Antifungal Vaccine Derived from the Recombinant N Terminus of Als3p Protects Mice against the Bacterium Staphylococcus aureus

• Published in: Infection and Immunity 2008-10, Vol.76 (10), p.4574-4580
• Main Authors: Spellberg, Brad, Ibrahim, Ashraf S, Yeaman, Michael R, Lin, Lin, Fu, Yue, Avanesian, Valentina, Bayer, Arnold S, Filler, Scott G, Lipke, Peter, Otoo, Henry, Edwards, John E. Jr
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Adoptive Transfer; Aluminum Hydroxide - administration & dosage; Aluminum Hydroxide - pharmacology; Animals; Applied microbiology; B-Lymphocytes - immunology; Bacteremia - microbiology; Bacteriology; Biological and medical sciences; Candida; Coagulase - immunology; Colony Count, Microbial; Cross Reactions; Fundamental and applied biological sciences. Psychology; Fungal Proteins - genetics; Fungal Proteins - immunology; Fungal Vaccines - immunology; Immunization, Passive; Mice; Mice, Inbred BALB C; Microbial Immunity and Vaccines; Microbiology; Miscellaneous; Staphylococcal Infections - prevention & control; Staphylococcus aureus; Survival Analysis; T-Lymphocytes - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00700-08

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.