Abstract
Systemic candidiasis is an invasive fungal infection caused by members of the genus Candida. The recent emergence of antifungal drug resistance and increased incidences of infections caused by non-albicans Candida species merit the need for developing immune therapies against Candida infections. Although the role of cellular immune responses in anti-Candida immunity is well established, less is known about the role of humoral immunity against systemic candidiasis. This review summarizes currently available information on humoral immune responses induced by several promising Candida vaccine candidates, which have been identified in the past few decades. The protective antibody and B-cell responses generated by polysaccharide antigens such as mannan, β-glucan, and laminarin, as well as protein antigens like agglutinin-like sequence gene (Als3), secreted aspartyl proteinase (Sap2), heat shock protein (Hsp90), hyphally-regulated protein (Hyr1), hyphal wall protein (Hwp1), enolase (Eno), phospholipase (PLB), pyruvate kinase (Pk), fructose bisphosphate aldolase (Fba1), superoxide dismutase gene (Sod5) and malate dehydrogenase (Mdh1), are outlined. As per studies reviewed, antibodies induced in response to leading Candida vaccine candidates contribute to protection against systemic candidiasis by utilizing a variety of mechanisms such as opsonization, complement fixation, neutralization, biofilm inhibition, direct candidacidal activity, etc. The contributions of B-cells in controlling fungal infections are also discussed. Promising results using anti-Candida monoclonal antibodies for passive antibody therapy reinforces the need for developing antibody-based therapeutics including anti-idiotypic antibodies, single-chain variable fragments, peptide mimotopes, and antibody-derived peptides. Future research involving combinatorial immunotherapies using humanized monoclonal antibodies along with antifungal drugs/cytokines may prove beneficial for treating invasive fungal infections.
Highlights
Monocyte deficient mice are more susceptible to infections with C. albicans [21], and monocytes exposed to C. albicans produce tumor necrosis factor-α (TNF-α), which is required for surviving systemic candidiasis [22]
Generation of innate and adaptive immune responses are essential for fungal clearance and the major players of innate and adaptive immunity include phagocytes, cytokines, complement proteins, T-cells, B-cells, and antibodies
Several Candida virulence antigens, like cell wall polysaccharides, surface proteins, and enzymes have been investigated as vaccine candidates to assess the protective immune responses against fungal challenge in animal models of systemic candidiasis
Summary
Candidiasis broadly refers to fungal infections caused by members of the genus Candida. According to the Centers for Disease Control and Prevention (CDC), the mortality attributed to systemic candidiasis is around 40%–70% worldwide, even with the use of antifungal therapies [3]. It is the fourth most common nosocomial bloodstream infection, which affects intensive care unit patients [4]. The emergence of antifungal drug resistance in Candida species has been increasing over the past decade and multidrug-resistant mechanisms to Candida species pose a serious threat to public health worldwide. Recent advances regarding monoclonal antibodies and their mechanisms of protection, anti-idiotypic antibodies, single-chain variable fragments, and peptide mimotopes are discussed, which may be useful for the development of direct antibody-based, as well as combination immunotherapies against invasive candidiasis
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