Active and passive immunization with rHyr1p-N protects mice against hematogenously disseminated candidiasis.

Abstract

We previously reported that Candida albicans cell surface protein Hyr1 encodes a phagocyte killing resistance factor and active vaccination with a recombinant N-terminus of Hyr1 protein (rHyr1p-N), significantly protects immunocompetent mice from disseminated candidiasis. Here we report the marked efficacy of rHyr1p-N vaccine on improving the survival and reducing the fungal burden of disseminated candidiasis in both immunocompetent and immunocompromised mice using the FDA-approved adjuvant, alum. Importantly, we also show that pooled rabbit anti-Hyr1p polyclonal antibodies raised against 8 different peptide regions of rHyr1p-N protected mice in a hematogenously disseminated candidiasis model, raising the possibility of developing a successful passive immunotherapy strategy to treat this disease. Our data suggest that the rabbit anti-Hyr1p antibodies directly neutralized the Hyr1p virulence function, rather than enhanced opsonophagocytosis for subsequent killing by neutrophil in vitro. Finally, the rHyr1p-N vaccine was protective against non-albicans Candida spp. These preclinical data demonstrate that rHyr1p-N is likely to be a novel target for developing both active and passive immunization strategies against Candida infections.

• Authors: Guanpingsheng Luo, Ashraf S Ibrahim, Samuel W French, John E Edwards Jr, Yue Fu
• Journal: PloS one (PLoS One) Vol. 6 Issue 10 Pg. e25909 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 22028796 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Alum Compounds
• Antibodies, Fungal
• Fungal Proteins
• Fungal Vaccines
• HYR1 protein, Candida albicans
• Peptide Fragments
• Recombinant Proteins
• aluminum sulfate

Topics

• Adjuvants, Immunologic (pharmacology)
• Alum Compounds (pharmacology)
• Amino Acid Sequence
• Animals
• Antibodies, Fungal (immunology)
• Candida albicans (immunology, pathogenicity)
• Candidiasis (prevention & control)
• Cross Reactions (immunology)
• Female
• Fungal Proteins (chemistry)
• Fungal Vaccines (administration & dosage, chemistry, immunology)
• Immunization, Passive (methods)
• Immunocompetence (immunology)
• Immunocompromised Host (immunology)
• Mice
• Mice, Inbred BALB C
• Molecular Sequence Data
• Peptide Fragments (administration & dosage, chemistry, immunology)
• Recombinant Proteins (administration & dosage, chemistry, immunology)
• Survival Rate
• Vaccination (methods)