Antibodies against Candida: potential therapeutics?

doi:10.1016/0966-842X(96)10056-1

Trends in Microbiology

Volume 4, Issue 9, September 1996, Pages 354-358

https://doi.org/10.1016/0966-842X(96)10056-1 Get rights and content

Abstract

For many years, there has been controversy over the role of antibodies in immunity to Candida, but recently specific antibodies to mannoproteins and hsp90 have been shown to be protective against murine candidiasis. Combined with technical advances in antibody engineering, this raises the possibility of harnessing such antibodies into a new range of therapeutics.

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Cited by (47)

Structural characterization of low molecular weight polysaccharide from Astragalus membranaceus and its immunologic enhancement in recombinant protein vaccine against systemic candidiasis
2016, Carbohydrate Polymers
Citation Excerpt :
Thus, antifungal vaccines is currently considered the most attractive strategy (Brown et al., 2012Brown, Denning, & Levitz, 2012; Netea & Brown, 2012). It was reported that antibodies of 47 kDa antigen against epitope C (LKVIRK), which is a breakdown product of fungal heat shock protein 90 (HSP90), are protective in systemic candidiasis (Burnie & Matthews, 2003, 2004; Matthews & Burnie, 1996, 2001, 2005). The results from Matthews, Hodgetts, and Burnie, (1995) and Yang et al. (2005) further revealed that epitope C (LKVIRK) can confer protective immune responses against systemic candidiasis.
Structure and immunologic enhancement of low molecular weight polysaccharide (LM_W-ASP) isolated from the root of Astragalus membranaceus (Fisch) Bge. Were detected in recombinant protein vaccine. Structure analysis of LM_W-ASP revealed that LM_W-ASP (M_w = 5.6 kDa) was an acid heteropolysaccharide, which consisted of Glc, Gal, Ara, Xyl and GalA in ratio of 10.0：1.3：1.7：1.0：0.9. Recombinant protein (rP-HSP90C) contained epitope C (LKVIRK) from heat shock protein 90 (HSP90) of Candida albicans was used as a vaccine. The results indicated that LM_W-ASP significantly promoted specific antibody titers IgG, IgG1, IgG2b, and IL-2, IL-4, IL-10, IL-12 in sera of mice immunized with rP-HSP90C (p < 0.05). It was also found LM_W-ASP improved DTH response in HSP90C-injceted mice. More importantly, the mice immunized with rP-HSP90C/LM_W-ASP had fewer CFU (colony forming unites) in the kidneys compared to the mice immunized with rP-HSP90C (p < 0.05). Therefore, LM_W-ASP could be exploited into the novel adjuvant to enhance the efficacy of recombinant protein vaccine.
Water-soluble polysaccharide isolated with alkali from the stem of Physalis alkekengi L.: Structural characterization and immunologic enhancement in DNA vaccine
2015, Carbohydrate Polymers
Citation Excerpt :
Over the past two decades, morbidity and mortality of systemic candidal infection has increased significantly even in the presence of antifungal therapy (Gudlaugsson et al., 2003). Previous findings indicated that fungal heat shock protein 90 (HSP90) plays a key role in protection against systemic Candida albicans (C. albicans) infection (Burnie & Matthews, 2003, 2004; Matthews & Burnie, 1996, 2001, 2005). Consequently, we previously constructed the DNA vaccine (pD-HSP90C) containing epitope C (LKVIRK) of C. albicans HSP90 against systemic candidiasis, and found pD-HSP90C can evoke production of specific antibody against epitope C (LKVIRK) in mice (Yang, Han, Zhao, & Wang, 2014).
A water-soluble polysaccharide (WSPA) was isolated with alkali and purified from the mature stem of Physalis alkekengi L. WSPA (M_w = 31 kDa) was an acid heteropolysaccharide, which consisted of Rha, Ara, Xyl, Gal, Glc and GalA in ratio of 1.0:2.5:0.8:2.7:4.4:1.4. The results from structural analysis indicated backbone and branches of WSPA were composed of (1 → 3)-linked Glc, (1 → 3)-linked Gal, (1 → 2)-linked Xyl, (1 → 2)-linked Ara, and (1 → 2)-linked Rha residues. However, GalA was distributed only in the backbone of WSPA. All branches of WSPA were at O-2 of (1 → 6)-linked Gal and terminated with Glc. More importantly, it was found that WSPA significantly enhanced specific antibody IgG response with higher titers of IgG1 as well as IgG2b (p < 0.05) in mice immunized with DNA vaccine. Therefore, WSPA can be considered as a potential adjuvant candidate in DNA vaccine.
Immunoproteomic profiling of Saccharomyces cerevisiae systemic infection in a murine model
