Hyr1 Protein and β‐Glucan Conjugates as Anti‐CandidaVaccines

To the Editor—We have read with great interest the recent paper by Luo et al [1] showing that (1) Hyr1p, a known hyphaassociated, glycosyl phosphatidylinositol (GPI)-anchor mannoprotein of the cell wall of Candida albicans [2], confers resistance to neutrophil killing and, in particular, (2) vaccination with a recombinant fragment of this protein is protective against experimental deep-seated candidiasis in mice, likely due to a direct, nonopsonic enhancement of neutrophil killing by anti-Hyr1p antibodies. Of some importance in the assumption by Luo et al [1] that Hyr1p may represent a novel candidate vaccine against candidiasis is our previous demonstration that this protein, together with Als3, another hypha-associated GPI of C. albicans, is a major target recognized by the protective anti-β-glucan antibody 2G8 [3]. This is consequential to the fact that Hyr1p, as other GPIs, in its native form displays a protective, panfungal β-1,3 glucan epitope. We showed that the monoclonal antibody 2G8 exerts protection against experimental systemic and mucosal candidiasis by direct fungus-inhibitory activities that also do not involve opsonophagocytosis [4]. Thus, some GPIs incorporate at least 2 antigenic moieties of great potential interest as subunit vaccines. The first, the protein moiety, specifically carries important virulence functions (such as adhesion and/or, as in the case of Hyr1p, inhibition of neutrophil killing), and the second, which consists of a panfungal saccharide, also plays a role in fungal growth, morphogenesis, and virulence Generating a vaccine from native GPIs could be particularly cumbersome because isolation, purification to high yield, and standardization of such complex and usually polydisperse molecules could be problematic. These problems, however, could be overcome by the use of recombinant proteins or protein fragments, which can be more easily obtained, purified, and standardized. Appropriate formulations of glycoconjugates between these recombinant proteins and the β-glucan saccharide moiety could mimic the native form of the GPI and induce a range of diversified, potent antifungal responses, which could in theory broaden the vaccine targets to include most fungal pathogens in addition to Candida species [5]. There are already examples of highly immunogenic and broadly protective fungal vaccines among the glycoconjugate formulations [4–6].