title: Laboratory and clinical evaluation of conjugate vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides bound to Pseudomonas aeruginosa recombinant exoprotein A.
abstract: The synthesis, standardization, and immunogenicity in young outbred mice and clinical evaluation in adult volunteers of investigational vaccines designed to induce serum antibodies to the type 5 and type 8 capsular polysaccharides (CPs) of Staphylococcus aureus are described. Conjugates composed of the type 5 CP and a sonicated preparation of a high-molecular-weight type 8 CP bound to a nontoxic recombinant protein derived from Pseudomonas aeruginosa exotoxin A (rEPA) were synthesized. The conjugates were nontoxic and elicited serum CP antibodies after two subcutaneous injections into young outbred mice; a third injection elicited a booster response. The lower-molecular-weight type 8 CP was not immunogenic in the mice, and the high-molecular-weight type 8 CP elicited low levels of antibodies without a booster effect. In the volunteers, neither the conjugates nor the type 8 CP alone caused significant local reactions or fever. The conjugates elicited type-specific antibodies of both the immunoglobulin M (IgM) and IgG classes after the first injection; a second injection 6 weeks later did not stimulate a booster effect. The high-molecular-weight type 8 CP alone, injected once only, elicited levels of IgG and IgM type-specific antibodies similar to those of the conjugate. The vaccine-induced CP antibodies were mostly of the IgG1 and IgG2 subclasses and had opsonophagocytic activity. The conjugates elicited IgG antibodies to the native exotoxin A with neutralizing activity. In summary, the type 5 and type 8 conjugates were safe and elicited biologically active antibodies to both the CP and rEPA components.
authors.affiliation: Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: A
authors.initials: A
authors.lastname: Fattom
authors.forename: R
authors.initials: R
authors.lastname: Schneerson
authors.forename: D C
authors.initials: DC
authors.lastname: Watson
authors.forename: W W
authors.initials: WW
authors.lastname: Karakawa
authors.forename: D
authors.initials: D
authors.lastname: Fitzgerald
authors.forename: I
authors.initials: I
authors.lastname: Pastan
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Shiloach
authors.forename: D A
authors.initials: DA
authors.lastname: Bryla
authors.forename: J B
authors.initials: JB
authors.lastname: Robbins
mesh_terms: D036002:ADP Ribose Transferases; D000328:Adult; D000818:Animals; D016667:Bacterial Capsules / Q000276:immunology*; D001427:Bacterial Toxins; D001428:Bacterial Vaccines / Q000276:immunology* / Q000633:toxicity; D001770:Blood Bactericidal Activity; D005069:Evaluation Studies as Topic; D005098:Exotoxins / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology* / Q000633:toxicity; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D005098:Exotoxins; D011135:Polysaccharides, Bacterial; D014614:Vaccines, Synthetic; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A