Clinical Advisory Unit, Bio-Manguinhos/Fiocruz, Rio de Janeiro, RJ, Brazil.
National School of Public Health, Fiocruz, Rio de Janeiro, RJ, Brazil.
Braz J Infect Dis. 2021 Nov-Dec;25(6):101652. doi: 10.1016/j.bjid.2021.101652. Epub 2021 Nov 16.
Meningococcal disease by serogroup B has been a public health problem in Brazil in the last decades. The Brazilian Oswaldo Cruz Foundation has been working to develop a vaccine with detergent-treated outer membrane vesicles (OMV) and detoxified endotoxin (dLOS) from Neisseria meningitidis serogroup B prevalent strains. A phase I study, enrolling 26 adults (18-44 years of age) was performed using experimental vaccines combining B components and aluminum hydroxide as adjuvant. It was a dose escalation study testing vaccines made of 25, 50, and 100 µg OMV protein/mL (sum of both strains) and dLOS in half amount of total protein concentration, with three doses given two months apart. Adverse events were mild/moderate with frequency increasing with the amount of antigens. Pain in the site of injection was the most frequent reaction in all doses, reported in more than the 85% across vaccine groups. Considering all injections, cephalea was the most common systemic adverse event, detected in 11.1%, 17.2% and 32.1%, respectively with doses of 12.5 μg, 25 μg and 50 μg. High titers of total IgG (ELISA) were observed for the vaccine components before vaccination. Protective levels of bactericidal antibodies (titer ≥1:4) for both vaccine strains were also present. Considering a 4-fold increase of IgG titers compared to pre-immune values (seroconversion), 50%-70% of those who received intermediate and highest doses of antigens presented satisfactory response for OMV of N44/89 strain. The lowest dose vaccine induced no seroconversion for strain N44/89, and 11% for strain N603/95. For the three vaccines doses, 25% of seroconversion, in total IgG against LOS, was observed. Increased antibody bactericidal activity was observed for both strains in higher antigen concentrations. For IgG against LOS, all vaccine formulations showed 25% of seroconversion. In conclusion, MenB-Bio experimental vaccines were well tolerated and immunogenic, thus allowing phase II studies.
B 群脑膜炎球菌疾病在过去几十年一直是巴西的一个公共卫生问题。巴西奥斯瓦尔多·克鲁兹基金会一直在努力开发一种疫苗，该疫苗使用 B 群脑膜炎奈瑟菌流行株的去污处理外膜囊泡（OMV）和解毒内毒素（dLOS）。一项纳入 26 名成年人（18-44 岁）的 I 期研究使用了联合 B 群成分和氢氧化铝佐剂的实验疫苗。这是一项剂量递增研究，测试了由 25、50 和 100μg OMV 蛋白/mL（两种菌株总和）和总蛋白浓度减半的 dLOS 组成的疫苗，三剂间隔两个月。不良事件为轻度/中度，随着抗原数量的增加而增加。在所有剂量中，注射部位疼痛是最常见的反应，在疫苗组中超过 85%的人报告了这种反应。考虑到所有注射，头痛是最常见的全身不良反应，在 12.5μg、25μg 和 50μg 剂量下，分别有 11.1%、17.2%和 32.1%的人出现这种反应。在接种疫苗前，观察到针对疫苗成分的总 IgG（ELISA）的高滴度。两种疫苗株的杀菌抗体（效价≥1:4）的保护性水平也存在。考虑到与免疫前相比 IgG 滴度增加了 4 倍（血清转化率），接受中等和最高抗原剂量的人中，有 50%-70%的人对 N44/89 株的 OMV 表现出满意的反应。最低剂量的疫苗对 N44/89 株没有诱导血清转化率，对 N603/95 株的血清转化率为 11%。在三种疫苗剂量下，总 IgG 对 LOS 的血清转化率为 25%。在较高的抗原浓度下，观察到针对两种菌株的抗体杀菌活性增加。对于针对 LOS 的 IgG，所有疫苗配方的血清转化率均为 25%。总之，MenB-Bio 实验疫苗具有良好的耐受性和免疫原性，因此可以进行 II 期研究。
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