Active and passive immunization with rHyr1p-N protects mice against hematogenously disseminated candidiasis.
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.
Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America.
Guanpingsheng
G
Luo
Ashraf S
AS
Ibrahim
Samuel W
SW
French
John E
JE
Edwards
Yue
Y
Fu
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000534:Alum Compounds / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology; D002176:Candida albicans / Q000276:immunology / Q000472:pathogenicity; D002177:Candidiasis / Q000517:prevention & control*; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D005656:Fungal Proteins / Q000737:chemistry*; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D007116:Immunization, Passive / Q000379:methods*; D007121:Immunocompetence / Q000276:immunology; D016867:Immunocompromised Host / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D015996:Survival Rate; D014611:Vaccination / Q000379:methods*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000908:Antibodies, Fungal; D005656:Fungal Proteins; D005657:Fungal Vaccines; C101636:HYR1 protein, Candida albicans; D010446:Peptide Fragments; D011994:Recombinant Proteins; C041524:aluminum sulfate