Antibody Titer Threshold Predicts Anti‐Candidal Vaccine Efficacy Even though the Mechanism of Protection Is Induction of Cell‐Mediated Immunity
1Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor–University of California, Los Angeles, Medical Center, Torrance, and the 2David Geffen School of Medicine at University of California, Los Angeles; 3Department of Biology, Brooklyn College, Brooklyn, New York
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.
Received 22 August 2007; accepted 29 October 2007; electronically published 29 February 2008.
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(See the editorial commentary by Galgiani, on pages 938–40.)
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Online publication date: 1-Apr-2008.
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Presented in part: 47th Interscience Convention on Antimicrobial Agents and Chemotherapy (ICAAC), Chicago, IL, September 2007 (abstract B-1447).
Potential conflicts of interest: B.J.S, A.S.I, Y.F, and J.E.E. own equity in NovaDigm Therapeutics, Inc., which is developing vaccine technologies. NovaDigm Therapeutics, Inc. provided no financial support for these studies.
Financial support: Public Health Service grants (R01 AI19990 and AI063382 to J.E.E.; R01 AI072052 and K08 AI060641 to B.J.S.); Bristol Myers Squibb (unrestricted Freedom to Discover Grant for Infectious Disease to J.E.E.); Burroughs Wellcome (New Investigator Award in Molecular Pathogenic Mycology to A.S.I.); Los Angeles Biomedical Research Institute (Liu Young Investigator Award to B.J.S.); American Heart Association (Beginning Grant‐in‐Aid 0665154Y to B.J.S.).