Shapiro Craig, Sánchez-Crespo Nelia, Ciarlet Max, Hourguettes Nicholas, Wen Judy, Rida Wasima, Price Jennifer, Engram April E, Adams Elizabeth M, Kanesa-Thasan Niranjan
Cenexel RCA, Hollywood, Florida, USA.
Icosavax, Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Seattle, Washington, USA.
Open Forum Infect Dis. 2025 Mar 13;12(4):ofaf160. doi: 10.1093/ofid/ofaf160. eCollection 2025 Apr.
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.
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.
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.
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.
呼吸道合胞病毒（RSV）和人偏肺病毒（hMPV）是65岁及以上成年人严重下呼吸道疾病（LRTD）的重要病因。我们报告了IVX-A12的安全性和免疫原性，IVX-A12是一种基于蛋白质的联合病毒样颗粒（VLP）疫苗，用于预防与RSV和hMPV相关的LRTD。
这项1期试验（NCT05664334）将60-75岁的健康成年人随机分组，分别接受1剂肌肉注射的低剂量（75μg RSV/75μg hMPV）、中剂量（75μg RSV/150μg hMPV）或高剂量（75μg RSV/225μg hMPV）的IVX-A12，±水包油佐剂MF59®（仅低剂量和中剂量组），或安慰剂。在接种疫苗后365天内评估安全性和免疫原性。
总体而言，140名参与者接受了IVX-A12（n = 117）或安慰剂（n = 23）。主动报告的不良反应（ARs）是短暂的，严重程度为轻至中度；IVX-A12组和安慰剂组分别有47.0%（n = 55/117）和34.8%（n = 8/23）的参与者报告了ARs。没有与疫苗相关的严重不良事件。所有IVX-A12剂量水平和配方均增强了预先存在的RSV和hMPV特异性中和抗体（nAb）反应；从基线到第28天，针对RSV A或B的nAb滴度分别提高了4倍或3倍，针对hMPV A或B的nAb滴度分别提高了5倍或四倍。IVX-A12接种者在365天内的中和反应维持在基线以上或基线左右，并超过了安慰剂接种者。
IVX-A12耐受性良好，并在60-75岁的成年人中引发了RSV和hMPV特异性抗体反应。这些数据支持RSV/hMPV联合VLP疫苗IVX-A12正在进行的临床开发。
