title: Protein antigens increase the protective efficacy of a capsule-based vaccine against Staphylococcus aureus in a rat model of osteomyelitis.
abstract: Staphylococcus aureus is an invasive bacterial pathogen, and antibiotic resistance has impeded adequate control of infections caused by this microbe. Moreover, efforts to prevent human infections with single-component S. aureus vaccines have failed. In this study, we evaluated the protective efficacy in rats of vaccines containing both S. aureus capsular polysaccharides (CPs) and proteins. The serotypes 5 CP (CP5) and 8 CP (CP8) were conjugated to tetanus toxoid and administered to rats alone or together with domain A of clumping factor A (ClfA) or genetically detoxified alpha-toxin (dHla). The vaccines were delivered according to a preventive or a therapeutic regimen, and their protective efficacy was evaluated in a rat model of osteomyelitis. Addition of dHla (but not ClfA) to the CP5 or CP8 vaccine induced reductions in bacterial load and bone morphological changes compared with immunization with either conjugate vaccine alone. Both the prophylactic and therapeutic regimens were protective. Immunization with dHla together with a pneumococcal conjugate vaccine used as a control did not reduce staphylococcal osteomyelitis. The emergence of unencapsulated or small-colony variants during infection was negligible and similar for all of the vaccine groups. In conclusion, addition of dHla to a CP5 or CP8 conjugate vaccine enhanced its efficacy against S. aureus osteomyelitis, indicating that the inclusion of multiple antigens will likely enhance the efficacy of vaccines against both chronic and acute forms of staphylococcal disease.
authors.affiliation: Instituto de Microbiología y Parasitología Médica (IMPaM), Universidad de Buenos Aires and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Santiago M
authors.initials: SM
authors.lastname: Lattar
authors.forename: Mariángeles
authors.initials: M
authors.lastname: Noto Llana
authors.forename: Philippe
authors.initials: P
authors.lastname: Denoël
authors.forename: Sophie
authors.initials: S
authors.lastname: Germain
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Buzzola
authors.forename: Jean C
authors.initials: JC
authors.lastname: Lee
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Sordelli
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D010019:Osteomyelitis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D013209:Staphylococcal Vaccines; D018074:Vaccines, Conjugate