Gonzalez-Bocco Isabel H, Frierson Rayven, Cho Alyssa, Reyes Curcio Fabiola A, Franceschi Andres E, Lahoud Chloe, Moshovitis Dimitrios G, Beluch Katherine, Balusu Manu, Keleher C Elizabeth, Sullivan Keri M, Dougan Michael, Wang Qianwen, Han Jennifer H, Nader Ahmed, Aylott Alicia, Wang Wei, Chan Brian T, Hammond Sarah P, Manne-Goehler Jennifer, Koo Sophia
Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA.
Division of Infectious Disease, Dana-Farber Cancer Institute, Boston, MA, USA.
New Microbes New Infect. 2025 Aug 8;67:101620. doi: 10.1016/j.nmni.2025.101620. eCollection 2025 Oct.
Immunocompromised individuals have a limited humoral immune response to SARS-CoV-2 vaccination and are at higher risk of severe COVID-19. Sotrovimab is a monoclonal antibody (mAb) targeting a conserved SARS-CoV-2 spike protein epitope.
This phase II open-label study evaluated the safety and tolerability of sotrovimab pre-exposure prophylaxis in immunocompromised adults with impaired vaccine response. Between February and June 2022 in the northeastern region of the USA, participants received sotrovimab 500 mg IV on Treatment Day (TD) 1 and 2000 mg IV on TD2 due to the spread of the Omicron BA.2 subvariant. Follow-up lasted 36 weeks (∼5 half-lives), assessing safety and tolerability, PK, COVID-19 incidence and severity, and quality of life.
Ninety-three subjects received 500 mg on TD1, of whom 81 received 2000 mg on TD2. Three patients reported five drug-related adverse events, four grade 2 infusion-related reactions and one grade 2 headache, all resolving quickly. Among 35 SARS-CoV-2 cases, 94 % had no activity limitations or hospitalizations per the National Institute of Allergy and Infectious Diseases Ordinal Scale. Sotrovimab exhibited dose-dependent increases in exposures at doses of 500 mg and 2000 mg.
Sotrovimab pre-exposure prophylaxis had a favorable safety profile and was well tolerated at both doses, with low immunogenicity. These findings support mAbs' safety as COVID-19 pre-exposure prophylaxis in this population.
免疫功能低下的个体对SARS-CoV-2疫苗的体液免疫反应有限，且患重症COVID-19的风险更高。索托维单抗是一种靶向保守的SARS-CoV-2刺突蛋白表位的单克隆抗体。
这项II期开放标签研究评估了索托维单抗暴露前预防在疫苗反应受损的免疫功能低下成年人中的安全性和耐受性。2022年2月至6月期间，在美国东北部地区，由于奥密克戎BA.2亚变体的传播，参与者在治疗日（TD）1接受500mg静脉注射索托维单抗，在TD2接受2000mg静脉注射。随访持续36周（约5个半衰期），评估安全性和耐受性、药代动力学、COVID-19的发病率和严重程度以及生活质量。
93名受试者在TD1接受了500mg，其中81名在TD2接受了2000mg。3名患者报告了5起与药物相关的不良事件，4起2级输液相关反应和1起2级头痛，均迅速缓解。在35例SARS-CoV-2病例中，根据美国国立过敏和传染病研究所的序贯量表，94%的患者没有活动受限或住院情况。索托维单抗在500mg和2000mg剂量下的暴露量呈剂量依赖性增加。
索托维单抗暴露前预防具有良好的安全性，两种剂量下耐受性均良好，免疫原性低。这些发现支持单克隆抗体作为该人群COVID-19暴露前预防的安全性。
