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Published on: April 29, 2015
Immunologic memory response induced by a meningococcal serogroup C conjugate vaccine using the P64k recombinant
María Guirola1, Dioslaida Urquiza, Anabel Alvarez
1Vaccines Division, Centro de Ingenieria Genetica y Biotechnologia, Ciudad de La Habana, Cuba. guirolamaria@yahoo.com
Insights
The P64k protein carrier enhances the meningococcal conjugate vaccine by inducing a robust, long-lasting T-cell dependent immunologic memory response to the polysaccharide antigen.
Area of Science:
- Immunology
- Vaccinology
- Microbial Pathogenesis
Background:
- Meningococcal serogroup C conjugate vaccines are crucial for preventing bacterial meningitis.
- Understanding the mechanisms of immunologic memory induction is vital for vaccine development.
- The role of carrier proteins in modulating immune responses to polysaccharide antigens requires further elucidation.
Purpose of the Study:
- To evaluate the P64k recombinant protein's capacity to recruit T-helper activity.
- To assess the induction of immunologic memory response to the polysaccharide moiety of a meningococcal serogroup C conjugate vaccine.
- To determine if P64k facilitates a switch from T-cell independent to T-cell dependent immune responses.
Main Methods:
- Adoptive lymphocyte transfer experiments in mice.
- Immunization with meningococcal serogroup C glycoconjugate vaccine, plain polysaccharide, or phosphate.
- Analysis of anamnestic immune responses, including antibody titers, isotype switching, and kinetics.
- Infant rat passive protection assay and bactericidal assays.
Main Results:
- Splenocytes from conjugate-vaccinated mice conferred antipolysaccharide immunologic memory to naive recipients.
- The memory response exhibited faster kinetics, IgM to IgG isotype switching, and higher antibody titers compared to controls.
- Sera from conjugate-vaccinated mice demonstrated protective efficacy in infant rats and higher bactericidal titers.
- P64k as a carrier promoted a T-cell dependent memory response to the polysaccharide.
Conclusions:
- The P64k protein acts as an effective carrier, inducing a T-cell dependent immunologic memory response to the polysaccharide antigen.
- This mechanism enhances vaccine efficacy by generating a more robust and protective immune memory.
- The findings support the use of P64k in developing improved conjugate vaccines against meningococcal serogroup C.
Abstract:
In this study, we used an adoptive lymphocyte transfer experiment to evaluate the ability of the P64k recombinant protein to recruit T-helper activity and induce immunologic memory response to the polysaccharide moiety in a meningococcal serogroup C conjugate vaccine. Adoptive transfer of splenocytes from mice immunized with the glycoconjugate conferred antipolysaccharide immunologic memory to naive recipient mice. The observed anamnestic immune response was characterized by more rapid kinetics, isotype switching from IgM to IgG and higher antipolysaccharide antibody titers compared with those reached in groups transferred with splenocytes from plain polysaccharide or phosphate-immunized mice. The memory response generated was also long lasting. Sera from mice transferred with cells from conjugate-immunized mice were the only protective in the infant rat passive protection assay, and also showed higher bactericidal titers. We demonstrated that priming the mice immune system with the glycoconjugate using the P64k protein as carrier induced a memory response to the polysaccharide, promoting a switch of the T-cell-independent response to a T-cell dependent one.
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