The anti-Candida vaccine based on the recombinant N-terminal domain of Als1p is broadly active against disseminated candidiasis

Abstract

We have previously shown that vaccination with a vaccine based on the recombinant N-terminal domain of Als1p (rAls1p-N) protected BALB/c mice against disseminated infection caused by a single strain of Candida albicans (A. S. Ibrahim, B. J. Spellberg, V. Avenissian, Y. Fu, S. G. Filler, and J. E. Edwards, Jr., Infect. Immun. 73:999-1005, 2005, and B. J. Spellberg, A. S. Ibrahim, V. Avenissian, S. G. Filler, C. Myers, Y. Fu, and J. E. Edwards, Jr., Infect. Immun. 73:6191-6193, 2005). Here we show that the rAls1p-N vaccine also improves survival of outbred mice from disseminated candidiasis and that it is active against multiple virulent strains of C. albicans and non-C. albicans spp.

FIG. 1.

rAls1p-N vaccine improves survival of outbred, CD1 mice from hematogenously disseminated candidiasis. (A) CD1 mice (n = 8 per group) were vaccinated subcutaneously with rAls1p-N (20 μg) plus CFA or with CFA alone and infected via the tail vein with C. albicans SC5314 14 days after the boost. (B) CD1 mice (n = 8 per group) were vaccinated subcutaneously with rAls1p-N at various doses with alum or with alum alone and infected via the tail vein with C. albicans SC5314 14 days after the boost. The inoculum for panels A and B was 5 × 10⁵ blastospores. *, P < 0.05 versus adjuvant control by log rank test.

FIG. 2.

rAls1p-N vaccine improves the survival of BALB/c mice infected with one of several bloodstream isolates of C. albicans. Shown is survival of BALB/c mice immunized with rAls1p-N (20 μg) plus CFA versus immunized with CFA alone and infected via the tail vein with C. albicans 15563 (7 × 10⁵ blastospores), 16240 (4 × 10⁵ blastospores), or 36082 (4 × 10⁵ blastospores) (n = 8 mice per group). *, P < 0.05 versus adjuvant control by log rank test.

FIG. 3.

rAls1p-N vaccine reduces tissue fungal burden in BALB/c mice infected with several non-C. albicans strains of Candida. BALB/c mice (n = 5 per group) were vaccinated with CFA or CFA plus rAls1p-N (20 μg) and infected via the tail vein with C. glabrata, C. krusei, C. parapsilosis, or C. tropicalis. Infectious inocula are shown in parentheses below the species names. Kidney fungal burden was determined on day 5 postinfection. The y axis reflects the lower limit of detection of the assay. *, P < 0.05 versus adjuvant control by nonparametric Steel test for multiple comparisons.