Human Antibodies Induced by an Immunotherapeutic Vaccine (NDV-3A) Containing Als3p, Abrogate Virulence Traits of Candida albicans
Year: 2017
Type: conference-abstract
Abstract: NDV-3A is a vaccine containing a recombinant version of the Candida albicans Als3 protein (Als3p) formulated with aluminum hydroxide (AlOH). A recently completed exploratory Phase 2a clinical trial of NDV-3A, referred to as NDV3A-003, showed that women with recurrent vulvovaginal candidiasis (RVVC) could be protected from recurrence of VVC for up to 12 months post-vaccination. Vaccination with NDV-3A induces a robust anamnestic immune response characterized by high anti-Als3 antibody titers when compared with placebo AlOH-vaccinated subjects. We evaluated whether these anti-Als3p antibodies could have an influence on the virulence traits of C. Albicans. Sera from patients vaccinated with NDV-3A or placebo were tested. The vaccinated subjects were further divided into those without recurrence of VVC post-vaccination (non-recurrent) vs. those who had a recurrence within the observation period (recurrent patients). In total, 98 serum samples collected from various patients were mixed with growth media at a 19:1 ratio (media:serum), and compared for their ability to impact C. Albicans, 1) adherence to plastic by XTT assay, 2) invasion of vaginal epithelial cells using fluorescent differential counting, and 3) biofilm formation on plastic and catheter material. The ability of antibodies to trigger opsonophagocytosis of C. Albicans by human neutrophils was also studied. Sera from non-recurrent patients (n = 26) abrogated hyphal elongation, adhesion to plastic, invasion of vaginal epithelial cells, and biofilm formation, significantly more than sera from recurrent patients (n = 33; P < 0.01) or placebo recipients (n = 39). Biofilm growth was prevented even after 72 hours of initial treatment. The inhibitory effect of sera was due to antibodies, since depletion of antibodies by C. Albicans adsorption resulted in loss of the inhibitory activity, while heat inactivation of sera did not. Finally, antibodies enhanced opsonophagocytosis of the fungus by human neutrophils. Anti-Als3p antibodies likely have a pivotal role in protecting against RVVC. A passive antibody therapy, or attaching of Als3 antibodies to abiotic surfaces, could prove a useful strategy against C. Albicans device-associated infections. All authors: No reported disclosures.
Source: Open Forum Infectious Diseases
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,053
OpenAlex ID: W2753081892