Comparison of Two Candida Mannan Vaccines: The Role of Complement in Protection against Disseminated Candidiasis

다국어 초록 (Multilingual Abstract)

We have previously shown that Candida albicans mannan extract encapsulated in liposomes [Lipo-mann] or conjugated to a protein (bovine serum albumin) [Conju-mann] induces the production of antibody in BALB/c mice with normal complement system that protect against disseminated candidiasis. In this present study, we determined the protective abilities of two formulae in a C5-deficient mouse model of disseminated candidiasis. It is known that the lack of C5 is known to aggravate candidal infection. In experiments, BALB/c or C5-deficient mice-DBA/2J and AKR mice, were immunized with one of the formulae before intravenous challenge with live C. albicans yeast cells and their degrees of survivability were measured.
Results showed that Conju-mann was 100% protective in BALB/c mice against disseminated candidiasis, whereas only 60% of Lipo-mann immunized mice survived the entire 50 day observation period (p < 0.05). With the DBA/2J strain, Conju-mann resulted in a partial protection, but Lipo-mann had no protection. The conjugate vaccine enhanced the resistance of AKR mice, which resulted in three survivors of the five Conju-immunized AKR mice until the end of 50 day observation period (p < 0.05). Lipo-mann showed little protection in AKR mice. By agglutination analyses, it was determined that there was the same level of production of polyclonal antisera specific to the mannan regardless of the mouse strains. All data indicate that both formulations require complement in the protection. However, Conju-mann appears to be superior to Lipo-mann because the conjugate vaccine is protective even in the absence of C5. These observations suggest that the conjugate vaccine can be an excellent vaccine formulation against C. alibicans infections.

참고문헌 (Reference)

1 한용문, "Th1 immunity induction by ginsenoside Re involves in protection of mice against disseminated candidiasis due to Candida albicans" ELSEVIER SCIENCE BV 14 (14): 481-486, 201212

2 한용문, "Synergic anticandidal effect of epigallocatechin-O-gallate combined with amphotericin B in a murine model of disseminated candidiasis and its anticandidal mechanism" PHARMACEUTICAL SOC JAPAN 30 : 1693-1696, 2007

3 Ashman, R. B., "Strain-dependent differences in host response to Candida albicans infection in mice are related to organ susceptibility and infectious load" 64 : 1866-1869, 1996

4 Ashman, R. B., "Role of complement C5 and T lymphocytes in pathogenesis of disseminated and mucosal candidiasis in susceptible DBA/2 mice" 34 : 103-113, 2003

5 한용문, "Protection against candidiasis by an immunoglobulin G3 (IgG3) monoclonal antibody specific for the same mannotriose as an IgM protective antibody" AMER SOC MICROBIOLOGY 68 (68): 1649-1654, 200003

6 Costantino, P. J., "Humoral immune responses to systemic Candida albicans infection in inbred mouse strains" 73 : 125-133, 1995

7 Lee, J. H., "Ginsenoside Rg1 helps mice resist to disseminated candidiasis by Th1 type differentiation of CD4+ T cell" ELSEVIER SCIENCE BV 6 : 1424-1430, 2006

8 Han, Y., "Ginkgo terpene component has an anti-inflammatory effect on Candida albicans-caused arthritic inflammation" ELSEVIER SCIENCE BV 5 : 1049-1056, 2005

9 Radovanovic, I., "Genetic control of susceptibility to infection with Candida albicans in mice" 6 : e18957-, 2011

10 Kanbe, T., "Evidence for adhesin activity in the acid-stable moiety of the phosphomannoprotein cell wall complex of Candida albicans" 62 : 1662-1668, 1994

11 한용문, "Efficacy of combination immunotherapy of IgM MAb B6.1 and amphotericin B against disseminated candidiasis" ELSEVIER SCIENCE BV 10 : 1526-1531, 201012

12 한용문, "EVIDENCE THAT MANNANS OF CANDIDA-ALBICANS ARE RESPONSIBLE FOR ADHERENCE OF YEAST FORMS TO SPLEEN AND LYMPH-NODE TISSUE" AMER SOC MICROBIOLOGY 61 (61): 2578-2584, 199306

13 Hazen, K. C., "Differential adherence of hydrophobic and hydrophilic Candida albicans yeast cells to mouse tissues" 59 : 907-912, 1991

14 Cheng, S. C., "Complement plays acentral role in Candida albicans-induced cytokine production by human PBMCs" 42 : 993-1004, 2012

15 한용문, "Complement is essential for protection by an IgM and an IgG3 monoclonal antibody against experimental, hematogenously disseminated candidiasis" AMER ASSOC IMMUNOLOGISTS 167 (167): 1550-1557, 2001

16 Lee, J. H., "Chlorogenic acid, a polyphenolic compound, treat mice with septic arthritis caused by Candida albicans" 8 : 681-685, 2008

17 Mullick, A., "Cardiac failure in C5-deficient A/J mice after Candida albicans infection" 74 : 4439-4451, 2006

18 한용문, "Candida albicans mannan extract-protein conjugates induce a protective immune response against experimental candidiasis" UNIV CHICAGO PRESS 179 (179): 1477-1484, 199906

19 한용문, "Biochemical characterization of Candida albicans epitopes that can elicit protective and nonprotective antibodies" AMER SOC MICROBIOLOGY 65 (65): 4100-4107, 199710

20 Han, Y., "Binding of Candida albicans yeast cells to mouse popliteal lymph node tissue is mediated by macrophages" 61 : 3244-3249, 1993

21 한용문, "Berberine synergy with amphotericin B against disseminated candidiasis in mice" PHARMACEUTICAL SOC JAPAN 28 : 541-544, 2005

22 Han, Y., "Antibody response that protects against disseminated candidiasis" 63 : 2714-2719, 1995

23 한용문, "A vaccine and monoclonal antibodies that enhance mouse resistance to Candida albicans vaginal infection" AMER SOC MICROBIOLOGY 66 (66): 5771-5776, 199812

24 Caesar-TonThat, T. C., "A monoclonal antibody to Candida albicans enhances mouse neutrophil candidacidal activity" 65 : 5354-5357, 1997