Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
Vaccine. 2022 Mar 15;40(12):1864-1871. doi: 10.1016/j.vaccine.2022.01.047. Epub 2022 Feb 10.
The potential use of Bacillus anthracis as a bioterrorism weapon requires a safe and effective vaccine that can be immediately distributed for mass vaccination. Protective antigen (PA), a principal component of virulence factors edema toxin and lethal toxin of B. anthracis, has been the topic of extensive research. Previously, full-length PA (PA83) was manufactured using a transient plant-based expression system. Immunization with this PA83 antigen formulated with Alhydrogel® adjuvant elicited strong neutralizing immune responses in mice and rabbits and protected 100% of rabbits from a lethal aerosolized B. anthracis challenge. This Phase 1 study evaluates this vaccine's safety and immunogenicity in healthy human volunteers.
This first-in-human, single-blind, Phase 1 study was performed at a single center to investigate the safety, reactogenicity, and immunogenicity of the plant-derived PA83-FhCMB vaccine at four escalating dose levels (12.5, 25, 50 or 100 µg) with Alhydrogel® in healthy adults 18-49 years of age (inclusive). Recipients received three doses of vaccine intramuscularly at 28-day intervals. Safety was evaluated on days 3, 7, and 14 following vaccination. Immunogenicity was assessed using an enzyme-linked immunosorbent assay (ELISA) and a toxin neutralizing antibody (TNA) assay on days 0, 14, 28, 56, 84, and 180.
All four-dose ranges were safe and immunogenic, with no related serious adverse events observed. Peak ELISA Geometric Mean Concentration (GMC) and TNA ED Geometric Mean Titer (GMT) were noted at Day 84, 1 month after the final dose, with the most robust response detected in the highest dose group. Antibody responses decreased by Day 180 across all dose groups. Long-term immunogenicity data beyond six months was not collected.
This is the first study demonstrating a plant-derived subunit anthrax vaccine's safety and immunogenicity in healthy adults. The results support further clinical investigation of the PA83-FhCMB vaccine. ClinicalTrials.gov identifier. NCT02239172.
炭疽杆菌作为生物恐怖主义武器的潜在用途需要一种安全有效的疫苗，以便能够立即分发用于大规模接种。保护性抗原（PA）是炭疽杆菌水肿毒素和致死毒素的主要毒性因子，已成为广泛研究的主题。以前，全长 PA（PA83）是使用瞬时植物表达系统制造的。用 Alhydrogel®佐剂配制的这种 PA83 抗原免疫接种可在小鼠和兔中引起强烈的中和免疫应答，并可保护 100%的兔免受致死性气溶胶炭疽杆菌的攻击。这项 I 期研究评估了这种疫苗在健康志愿者中的安全性和免疫原性。
这是一项在单一中心进行的首次人体、单盲、I 期研究，旨在研究植物源性 PA83-FhCMB 疫苗在四种递增剂量水平（12.5、25、50 或 100μg）下与 Alhydrogel®联合使用在 18-49 岁健康成年人中的安全性、反应原性和免疫原性（含）。受种者每隔 28 天接受三次肌肉内疫苗接种。接种后第 3、7 和 14 天评估安全性。使用酶联免疫吸附测定（ELISA）和毒素中和抗体（TNA）测定在第 0、14、28、56、84 和 180 天评估免疫原性。
所有四个剂量范围均安全且具有免疫原性，未观察到与疫苗相关的严重不良事件。在最后一次给药后 1 个月，即第 84 天，观察到 ELISA 几何平均浓度（GMC）和 TNA ED 几何平均滴度（GMT）的峰值，在最高剂量组中检测到最强大的反应。所有剂量组的抗体反应在第 180 天下降。未收集超过六个月的长期免疫原性数据。
这是第一项证明植物源性亚单位炭疽疫苗在健康成年人中的安全性和免疫原性的研究。结果支持进一步临床研究 PA83-FhCMB 疫苗。临床试验.gov 标识符。NCT02239172。
