Uppuluri Priya, Singh Shakti, Alqarihi Abdullah, Schmidt Clint S, Hennessey John P, Yeaman Michael R, Filler Scott G, Edwards John E, Ibrahim Ashraf S
Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, United States.
David Geffen School of Medicine at University of California, Los Angeles, CA, United States.
Front Immunol. 2018 Jun 15;9:1349. doi: 10.3389/fimmu.2018.01349. eCollection 2018.
A Phase 1b/2a clinical trial of NDV-3A vaccine containing a recombinant Als3 protein formulated with alum protected women <40 years old from recurrent vulvovaginal candidiasis (RVVC). We investigated the potential use of anti-Als3p sera as surrogate marker of NDV-3A efficacy. Pre- and post-vaccination sera from subjects who experienced recurrence of vulvovaginal candidiasis (R) vs. those who were recurrence-free [non-recurrent (NR)] were evaluated. Anti-Als3p antisera obtained were evaluated for (1) titer and subclass profile and (2) their ability to influence virulence traits including hyphal elongation, adherence to plastic, invasion of vaginal epithelial cells, biofilm formation on plastic and catheter material, and susceptibility to neutrophil killing . Serum IgG titers in NR patients were consistently higher than in R patients, particularly for anti-Als3 subclass IgG2. Sera from vaccinated NR patients reduced hyphal elongation, adhesion to plastic, invasion of vaginal epithelial cells, and biofilm formation significantly more than pre-immune sera, or sera from R- or placebo-group subjects. Pre-adsorption of sera with germ tubes eliminated these effects, while heat inactivation did not. Finally, sera from NR subjects enhanced neutrophil-mediated killing of relative to pre-immune sera or sera from R patients. Our results suggest that higher Als3p antibody titers are associated with protection from RVVC, attenuate virulence, and augment immune clearance of the fungus . Thus, Als3p serum IgG antibodies are likely useful markers of efficacy in RVVC patients vaccinated with NDV-3A.
一项1b/2a期临床试验表明，含明矾配制的重组Als3蛋白的新城疫病毒3A（NDV-3A）疫苗可保护40岁以下女性免受复发性外阴阴道念珠菌病（RVVC）的侵害。我们研究了抗Als3p血清作为NDV-3A疗效替代标志物的潜在用途。对经历外阴阴道念珠菌病复发（R）的受试者与无复发[非复发性（NR）]的受试者在接种疫苗前后的血清进行了评估。对获得的抗Als3p抗血清进行了以下评估：（1）滴度和亚类谱，以及（2）它们影响毒力特征的能力，包括菌丝伸长、对塑料的粘附、对阴道上皮细胞的侵袭、在塑料和导管材料上形成生物膜，以及对中性粒细胞杀伤的敏感性。NR患者的血清IgG滴度始终高于R患者，尤其是抗Als3亚类IgG2。接种疫苗的NR患者的血清比免疫前血清、R组或安慰剂组受试者的血清更显著地降低了菌丝伸长、对塑料的粘附、对阴道上皮细胞的侵袭和生物膜形成。用芽管对血清进行预吸附消除了这些作用，而热灭活则没有。最后，与免疫前血清或R患者的血清相比，NR受试者的血清增强了中性粒细胞介导的对……的杀伤作用。我们的结果表明，较高的Als3p抗体滴度与预防RVVC、减弱毒力以及增强真菌的免疫清除有关。因此，Als3p血清IgG抗体可能是接种NDV-3A的RVVC患者疗效的有用标志物。
