A Randomized Phase 1 Clinical Trial of a Respiratory Syncytial Virus and Human Metapneumovirus Combination Protein-Based Virus-like Particle Vaccine in Adults 60-75 Years of Age.

Background: Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are important causes of severe lower respiratory tract disease (LRTD) in adults ≥65 years of age. We report safety and immunogenicity for IVX-A12, a combination, protein-based virus-like particle (VLP) vaccine against RSV- and hMPV-associated LRTD. Methods: This phase 1 trial (NCT05664334) randomized healthy adults 60-75 years of age to receive 1 intramuscular dose of IVX-A12 at low (75 µg RSV/75 µg hMPV), medium (75 µg RSV/150 µg hMPV), or high dose levels (75 µg RSV/225 µg hMPV) ± oil-in-water adjuvant MF59® (low and medium dose levels only), or placebo. Safety and immunogenicity were assessed through day 365 postvaccination. Results: Overall, 140 participants received IVX-A12 (n = 117) or placebo (n = 23). Solicited adverse reactions (ARs) were transient, with mild to moderate severity; ARs were reported by 47.0% (n = 55/117) and 34.8% (n = 8/23) of IVX-A12 and placebo recipients, respectively. There were no vaccine-related serious adverse events. All IVX-A12 dose levels and formulations boosted preexisting RSV- and hMPV-specific neutralizing antibody (nAb) responses; from baseline to day 28, nAb titers against RSV A or B increased up to 4- or 3-fold, and nAb titers against hMPV A or B increased up to 5- or 4-fold, respectively. Neutralizing responses in IVX-A12 recipients through day 365 were maintained above or around baseline and exceeded those in placebo recipients. Conclusions: IVX-A12 was well-tolerated and elicited RSV- and hMPV-specific antibody responses in adults 60-75 years of age. These data support the ongoing clinical development of the RSV/hMPV combination VLP vaccine IVX-A12.