A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis-A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial
A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis-A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial
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DOI：
10.1093/cid/ciy185
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发表时间：
2018-06-15
影响因子：
11.8
通讯作者：
Hennessey, John P., Jr.
中科院分区：
文献类型：
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作者：
Edwards, John E., Jr.;Schwartz, Michael M.;Hennessey, John P., Jr.
背景复发性外阴阴道念珠菌病（RVVC）是一种粘膜念珠菌感染的问题形式，其特征是每年反复发作。白色念珠菌是RVVC最常见的原因。目前，没有针对RVVC的免疫治疗。这项探索性随机、双盲、安慰剂对照试验评价了含有重组C.白念珠菌粘附素/侵袭素蛋白预防RVVC的研究在188名患有RVVC的女性中进行的研究（n = 178可评估）表明，1次肌内注射NDV-3A是安全的，并产生快速和强大的B细胞和T细胞免疫应答。事后探索性分析显示，对于年龄< 40岁的患者亚组（n = 137），在接种疫苗后12个月，无梅毒患者的百分比在统计学上显著增加（42%接种疫苗vs 22%安慰剂; P = 0.03），首次症状发作的中位时间加倍（210天接种疫苗vs 105天安慰剂）。对可评估患者的分析，包括年龄< 40岁（77%）和≥ 40岁（23%）的患者，NDV-3A与安慰剂相比有积极影响的趋势（P = 0.099）。在这项前所未有的人类真菌疫苗有效性研究中，给予RVVC女性的NDV-3A是安全的，具有高度免疫原性，并降低了年龄< 40岁女性外阴阴道念珠菌病症状发作的频率长达12个月。这些结果支持NDV-3A疫苗的进一步开发，并为RVVC的免疫管理提供有意义的临床终点指导。
Background. Recurrent vulvovaginal candidiasis (RVVC) is a problematic form of mucosal Candida infection, characterized by repeated episodes per year. Candida albicans is the most common cause of RVVC. Currently, there are no immunotherapeutic treatments for RVVC.Methods. This exploratory randomized, double-blind, placebo-controlled trial evaluated an immunotherapeutic vaccine (NDV-3A) containing a recombinant C. albicans adhesin/invasin protein for prevention of RVVC.Results. The study in 188 women with RVVC (n = 178 evaluable) showed that 1 intramuscular dose of NDV-3A was safe and generated rapid and robust B-and T-cell immune responses. Post hoc exploratory analyses revealed a statistically significant increase in the percentage of symptom-free patients at 12 months after vaccination (42% vaccinated vs 22% placebo; P = .03) and a doubling in median time to first symptomatic episode (210 days vaccinated vs 105 days placebo) for the subset of patients aged < 40 years (n = 137). The analysis of evaluable patients, which combined patients aged < 40 years (77%) and = 40 years (23%), trended toward a positive impact of NDV-3A versus placebo (P = .099).Conclusions. In this unprecedented study of the effectiveness of a fungal vaccine in humans, NDV-3A administered to women with RVVC was safe and highly immunogenic and reduced the frequency of symptomatic episodes of vulvovaginal candidiasis for up to 12 months in women aged < 40 years. These results support further development of NDV-3A vaccine and provide guidance for meaningful clinical endpoints for immunotherapeutic management of RVVC.