2015, Journal of Proteomics
Citation Excerpt :
Taking into account that S. cerevisiae usually grows at temperatures lower than 37 °C, it is possible that at the first stages of the infection, heat shock proteins are induced for adaptation to the new environmental conditions inside the mouse. Several chaperones have been previously described as immunogenic proteins in different microorganisms [66,67] including C. albicans [38,51,56], and also related to a protective immune response against these pathogens [68,69], as for example, the production of Hsp90 antibodies during candidiasis [70,71]. Comparing the immune responses to D14 and W303 infection, the antibodies against heat shock proteins are present in sera against both strains, but it is apparent that they are much more abundant in serum from D14-infected mice.
Saccharomyces cerevisiae is considered a safe microorganism widely used as a dietary supplement. However, in the latest decades several cases of S. cerevisiae infections have been reported. Recent studies in a murine model of systemic infection have also revealed the virulence of some S. cerevisiae dietary strains. Here we use an immunoproteomic approach based on protein separation by 2D-PAGE followed by Western-blotting to compare the serological response against a virulent dietary and a non-virulent laboratory strains leading to the identification of highly different patterns of antigenic proteins. Thirty-six proteins that elicit a serological response in mice have been identified. Most of them are involved in stress responses and metabolic pathways. Their selectivity as putative biomarkers for S. cerevisiae infections was assessed by testing sera from S. cerevisiae-infected mice against Candida albicans and C. glabrata proteins. Some chaperones and metabolic proteins showed cross-reactivity. We also compare the S. cerevisiae immunodetected proteins with previously described C. albicans antigens. The results point to the stress-related proteins Ahp1, Yhb1 and Oye2, as well as the glutamine synthetase Gln1 and the oxysosterol binding protein Kes1 as putative candidates for being evaluated as biomarkers for diagnostic assays of S. cerevisiae infections.
S. cerevisiae can cause opportunistic infections, and therefore, a precise diagnosis of fungal infections is necessary. This immunoproteomic analysis of sera from a model murine infection with a virulent dietary S. cerevisiae strain has been shown to be a source of candidate proteins for being evaluated as biomarkers to develop assays for diagnosis of S. cerevisiae infections. To our knowledge, this is the first study devoted to the identification of S. cerevisiae immunogenic proteins and the results allowed the proposal of five antigens to be further investigated.
A β-mannan trisaccharide conjugate vaccine aids clearance of Candida albicans in immunocompromised rabbits
2012, Vaccine
Citation Excerpt :
Vaccine strategies to increase host resistance are attracting attention [7–11] because mortality due to Candida infections remains high despite antifungal therapy [12–15]. Experimental and clinical evidence shows the promise of acquired immunity in enhancing host defense mechanisms against the disease and the protective potential of antibody [16–20]. A successful vaccine in combination with antibiotic therapy could provide protection for individuals at high risk; such as patients scheduled to receive abdominal surgery; bone marrow, kidney or heart transplantations, immunosuppressive cancer therapy and those exposed to long-term hospitalization.
A β-(1 → 2)-linked mannose trisaccharide epitope that is the optimal inhibitor of two protective monoclonal antibodies specific for the Candida albicans cell wall phosphomannan was used to create a synthetic conjugate vaccine. Two injections of the trisaccharide-tetanus toxoid conjugate administered with alum induced a robust secondary antibody response in rabbits with trisaccharide specific IgG ELISA titers in excess of 1:100,000. Fluorescent labeling studies demonstrated these antibodies (i) recognized the cell wall β-mannan of C. albicans on hyphae and budding cells and (ii) C. albicans incubated with immune sera bound complement factor C3. The synthetic conjugate vaccine but not the carrier protein, tetanus toxoid reduced Candida load in vaccinated rabbits subsequently rendered leukocytopenic by injection of cyclophosphamide and then challenged with live C. albicans. These data support the contention that antibody mediated immunity plays a role in combating C. albicans infections and suggests that a surprisingly simple, readily accessible synthetic conjugate vaccine may have therapeutic potential.
