The anti-Candida albicans vaccine composed of the recombinant N terminus of Als1p reduces fungal burden and improves survival in both immunocompetent and immunocompromised mice

Abstract

We have previously shown that intraperitoneal vaccination with the recombinant N terminus of Als1p (rAls1p-N) modestly improves survival during murine disseminated candidiasis. We now report marked efficacy with subcutaneous rAls1p-N vaccination. Efficacy is retained in neutropenic and corticosteroid-treated mice. The rAls1p-N vaccine is a promising candidate for the prevention of invasive candidiasis.

FIG. 1.

Subcutaneous vaccination with rAls1p-N induces an in vivo DTH response in immunocompetent mice. Footpad swelling was assessed 24 h after injection of 50 μg of rAls1p-N into the footpad in BALB/c mice (n = 10 per group). Median values are displayed as horizontal black bars. *, P = 0.002 versus control by Wilcoxon rank sum test.

FIG. 2.

The rAls1p-N vaccine improves survival of immunocompetent mice with hematogenously disseminated candidiasis and reduces tissue fungal burden. (A) Survival of vaccinated or control BALB/c mice (n = 7 or 10 per group for an inoculum of 2.5 × 10⁵ or 5 × 10⁵, respectively) subsequently infected via the tail vein with C. albicans. Each experiment was terminated at 30 days postinfection, with all remaining mice appearing well. *, P < 0.05 versus control by log rank test. (B) Kidney fungal burden in BALB/c mice (n = 7 per group) infected via the tail vein with 5 × 10⁵ blastospores of C. albicans. The y axis reflects the lower limit of detection of the assay. Median values are displayed as horizontal black bars. *, P = 0.01 versus control by Wilxocon rank sum test.

FIG. 3.

The rAls1p-N vaccine induces a DTH reaction in neutropenic mice and improves their survival during subsequent hematogenously disseminated candidiasis. (A) Footpad swelling was assessed 24 h after injection of 50 μg of rAls1p-N into the footpad in BALB/c mice (n = 10 for control, n = 8 for rAls1p-N). *, P = 0.006 versus control by Wilcoxon rank sum test. (B) Survival of neutropenic BALB/c mice (n = 16 per group from two experiments) infected with 2.5 × 10⁴ blastospores of C. albicans. *, P = 0.007 versus adjuvant control by log rank test.

FIG. 4.

The rAls1p-N vaccine diminishes the severity of histopathological fungal lesions on the tongues of mice with oropharyngeal candidiasis. n = 4 mice per group. Inflammatory score was generated by a blinded observer as described in the text. *, P = 0.03 by Wilcoxon rank sum test.