The effect of conjugation on immunogenicity and potency of protein carriers of polyribosylribitol phosphate (PRP) conjugated vaccines in the mouse model

Abstract

Immunogenicity and vaccine potency of carrier proteins of two different PRP-tetanus toxoid (PRP-T) conjugated vaccines, produced using different size PRP (Act-Hib & Amvax Hib-T), and one PRP-CRM197 (Hib-TITER) were studied. The immunogenicity and the vaccine potency of the carrier component of the tested PRP-conjugated vaccines, and their influences on the potency of the tetanus toxoid (T) and of the diphtheria toxoid (D) component of diphtheria toxoid-tetanus toxoid-acellular pertussis-inactivated polio vaccine (DTaP-IPV) were variable. The T component of Act-Hib (large size PRP) was as immunogenic and potent as the T component of the DTaP-IPV vaccine, and a combination of Act-Hib and DTaP-IPV resulted in a more than five-fold increase in the potency of the T However, Amvax Hib-T (small size PRP) did not show any anti-T response on its own, and a combination of Amvax Hib-T and DTaP-IPV did not affect the T potency of the DTaP-IPV vaccine. In immunogenicity studies with multiple shots, Hib-TITER (small size PRP) produced significantly less anti-D antibodies than non-conjugated D. Hib-TITER did not show any D potency on its own, while a combination of a Hib-TITER and DTaP-IPV increased the potency of the D component of DTaP-IPV vaccine significantly. Thus, in the case of a combination of T-and D-containing vaccines with a PRP-conjugated vaccine in which either T or CRMI 97 has been used as the carrier, the influence of these carriers on basic immunogenicity and vaccine potency of T and D, respectively, should be considered carefully. We propose the techniques employed in this study for the quality control of combined vaccines consisting of diphtheria, tetanus, and PRP-conjugated vaccines.