Protective immune responses to a multi-gene DNA vaccine against Staphylococcus aureus.
To investigate the strategy of using a multivalent polyprotein DNA vaccine against Staphylococcus aureus, a series of plasmids was used to immunize mice followed by infectious challenge. The plasmid vaccines expressed Clumping factor A (Clfa), fibronectin binding protein A (FnBPA) and the enzyme Sortase (Srt) as single proteins or combined as a polyprotein. All animals produced a mixed Th1 and Th2 response including functional antigen-specific, mostly IgG2a antibodies, sustained production of IFN-gamma and a predominantly CD8+ T-cell response. Upon challenge with a virulent S. aureus isolate (Sa042), after 21 days, 55% of the multi-gene vaccinated mice survived infection compared to only 15% of the control groups. Vaccinated mice showed no signs of arthritis when challenged with the less virulent "Newman" strain that caused reactive arthritis in the controls. The results suggest that a multi-gene polyprotein-expressing nucleic acid vaccine alone produces a combined Th1 and Th2 response that can contribute to protection against the complex pathogenesis of S. aureus.
Gaudreau
Marie-Claude
MC
Centre d'Etude et de Valorisation de la Diversité Microbienne, Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada J1K 2R1.
Lacasse
Pierre
P
Talbot
Brian G
BG
D018829:Adhesins, Bacterial / Q000235:genetics*; D019881:Aminoacyltransferases / Q000235:genetics*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000918:Antibody Specificity; D001426:Bacterial Proteins / Q000235:genetics*; D003030:Coagulase / Q000235:genetics*; D003546:Cysteine Endopeptidases / Q000235:genetics*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D013209:Staphylococcal Vaccines / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D007074:Immunoglobulin G; D013209:Staphylococcal Vaccines; D019444:Vaccines, DNA; C078635:fibronectin-binding proteins, bacterial; D007371:Interferon-gamma; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases