Vaccination with Recombinant Non-transmembrane Domain of Protein Mannosyltransferase 4 Improves Survival during Murine Disseminated Candidiasis.
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.
Center for New Drug Research, School of Pharmacy, Second Military Medical University.
Li
L
Wang
Lan
L
Yan
Xing Xing
XX
Li
Guo Tong
GT
Xu
Mao Mao
MM
An
Yuan Ying
YY
Jiang
D000818:Animals; D002176:Candida albicans / Q000254:growth & development; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology; D002473:Cell Wall; D016207:Cytokines / Q000097:blood; D005260:Female; D005656:Fungal Proteins / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood; D008297:Male; D008364:Mannosyltransferases / Q000276:immunology*; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000276:immunology*; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
D016207:Cytokines; D005656:Fungal Proteins; D007136:Immunoglobulins; D011994:Recombinant Proteins; D014612:Vaccines; D008364:Mannosyltransferases