Synthesis and immunologic properties in mice of vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides conjugated to Pseudomonas aeruginosa exotoxin A.
Epidemiological, serological and in vitro phagocytosis experiments provide evidence that the newly discovered type 5 and type 8 capsular polysaccharides (CPs) are both virulence factors and protective antigens for bacteremia caused by Staphylococcus aureus. Neither type 5 nor type 8 CP elicited serum antibodies when injected into mice. These two CPs were bound to Pseudomonas aeruginosa exotoxin A (ETA) to form conjugates by using the synthetic scheme devised for the CP (Vi) of Salmonella typhi and of pneumococcus type 12F (A. Fattom, W. F. Vann, S. C. Szu, A. Sutton, X. Li, D. Bryla, G. Schiffman, J. B. Robbins, and R. Schneerson, Infect. Immun. 56:2292-2298, 1988; S. C. Szu, A. L. Stone, J. D. Robbins, R. Schneerson, and J. B. Robbins, J. Exp. Med. 166:1510-1524, 1987). Both S. aureus CP-ETA conjugates elicited a rise in CP antibodies. As components of conjugates, both S. aureus CPs acquired T-cell-dependent properties, as shown by their ability to respond to carrier priming and to stimulate booster responses. The conjugate-induced antibodies facilitated type-specific opsonization of S. aureus by human polymorphonuclear leukocytes. The conjugates also induced ETA antibodies which neutralized the native toxin in vitro. Clinical studies of these two conjugates for active or passive immunization of patients at risk for S. aureus bacteremia are planned.
Fattom
A
A
National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Schneerson
R
R
Szu
S C
SC
Vann
W F
WF
Shiloach
J
J
Karakawa
W W
WW
Robbins
J B
JB
D036002:ADP Ribose Transferases; D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000502:physiology; D016667:Bacterial Capsules; D001427:Bacterial Toxins / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology* / Q000633:toxicity; D002240:Carbohydrate Sequence; D003432:Cross-Linking Reagents; D005098:Exotoxins / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010587:Phagocytosis / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology / Q000633:toxicity; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D003432:Cross-Linking Reagents; D005098:Exotoxins; D011135:Polysaccharides, Bacterial; D014614:Vaccines, Synthetic; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C054106:capsular polysaccharide, type 5, Staphylococcus aureus; C064836:capsular polysaccharide, type 8, Staphylococcus aureus