Effect of Branched α‐Oligomannoside Structures on Induction of Anti‐Candida Humoral Immune Response

Abstract

Several studies have established the potential efficacy of humoral immunity, primarily mannan-specific antibodies, in host protection against major fungal pathogen Candida albicans. In this study, we analysed humoral immune response induced by immunization with BSA-based conjugates bearing synthetic a-1, 6-branched oligomannosides (pentamannosides (M5) or hexamannosides (M6)) mimicking antigenic sequences of Candida cell wall mannan. We analysed the ability of antibodies prepared by immunization to recognize relevant antigenic determinants in mannan polysaccharide structure and in C. albicans yeast and hyphal morphoforms. M6-BSA conjugate induced markedly higher levels of mannan-specific IgG compared with M5-BSA conjugate. In contrast to M5-BSA conjugate, M6-BSA conjugate induced immunoglobulin isotype class switch from IgM to IgG, as revealed also from ELISPOT analysis. Immunizationinduced antibodies showed higher reactivity with hyphal form of C. albicans cells. The reduced immunogenicity of M5-BSA conjugate seems to be related to branching point location at terminal non-reducing end in comparison with M6-BSA oligomannoside with branching point at non-terminal location. Candidacidal activity assay revealed different capacity of sera prepared by immunization with M5-BSA and M6-BSA conjugates to improve candidacidal activity of polymorphonuclear leucocytes. Limited capacity of a-1,6-branched oligomannoside -BSA conjugates to induce antibodies significantly enhancing candidacidal activity of polymorphonuclear leucocytes -was presumably related to absence of antibodies with strong reactivity to corresponding antigenic determinants in natural cell wall mannan and with reduced ability to activate complement. The study documented markedly structure-dependent immunogenicity and limited capacity of branched a-mannooligosides conjugates to induce production of potentially protective antibodies.

Synthetically prepared glycooligosaccharides mimickingCandida albicanscell wall glycan antigens - novel tools to study host-pathogen interactions

“…In addition, our previously published studies revealed structure‐dependent immunogenicity of synthetic oligomannoside–BSA conjugates and capability of vaccination‐induced polyclonal sera to improve candidacidal activity of leucocytes (Paulovičová et al ., ) and polymorphonuclear leucocytes (Paulovičová et al ., , ) in vitro . Results obtained with branched oligomannoside–BSA conjugates (M5‐1, M5‐2 and M6) revealed a lower ability to induce antibodies, significantly enhancing candidacidal activity in comparison with linear oligomannoside–BSA conjugates (M2 and M7‐A; Paulovičová et al ., , , , ).…”

How Can Elispot Add Information to Improve Knowledge on Tropical Diseases?

“…M6-BSA conjugate induced markedly higher levels of mannan-specific IgG compared to the M5-BSA conjugate. In contrast to the M5-BSA conjugate, the M6-BSA conjugate induced immunoglobulin isotype class switch from IgM to IgG, as revealed also from Elispot analysis [ 115 ].…”

Immunological basis of anti‐Candida vaccines focused on synthetically prepared cell wall mannan‐derived manno‐oligomers

“…The tested fungal vaccines have a wide range of compositions ranging from whole fungal cells and inactivated organisms to subcellular vaccines based on Candida cell wall mannan , synthetically prepared oligomannosides conjugated to carrier protein or oligomannoside conjugated to single recombinant peptide fragment . Advanced trends in prophylactic and therapeutic possibilities for fungal infections are directed to development of subunit vaccines composed from single specific and immunologically active cell wall‐derived antigens.…”

“…Despite the presumption that α‐1,2 linked oligomannosides represent epitopes that induce non‐protective antibodies, several glycoconjugates based on synthetically prepared α‐1,2 linked oligomannosides (Table ) have been prepared and their immunomodulatory properties analyzed . It has been shown that these prepared conjugates are able to stimulate cytokine production of splenocytes in vitro and induce a specific antibody response in vivo .…”

“…Antibodies induced by different manno‐oligosaccharide‐based conjugates differ significantly in their ability to react with native cell wall mannan of intact C. albicans cells and the induced antibodies react with different intensities towards C. albicans cells in yeast and hyphal growth form . According to antigenic differences in dimorphic yeast C. albicans mannan , several tested glycoconjugates induce production of antibodies with greater specificity for the hyphal growth form .…”