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...

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Bibliographic Details
Published in:The Journal of infectious diseases 2008-04, Vol.197 (7), p.967-971
Main Authors: Spellberg, Brad, Ibrahim, Ashraf S., Lin, Lin, Avanesian, Valentina, Fu, Yue, Lipke, Peter, Otoo, Henry, Ho, Tiffany, Edwards, John E.
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - administration & dosage
Adoptive Transfer
Aluminum
Aluminum Hydroxide - administration & dosage
Animals
Antibodies
Antibodies, Fungal - blood
B-Lymphocytes - immunology
Biomarkers
Candidiasis
Candidiasis - immunology
Candidiasis - prevention & control
CD3 Complex - analysis
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Dosage
Female
Fungal Proteins - immunology
Fungal Vaccines - immunology
Fungi
Hydroxides
Infections
Interferon-gamma - deficiency
Interleukin-4 - deficiency
Lymphocytes
Mice
Mice, Inbred BALB C
Survival Analysis
T-Lymphocyte Subsets - immunology
Vaccination
Veins
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Summary: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 ⩾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-γ–deficient mice. These data have significant implications for the development and interpretation of vaccine surrogate markers
ISSN:0022-1899
1537-6613
DOI:10.1086/529204