Safety, immunogenicity, and dose ranging of a bivalent respiratory syncytial virus and human metapneumovirus glycoprotein F-molecular clamp vaccine candidate in older adults: 1-month interim analysis of an ongoing randomised, observer-blind, placebo- and active-controlled, phase 1 trial.

Abstract

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are important causes of acute respiratory tract disease in older adults. Multipathogen vaccines in ready-to-use liquid formulations are needed. VXB-241 is a recombinant RSV-hMPV unadjuvanted fully liquid vaccine candidate. This ongoing first-in-human randomised, placebo- and RSV vaccine active-controlled, observer-blind, dose-ranging trial is being conducted in older adults aged 60-83 years preceded by a few sentinel younger adults aged 18-40 years. On day 1, older adults were randomised to receive one of six intramuscular treatments: VXB-241 at 60 μg (30 μg RSV preF +30 μg hMPV preF), 120 μg (60 + 60), 240 μg (120 + 120), or 480 μg (240 + 240), the licensed AS01_E-adjuvanted RSV vaccine (Arexvy™/RSVPreF3, GSK), or placebo. We report 1-month interim safety and immunogenicity results. A total of 270 older adults were screened; 128 were randomised and completed the month-1 visit. Solicited adverse events occurred in 23.8% of placebo, 76.2% of RSVPreF3, and 35.0%-59.1% of VXB-241 recipients, with no dose-response effect among VXB-241 recipients, except at the highest dose level. Most reactions were mild and transient. Most unsolicited adverse events were unrelated to treatment. No safety signal was detected. At month 1, RSV-A, RSV-B, hMPV-A and hMPV-B neutralising antibody titres were higher than placebo in all active treatment arms. At the 240 μg VXB-241 dose level, geometric mean fold increases were 15.06 for RSV-A and 8.07 for RSV-B versus 10.81 for RSV-A and 4.91 for RSV-B after RSVPreF3 injection, and 7.50 for hMPV-A and 6.56 for hMPV-B, with negligible increases after RSVPreF3 injection. VXB-241 showed a clinically acceptable safety and reactogenicity profile and elicited strong neutralising immune responses against RSV and hMPV in older adults. Neutralising immune responses against RSV-A and RSV-B by VXB-241 were at least as good as those obtained with the licensed adjuvanted RSVPreF3 active control.