant herpes zoster subunit vaccine (RZV), although not contraindicated, has not been previously studied in clinical trials. METHODS: This phase III, open-label, randomized (1:1) trial evaluated the immunogenicity, safety, and reactogenicity of adjuvanted RSVPreF3 when co-administered with RZV in ≥50-year-olds. The 2 vaccines were either co-administered at visit 1 (day [D] 1; Co-Ad), or were given sequentially, 1 month apart (RZV dose 1 at D1, adjuvanted RSVPreF3 at D31; Control). All participants received RZV dose-2 at D61. Non-inferiority of humoral immune responses was demonstrated if 95% confidence interval (CI) upper limits for geometric mean RSV-A/B neutralizing titers (GMT) and varicella-zoster virus anti-glycoprotein E (anti-gE) antibody concentration (GMC) ratios (Control/Co-Ad) were ≤1.5. Safety and reactogenicity were secondary endpoints. RESULTS: Overall, 530 participants (Co-Ad = 265; Control = 265) were vaccinated. Neutralizing GMT ratios for RSV-A (1.1 [95% CI = 1.0-1.4]) and RSV-B (1.0 [0.8-1.2]), and anti-gE antibody GMC ratio (1.2 [1.1-1.4]) met non-inferiority criteria. Within 7 days post-vaccination, 71.7% (Co-Ad: post-RZV dose 1 and adjuvanted RSVPreF3; grade [Gr] 3 = 3.9%), 58.5% (Control: post-RZV dose 1; Gr3 = 1.9%), and 47.8% (Control: post-adjuvanted RSVPreF3; Gr3 = 1.2%) of participants reported solicited administration-site adverse events (AEs). Post-visit 1, 73.6% (Gr3 = 9.3%) of Co-Ad and 60.4% (Gr3 = 6.2%) of control participants reported solicited systemic AEs. Within 30 days post-any vaccination, 23.4% (Gr3 = 0.8%) of Co-Ad and 30.2% (Gr3 = 1.1%) of control participants reported unsolicited AEs. No fatal or related serious AEs were reported. CONCLUSIONS: Immunogenicity, reactogenicity, and safety data support the co-administration of adjuvanted RSVPreF3 and RZV. CLINICAL TRIALS REGISTRATION: NCT05966090.