title: NDV-3, a recombinant alum-adjuvanted vaccine for Candida and Staphylococcus aureus, is safe and immunogenic in healthy adults.
abstract: The investigational vaccine, NDV-3, contains the N-terminal portion of the Candida albicans agglutinin-like sequence 3 protein (Als3p) formulated with an aluminum hydroxide adjuvant in phosphate-buffered saline. Preclinical studies demonstrated that the Als3p vaccine antigen protects mice from oropharyngeal, vaginal and intravenous challenge with C. albicans and other selected species of Candida as well as both intravenous challenge and skin and soft tissue infection with Staphylococcus aureus. The objectives of this first-in-human Phase I clinical trial were to evaluate the safety, tolerability and immunogenicity of NDV-3 at two different antigen levels compared to a saline placebo. Forty healthy, adult subjects were randomized to receive one dose of NDV-3 containing either 30 or 300 μg of Als3p, or placebo. NDV-3 at both dose levels was safe and generally well-tolerated. Anti-Als3p total IgG and IgA1 levels for both doses reached peak levels by day 14 post vaccination, with 100% seroconversion of all vaccinated subjects. On average, NDV-3 stimulated peripheral blood mononuclear cell (PBMC) production of both IFN-γ and IL-17A, which peaked at day 7 for subjects receiving the 300 μg dose and at day 28 for those receiving the 30 μg dose. Six months after receiving the first dose of NDV-3, nineteen subjects received a second dose of NDV-3 identical to their first dose to evaluate memory B- and T-cell immune responses. The second dose resulted in a significant boost of IgG and IgA1 titers in >70% of subjects, with the biggest impact in those receiving the 30 μg dose. A memory T-cell response was also noted for IFN-γ in almost all subjects and for IL-17A in the majority of subjects. These data support the continued investigation of NDV-3 as a vaccine candidate against Candida and S. aureus infections.
authors.affiliation: NovaDigm Therapeutics, Inc., Grand Forks, ND 58202, USA.
authors.forename: Clint S
authors.initials: CS
authors.lastname: Schmidt
authors.forename: C Jo
authors.initials: CJ
authors.lastname: White
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Yeaman
authors.forename: John E
authors.initials: JE
authors.lastname: Edwards
authors.forename: John P
authors.initials: JP
authors.lastname: Hennessey
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000534:Alum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000908:Antibodies, Fungal / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D002176:Candida albicans / Q000235:genetics / Q000276:immunology*; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D010919:Placebos / Q000008:administration & dosage; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000908:Antibodies, Fungal; D005657:Fungal Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D020381:Interleukin-17; D010919:Placebos; D013209:Staphylococcal Vaccines; D014614:Vaccines, Synthetic; C041524:aluminum sulfate; D007371:Interferon-gamma