A. Fattom et al., EFFECT OF CONJUGATION METHODOLOGY, CARRIER PROTEIN, AND ADJUVANTS ON THE IMMUNE-RESPONSE TO STAPHYLOCOCCUS-AUREUS CAPSULAR POLYSACCHARIDES, Vaccine, 13(14), 1995, pp. 1288-1293
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.