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.
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.
Fattom
A
A
Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Cancer Institute, Bethesda, Maryland 20892.
Schneerson
R
R
Watson
D C
DC
Karakawa
W W
WW
Fitzgerald
D
D
Pastan
I
I
Li
X
X
Shiloach
J
J
Bryla
D A
DA
Robbins
J B
JB
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
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