title: The antifungal vaccine derived from the recombinant N terminus of Als3p protects mice against the bacterium Staphylococcus aureus.
abstract: Vaccination with the recombinant N terminus of the candidal adhesin Als3p (rAls3p-N) protects mice from lethal candidemia. Candidal Als3p also is structurally similar to the microbial surface components recognizing adhesive matrix molecule adhesin, clumping factor, from Staphylococcus aureus. To determine the potential for cross-kingdom vaccination, we immunized mice with rAls3p-N or negative control proteins and challenged them via the tail vein with S. aureus or other gram-positive or gram-negative pathogens. The rAls3p-N vaccine, but neither tetanus toxoid nor a related Als protein (Als5p), improved the survival of vaccinated mice subsequently infected with multiple clinical isolates of S. aureus, including methicillin-resistant strains. The rAls3p-N vaccine was effective against S. aureus when combined with aluminum hydroxide adjuvant. However, the vaccine did not improve the survival of mice infected with other bacterial pathogens. Vaccinated, infected mice mounted moderated type 1 immune responses. T lymphocyte-deficient mice were more susceptible to S. aureus infection, but B lymphocyte-deficient mice were not. Furthermore, T but not B lymphocytes from vaccinated mice mediated protection in adoptive transfer studies. The passive transfer of immune serum was not protective. These data provide the foundation for cross-kingdom vaccine development against S. aureus and Candida, which collectively cause 200,000 bloodstream infections resulting in >/=40,000 to 50,000 deaths annually in the United States alone.
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor, University of California at Los Angeles Medical Center, Torrance, California 90502, USA. bspellberg@labiomed.org
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Ibrahim
authors.forename: Michael R
authors.initials: MR
authors.lastname: Yeaman
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Yue
authors.initials: Y
authors.lastname: Fu
authors.forename: Valentina
authors.initials: V
authors.lastname: Avanesian
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Bayer
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.forename: Peter
authors.initials: P
authors.lastname: Lipke
authors.forename: Henry
authors.initials: H
authors.lastname: Otoo
authors.forename: John E
authors.initials: JE
authors.lastname: Edwards
mesh_terms: D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D016470:Bacteremia / Q000382:microbiology; D003030:Coagulase / Q000276:immunology; D015169:Colony Count, Microbial; D003429:Cross Reactions; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology*; D005657:Fungal Vaccines / Q000276:immunology*; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D013203:Staphylococcal Infections / Q000517:prevention & control*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: C113620:ALS3 protein, Candida albicans; D000276:Adjuvants, Immunologic; D003030:Coagulase; D005656:Fungal Proteins; D005657:Fungal Vaccines; D014614:Vaccines, Synthetic; D000536:Aluminum Hydroxide