Immunization with the Candida albicansMembrane Fraction and in Combination with Fluconazole Protects against Systemic Fungal Infections

DOI: 10.1128/AAC.44.2.243-247.2000

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Fig. 1.
Anticandida activity of CMA immunization combined with FLC. Mice (n = 10) immunized with CMA or saline emulsified in IFA were infected with C. albicans 7 days after the last immunization and given 4 oral administrations of FLC or saline as a control. Mice were sacrificed 7 days after the infection to determine CFU in kidneys. Student's t test results: ∗, P < 0.001 versus control group injected with saline; +, P < 0.001 versus CMA; ++, P < 0.001 versus FLC at 12.5 mg/kg; +++, P < 0.001 versus FLC at 50 mg/kg.
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Fig. 2.
Effect of depletion of CD4⁺ or CD8⁺ cells or IFN-γ by MAbs on the activity of combined CMA immunization and FLC. Mice (n = 5) that received two weekly immunizations with CMA or saline emulsified in IFA were infected with C. albicans 3 weeks after the last immunization and given four oral administrations of 50 mg of FLC or saline per kg as a control once daily. Mice were sacrificed 7 days after infection to determine the CFU in the kidneys. Mice were given each MAb three times as described in Materials and Methods. Data are representative of two individual experiments. Student's ttest results: ∗, P = 0.0264; ∗∗, P = 0.0088; ∗∗∗, P = 0.0066; +, P = 0.0012; ++, P <0.001 versus control group injected with saline.

Table 1.

Antifungal activity of immunization with CMA against systemic infections by C. albicansor A. fumigatus^a

↵a Mice received two (× 2) or three (× 3) weekly immunizations with CFA or IFA as described in Materials and Methods. Mice were infected with C. albicans (2.5 × 10⁵ cells/mouse) 7 days after the last immunization. Survival was observed for 30 days after infection. NT, not tested.
↵b Generalized Wilcoxon test versus control group injected with saline.

Table 2.

Effect of immunosuppression by CY on resistance to systemic candidiasis induced by CMA immunization^a

Infection (no. of cells/mouse)	Immunization	MSD	No. of survivors/no. treated (P^b)
1 × 10⁴	Saline	>20.6	2/5
	CMA	>30.0	5/5 (<0.01)
5 × 10⁴	Saline	1.9	0/10
	CMA	>24.8	7/10 (<0.01)
2.5 × 10⁵	Saline	0	0/5
	CMA	6.8	1/5 (0.05)

↵a Mice immunized with CMA emulsified in IFA were infected i.v. with C. albicans cells 7 days after the last immunization. CY was given 4 days before infection. Survival was observed for 30 days after infection.
↵b Cox-Mantel test versus the respective control group injected with saline.

Table 3.

Prolonged survival of mice systemically infected withA. fumigatus after treatment with CMA, FLC, or a combination of both^a

Group	CMA	FLC (mg/kg)	MSD	No. of survivors/no. of treated mice	P^bversus:
Group	CMA	FLC (mg/kg)	MSD	No. of survivors/no. of treated mice	Group 1	Groups 3, 4, and 5
1	−	0	7.0	0/5
2	+	0	>20.6	2/5	0.0082
3	−	3.1	8.4	0/5	0.4354
4	−	12.5	11.6	0/5	0.0434
5	−	50	>20.2	1/5	0.0086
6	+	3.1	>25.6	3/5	0.0078	0.0098
7	+	12.5	>28.0	4/5	0.0068	0.0094
8	+	50	>30.0	5/5	0.0052	0.0188

↵a Mice that received three weekly immunizations with CMA (+) or saline (−) emulsified in CFA first and IFA thereafter were infected by A. fumigatus 7 days after the last immunization. Thereafter, they received FLC (3.1, 12.5, or 50 mg/kg once daily) for 4 consecutive days or saline (0 mg/kg) as a control. Survival was observed for 30 days after infection. Data are representative of two individual experiments.
↵b Generalized Wilcoxon test versus control (group 1) or the respective group treated with FLC (groups 3, 4, or 5). There were no significant differences between the CMA immunization only group (group 2) and the groups given CMA combined with FLC (groups 6, 7, or 8).