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Infect. Immun. doi:10.1128/IAI.00700-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The anti-fungal rAls3p-N vaccine protects mice against the bacterium Staphylococcus aureus

The Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, 1124 West Carson St., Torrance CA 90502; The David Geffen School of Medicine at UCLA; Department of Biology, Brooklyn College of City University of New York, Brooklyn, NY 11210

^* To whom correspondence should be addressed. Email: bspellberg{at}labiomed.org.

	Abstract

Vaccination with the recombinant N-terminus of the candidal adhesin, Als3p (rAls3p-N), protects mice from lethal candidemia. Candidal Als3p is also structurally similar to the Microbial Surface Components Recognizing Adhesive Matrix Molecule (MSCRAMM) adhesin, clumping factor (ClfA), 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 survival of vaccinated mice subsequently infected with multiple clinical isolates of S. aureus, including methicillin-resistant (MRSA) strains. The rAls3p-N 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. 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 40,000-50,000 deaths annually in the United States alone.