Anti-Candida antibodies and candidemia in ninety patients with HIV/AIDS and cancer
2007, Journal de Mycologie Medicale
Immunocompromised states such as HIV/AIDS and cancer render the host susceptible to a wide spectrum of infections including fungal infections. The role of humoral immune response in immunity against fungal pathogens such as Candida in immunocompromised individuals such as HIV patients has been questionable owing to the low level or absence of antibodies in these patients. The objective of this study was to analyse the seroprevalence of anti-Candida antibodies in conjunction with occurrence of candidemia in immunocompromised (HIV and cancer) patients. Blood culture was done in biphasic brain heart infusion medium using standard procedures. Anti-Candida IgG was detected using a commercial ELISA kit. 41.43% of HIV and 5% of cancer patients had significant levels of anti-Candida antibodies (>12 U/mL). No episode of candidemia was seen among these patients. However, one episode each of candidemia was observed among HIV and cancer patients who were negative for anti-Candida antibodies. Candidemia did not occur in any of the immunocompromised patients who had significant levels of anti-Candida antibodies. However, it is not possible to conclude from this study whether these antibodies are protective since candidemia occurred rarely in patients who were antibody negative.
Les patients immunocompromis (VIH/sida, cancéreux) sont susceptibles de contracter de nombreuses infections y compris des infections fongiques. Le rôle de la réponse immunitaire dans les mycoses telles que les candidoses chez les patients porteurs du VIH est discutable en raison du bas niveau ou de l’absence d’anticorps chez ces patients. L’objectif de cette étude est d’analyser la prévalence des anticorps anti-Candida en relation avec la survenue d’une candidémie chez des patients immunocompromis (VIH, cancer). Des hémocultures sont réalisées en milieu diphasique cœur-cerveau selon les procédures standards. Les IgG anti-Candida sont détectées à l’aide d’un kit commercial ELISA. 41,43 % des patients VIH et 5 % des patients cancéreux ont des taux significatifs d’anticorps anti-Candida (>12 U/ml). Aucun épisode de candidémie n’a été observé chez ces patients. Toutefois, un épisode de candidémie est observé chez un seul patient VIH et chez un seul patient cancéreux en l’absence d’anticorps anti-Candida. Cette étude ne permet pas de conclure si ces anticorps sont protecteurs étant donné que les candidémies sont rarement observées chez les patients anticorps négatifs.
Protective immune responses against systemic candidiasis mediated by phage-displayed specific epitope of Candida albicans heat shock protein 90 in C57BL/6J mice
2006, Vaccine
Specific epitope (DEPAGE) of Candida albicans heat shock protein 90 (SE-CA-HSP90) was successfully expressed on the surface of filamentous phage fd, fused to the major coat protein pVIII. Protective immune responses mediated by hybrid-phage expressing SE-CA-HSP90 in C57BL/6J mice were evaluated in this paper. The results showed that hybrid-phage particles induced the specific antibody response against SE-CA-HSP90, enhanced delayed-type hypersensitivity (DTH) response, natural killer (NK) cell activity and concanavalin A (ConA)-induced splenocyte proliferation. Furthermore, this study demonstrated that hybrid-phage-immunized mice had fewer colony forming unites (CFU) in the kidneys compared with wild-type phage-immunized mice and TE (1.0 mM EDTA, 0.01M Tris–HCl, pH 8.0)-injected mice and showed statistically significant survival advantage over TE-injected group. In conclusion, the results suggest that the hybrid-phage displaying SE-CA-HSP90 may be considered as a potential candidate for producing vaccines against systemic candidiasis.

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Trends in Microbiology

ReviewAntibodies against Candida: potential therapeutics?

Abstract

J. Immunol. Methods

Trends Microbiol.

Vaccine

Vaccine

FEMS Microbiol. Lett.

Immunol. Today

Biochem. Biophys. Res. Commun.

Comp. Biochem. Physiol.

Med. Hypotheses