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PLoS One. 2011;6(10):e25909. doi: 10.1371/journal.pone.0025909. Epub 2011 Oct 10.

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

Author information

1
Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America.

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.

PMID:
22028796
PMCID:
PMC3189951
DOI:
10.1371/journal.pone.0025909
[Indexed for MEDLINE]
Free PMC Article

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