title: Antibody titer threshold predicts anti-candidal vaccine efficacy even though the mechanism of protection is induction of cell-mediated immunity.
abstract: We previously reported that vaccination with Freund's adjuvant plus the recombinant N-terminus of the candidal adhesin, Als3p (rAls3p-N), protects mice from disseminated candidiasis. Here we report that the rAls3p-N vaccine is effective when combined with aluminum hydroxide adjuvant. Antibody titers of > or =1:6400 accurately predicted protection from infection. Nevertheless, neither B lymphocytes nor serum from immunized animals transferred protection to vaccine-naive animals. In contrast, CD3(+), CD4(+), or CD8(+) T lymphocytes from immunized animals transferred protection, and the vaccine was efficacious in IL-4-deficient mice but not in IFN-gamma-deficient mice. These data have significant implications for the development and interpretation of vaccine surrogate markers.
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles, Medical Center, Torrance, CA 90502, USA. bspellberg@labiomed.org
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Valentina
authors.initials: V
authors.lastname: Avanesian
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.forename: Peter
authors.initials: P
authors.lastname: Lipke
authors.forename: Henry
authors.initials: H
authors.lastname: Otoo
authors.forename: Tiffany
authors.initials: T
authors.lastname: Ho
authors.forename: John E
authors.initials: JE
authors.lastname: Edwards
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D019264:Adoptive Transfer; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002177:Candidiasis / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D005656:Fungal Proteins / Q000276:immunology*; D005657:Fungal Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000172:deficiency; D015847:Interleukin-4 / Q000172:deficiency; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C113620:ALS3 protein, Candida albicans; D000276:Adjuvants, Immunologic; D000908:Antibodies, Fungal; D015415:Biomarkers; D017252:CD3 Complex; D005656:Fungal Proteins; D005657:Fungal Vaccines; D015847:Interleukin-4; D000536:Aluminum Hydroxide; D007371:Interferon-gamma