EPITOPIC OVERLOAD AT THE SITE OF INJECTION MAY RESULT IN SUPPRESSION OF THE IMMUNE-RESPONSE TO COMBINED CAPSULAR POLYSACCHARIDE CONJUGATE VACCINES

Capsular polysaccharide (CP) conjugate vaccines targeting a variety of bacterial infections are currently under development and clinical eva luation. The inclusion of multiple CP serotypes combined in a single i njection is an important maneuver being evaluated. The combination of CP conjugate vaccines into a single multivalent injection may result i n competition among the different components and adversely affect the immunogenicity of any individual conjugate. We observed a reduction of 30-90% in antibody responses to several serotypes in mice when immuno genicity of a 12-valent Escherichia coil (E. coli) lipopolysaccharide (LPS) conjugate vaccine was compared to the immunogenicity of each mon ovalent vaccine evaluated separately. A reduction of 30% was observed in the Staphylococcus aureus (S. aureus) type 8 CP antibodies when a t ype 8-rEPA conjugate was combined with a type 5-rEPA conjugate. S. aur eus types 5 and 8-rEPA conjugates were combined with 100 mu g of eithe r rEPA (homologous) or diphtheria toroid (DT) (heterologous) carrier p roteins, and evaluated in rEPA or DT primed mice. The addition of the homologous protein resulted in a 64% reduction in type 5 CP antibodies . The heterologous protein did not affect the immunogenicity of the ty pe 5. We postulate that the free protein competed with the conjugate a nd recruited most of the rEPA primed T cells. In the case of the DT co njugates, the DT targeted different populations of the T cells, thus i nterference was not observed. These data suggested that the epitopic l oad rather than the antigenic load at the site of injection caused red uced immunogenicity of the conjugates. We theorize that individual com ponents of multivalent CP vaccines conjugated to the same carrier prot eins would compete for a limited number of specific carrier protein pr imed T cells. This would result in one or more components being unavai lable in eliciting a sufficient immune response. The use of multiple c arrier proteins should be considered as an approach to reduce interfer ence when multivalent conjugate vaccines are to be formulated into a s ingle injection. (C) 1998 Elsevier Science Ltd. All rights reserved.