Related Experiment Videos
Non-interference between two protein carriers when used with the same polysaccharide for pneumococcal conjugate
Porter Anderson1, John Treanor, Susan Porcelli
1Department of Microbiology/Immunology, Elmwood Pediatric Group, University of Rochester Medical Center, 601 Elmwood Avenue, P.O. Box 672, NY 14642, USA.
Insights
This study compared tetanus toxoid (T) and diphtheria CRM-197 (C) carriers in conjugate vaccines for children. Results showed no consistent carrier difference; immunogenicity varied by polysaccharide serotype, suggesting future vaccine strategies should consider this.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Conjugate vaccines link polysaccharides (PS) to carrier proteins to enhance immunogenicity.
- Tetanus toxoid (T) and diphtheria CRM-197 (C) are common carriers, but their comparative efficacy needs further study.
- Understanding carrier-specific immune responses is crucial for developing effective multivalent vaccines.
Purpose of the Study:
- To compare the safety and immunogenicity of tetanus toxoid (T) and diphtheria CRM-197 (C) as carriers in tetravalent conjugate vaccines.
- To evaluate the immune response in 2-year-old children receiving vaccines with either T or C carriers, or a mixture of both.
- To assess potential interference or synergy when using a combination of T and C carriers.
Main Methods:
- Tetravalent conjugate vaccines were prepared using identical coupling chemistry and polysaccharide loading for PS types 6A, 14, 19F, and 23F with T or C carriers.
- Two-year-old children received primary and secondary injections of either T-based, C-based, or a mixture of T and C vaccines.
- Serum IgG antibody responses to the four PS types were measured by ELISA before and after vaccination.
Main Results:
- No consistent significant difference in immunogenicity was observed between T and C carriers across all PS types.
- Specific serotypes showed differential responses, with C-based vaccines performing better for 19F and 23F post-primary and post-secondary immunization, respectively.
- The T/C mixture vaccine showed no negative interference and comparable or enhanced responses for certain serotypes (19F, 23F) compared to the T-only vaccine.
Conclusions:
- The choice of carrier (T or C) did not consistently determine immunogenicity; responses were serotype-dependent.
- Combining T and C carriers at halved doses did not result in negative interference and may offer advantages for specific serotypes.
- Future multivalent conjugate vaccine development could benefit from strategies that reduce carrier dosage and leverage dual-carrier T-helper cell recruitment.
Abstract:
The carriers tetanus toxoid (T) and diphtheria CRM-197 (C) were compared in conjugate vaccines using identical coupling chemistry and polysaccharide (PS) loading, for safety and immunogenicity in 2-year-old children. Also tested were a mixture of halved doses of both carriers bearing the same PS serotypes. For this study, PS types 6A, 14, 19F, and 23F (separately) were coupled to T or C by reductive amination at PS/protein ratios of 0.50+/-0.18. With each carrier the four PS types were combined, giving the tetravalent vaccines "T-6, -14, -19, -23" or "C-6, -14, -19, -23" containing 50 microg of the carrier and roughly 20 microg total PS per ml of saline (no adjuvant). The children received primary (1') injections of 50 microg (protein) of either vaccine or a mixture of 25 microg of both; identical secondary (2') injections were given 2 months afterwards. Sera were taken before the 1' and 2' and 1 month post-2', and serum IgG responses to the four PS were determined by ELISA. For geometric mean (GM) post-1' antibody, "C-6, -14, -19, -23" exceeded "T-6, -14, -19, -23" for type 19F; for 2' antibody, "T-6, -14, -19, -23" exceeded "C-6, -14, -19, -23" for type 14, but "C-6, -14, -19, -23" and the T/C mixture exceeded "T-6, -14, -19, -23" for the type 23F response. No other differences were significant. Analyzed by individual fold-rises, "C-6, -14, -19, -23" and the T/C mixture exceeded "T-6, -14, -19, -23" for types 19F and 23F. Thus, there was no consistent difference between the T and C carriers; rather, the results differed by serotype. When a mixture of halved doses of "T-6, -14, -19, -23" and "C-6, -14, -19, -23" was injected, neither negative nor positive interference with the PS antibody responses was found. Anticipating multivalent PS conjugate vaccines of the future to be used in infancy, this strategy would have two hypothetical advantages worth further investigation-avoiding "carrier epitopic overload" by reducing each carrier dosage and recruiting T-helper activity by both carriers for each PS.