EFFECT OF CONJUGATION METHODOLOGY, CARRIER PROTEIN, AND ADJUVANTS ON THE IMMUNE-RESPONSE TO STAPHYLOCOCCUS-AUREUS CAPSULAR POLYSACCHARIDES

Conjugate vaccines were prepared with S. aureus type 8 capsular polysa ccharide (CP) using three carrier proteins: Pseudomonas aeruginosa exo toxin A (ETA), a non-toxic recombinant ETA (rEPA), and diphtheria toro id (DTd). Adipic acid dihydrazide (ADH) or N-succinimidyl 3-(2-pyridyl dithio) propionate (SPDP) was used as a spacer to link the CP to carri er protein All conjugates gave a high immune response with a boost aft er the second immunization. Conjugates prepared with ADH gave higher a ntibody titers than conjugates prepared with SPDP. IgG(1) was the prim ary subclass elicited by all conjugates regardless of the carrier prot ein or the conjugation method used to prepare the vaccines. The non-im munogenic CP and the conjugates were formulated with either monophosph oryl lipid A (MPL), QS21, or in Novasomes(TM) and evaluated in mice. W hile the adjuvants failed to improve the immunogenicity of the nonconj ugated CP, a more than fivefold increase in the antibody levels was ob served when these adjuvants were used with the conjugates. Significant rises in IgG(2b) and IgG(3) were observed with all formulations. The enhancement of the immunogenicity and the IgG subclass shift, as seen with some adjuvants, may prove to be important in immunocompromised pa tients.