Vaccination with Recombinant Non-transmembrane Domain of Protein Mannosyltransferase 4 Improves Survival during Murine Disseminated Candidiasis

Abstract

Candida albicans is the most common cause of invasive fungal infections in humans. The C. albicans cell wall proteins play an important role in crucial host-fungus interactions and might be ideal vaccine targets to induce protective immune response in host. Meanwhile, protein that is specific to C. albicans is also an ideal target of vaccine. In this study, 11 proteins involving cell wall biosynthesis, yeast-to-hypha formation, or specific to C. albicans were chosen and were successfully cloned, purified and verified. The immune protection of vaccination with each recombinant protein respectively in preventing systemic candidiasis in BALB/c mice was assessed. The injection of rPmt4p vaccination significantly increased survival rate, decreased fungal burdens in the heart, liver, brain, and kidneys, and increased serum levels of both immunoglobulin G (IgG) and IgM against rPmt4p in the immunized mice. Histopathological assessment demonstrated that rPmt4p vaccination protected the tissue structure, and decreased the infiltration of inflammatory cells. Passive transfer of the rPmt4p immunized serum increased survival rate against murine systemic candidiasis and significantly reduced organ fungal burden. The immune serum enhanced mouse neutrophil killing activity by directly neutralizing rPmt4p effects in vitro. Levels of interleukin (IL)-4, IL-10, IL-12p70, IL-17A and tumor necrosis factor (TNF)-α in serum were higher in the immunized mice compared to those in the adjuvant control group. In conclusion, our results suggested that rPmt4p vaccination may be considered as a potential vaccine candidate against systemic candidiasis.

The prophylactic effects of monoclonal antibodies targeting the cell wall Pmt4 protein epitopes of Candida albicans in a murine model of invasive candidiasis

“…Protein mannosyltransferase 4 represents one of the PMT gene family localized to the C. albicans cell wall; it encodes five isoforms of protein mannosyltransferases, which initiates O-mannosylation of secretory proteins, and is essential for the maintenance of hyphal growth, virulence, and cell wall composition (Prill et al, 2005). Previously, we have confirmed that rPmt4p vaccination improves the survival rate in a murine model of disseminated candidiasis and can serve as a vaccine candidate against systemic candidiasis (Wang et al, 2015a). Herein, we prepared anti-rPmt4p mAbs to investigate whether these mAbs protected mice against disseminated candidiasis and examined the potential protective mechanisms.…”

“…In our previous study, vaccination with the recombinant mannosyltransferase 4 (rPmt4p) exhibited a significant protective effect in mice with invasive C. albicans infection. Specifically, the rPmt4p vaccine reduced mortality rate and activated both humoral and cellular immune responses ( Wang et al, 2015a ).…”