Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, JS 210000, China.
Third Military Medical University, Chongqing 400038, China.
Vaccine. 2022 May 20;40(23):3216-3227. doi: 10.1016/j.vaccine.2022.04.034. Epub 2022 Apr 23.
Staphylococcus aureus is an important pathogen that causes hospital and community infections. To control Staphylococcus aureus infection and reduce the usage of antibiotics, we evaluated the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in healthy adults.
We conducted a randomized, double-blind, placebo-controlled phase 1a study and a randomized, open-label phase 1b study. In phase 1a, we randomly allocated 144 healthy participants in a ratio of 1:1:1:1 to receive the low-(60 μg), middle-(120 μg), and high-dose (240 μg) vaccine or placebo at day 0, 3, 7 and 14. In phase 1b, 144 healthy participants were randomly allocated at a ratio of 1:1:1:1 to receive 0-3-7, 0/0-7, 0/0-3-7, 0/0-7-14 regimens to estimate the optimal strategy. The primary study endpoint was the incidence of solicited adverse events post-vaccination. The immunogenicity endpoints included the level of specific antibodies to five antigens after vaccination, as well as the cellular immune responses and functional antibodies.
There were 31 (86%), 30 (83%), and 32 (89%) of 36 participants in the low-, middle-, and high-dose group reported solicited adverse events, respectively, most of the adverse events were mild or moderate. In phase 1b, the dose-adjusted rFSAV (90 μg) showed a better safety profile in the four immune procedures, and no vaccine-related serious adverse events were reported. The antigen-specific binding antibodies started to increase at day 7 and reached the peak around day 14 to 21. The cellular immune responses and functional antibodies also were substantially above background levels.
rFSAV is safe, well tolerated in healthy adults, elicits rapid and robust specific humoral and cellular immune responses with unconventional immunization procedure in phase 1a and 1b. It deserves to be noted and further explored.
NCT02804711 and NCT03966040.
金黄色葡萄球菌是引起医院和社区感染的重要病原体。为了控制金黄色葡萄球菌感染和减少抗生素的使用，我们评估了一种重组五抗原金黄色葡萄球菌疫苗（rFSAV）在健康成年人中的安全性和免疫原性。
我们进行了一项随机、双盲、安慰剂对照的 1a 期研究和一项随机、开放标签的 1b 期研究。在 1a 期研究中，我们将 144 名健康参与者按照 1:1:1:1 的比例随机分配，分别在第 0、3、7 和 14 天接受低（60μg）、中（120μg）和高剂量（240μg）疫苗或安慰剂。在 1b 期研究中，144 名健康参与者按照 1:1:1:1 的比例随机分配，接受 0-3-7、0/0-7、0/0-3-7、0/0-7-14 方案，以评估最佳策略。主要研究终点是疫苗接种后不良事件的发生率。免疫原性终点包括接种后五种抗原特异性抗体水平以及细胞免疫反应和功能抗体。
低、中、高剂量组分别有 31（86%）、30（83%）和 32（89%）名参与者报告了 36 名参与者中的不良事件，大多数不良事件为轻度或中度。在 1b 期研究中，剂量调整后的 rFSAV（90μg）在四种免疫程序中显示出更好的安全性，且无疫苗相关严重不良事件报告。抗原特异性结合抗体于第 7 天开始增加，于第 14 至 21 天达到峰值。细胞免疫反应和功能抗体也明显高于背景水平。
rFSAV 在健康成年人中安全、耐受良好，在 1a 期和 1b 期采用非常规免疫程序可快速、强烈地诱导特异性体液和细胞免疫反应。值得注意和进一步探索。
NCT02804711 和 NCT03966040。
