title: Immune response and functional role of antibodies raised in heifers against a Staphylococcus aureus CP5 lysate and recombinant antigens vaccine formulated with Iscom Matrix adjuvant.
abstract: Staphylococcus aureus is the most frequently isolated pathogen from bovine intramammary infections worldwide. Commercially available vaccines for mastitis control are composed either of S. aureus lysates or inactivated whole-cells formulated with traditional adjuvants. We recently showed the ability of a S. aureus CP5 lysate vaccine adjuvanted with Iscom Matrix to generate a longer lasting specific antibody response in blood and milk, with improved opsonic capacity, compared with a S. aureus CP5 whole-cell formulation. The aim of the present study was to obtain an experimental immunogen composed of lysed cells of a CP5 S. aureus strain supplemented with recombinant clumping factor A, fibronectin binding protein A and β-toxin formulated with Iscom Matrix, characterize the immune response generated when immunizing pregnant heifers and assess the functional role of antibodies raised against this immunogen in experimental models. Both a lysate vaccine and a lysate+recombinant antigens vaccine elicited antibodies that promoted neutrophil phagocytosis and inhibited internalization into mammary epithelial cells, in vitro. Incorporation of defined antigenic molecules to the lysate formulation elicited a strong specific humoral immune response against both lysate and recombinant antigens and was associated with higher expression of regulatory and pro-inflammatory cytokines. In addition, antibodies were efficient for blocking S. aureus binding to bovine fibrinogen and fibronectin, and neutralizing β-toxin effect in vitro, placing these antigens as candidates to be included in a formulation directed to prevent staphylococcal bovine mastitis.
authors.affiliation: Estación Experimental Agropecuaria Rafaela, INTA, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.
authors.forename: C M
authors.initials: CM
authors.lastname: Camussone
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina; Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: N
authors.initials: N
authors.lastname: Pujato
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina; Facultad de Ciencias Veterinarias, Universidad Nacional del Litoral, Esperanza, Santa Fe, Argentina.
authors.forename: M S
authors.initials: MS
authors.lastname: Renna
authors.affiliation: Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: C M
authors.initials: CM
authors.lastname: Veaute
authors.affiliation: Department of Clinical Virology, Uppsala University, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Morein
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina; Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: I S
authors.initials: IS
authors.lastname: Marcipar
authors.affiliation: Estación Experimental Agropecuaria Rafaela, INTA, Santa Fe, Argentina; Facultad de Ciencias Veterinarias, Universidad Nacional del Litoral, Esperanza, Santa Fe, Argentina. Electronic address: calvinho.luis@inta.gob.ar.
authors.forename: L F
authors.initials: LF
authors.lastname: Calvinho
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D002417:Cattle; D002460:Cell Line; D003030:Coagulase / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000097:blood; D005260:Female; D006460:Hemolysin Proteins / Q000235:genetics / Q000276:immunology; D016882:ISCOMs / Q000494:pharmacology; D007114:Immunization / Q000379:methods / Q000662:veterinary*; D008414:Mastitis, Bovine / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D008892:Milk / Q000382:microbiology; D011247:Pregnancy; D011897:Random Allocation; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018709:Statistics, Nonparametric; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology* / Q000592:standards
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D016207:Cytokines; D006460:Hemolysin Proteins; D016882:ISCOMs; D013209:Staphylococcal Vaccines; D014614:Vaccines, Synthetic; C078635:fibronectin-binding proteins, bacterial; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus
keywords: Bovine mastitis; Immunization; Iscom Matrix; Lysate; Recombinant antigens; Staphylococcus aureus