Antibody titer threshold predicts anti-candidal vaccine efficacy even though the mechanism of protection is induction of cell-mediated immunity.
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.
Spellberg
Brad
B
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
Ibrahim
Ashraf S
AS
Lin
Lin
L
Avanesian
Valentina
V
Fu
Yue
Y
Lipke
Peter
P
Otoo
Henry
H
Ho
Tiffany
T
Edwards
John E
JE
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
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