The TLR9 ligand CpG promotes the acquisition of Plasmodium falciparum-specific memory B cells in malaria-naive individuals.

Abstract

Despite the central role of memory B cells (MBC) in protective immune responses, little is understood about how they are acquired in naive individuals in response to Ag exposure, and how this process is influenced by concurrent activation of the innate immune system's TLR. In this longitudinal study of malaria-naive individuals, we examined the MBC response to two candidate malaria vaccines administered with or without CpG, a TLR9 ligand. We show that the acquisition of MBC is a dynamic process in which the vaccine-specific MBC pool rapidly expands and then contracts, and that CpG enhances the kinetics, magnitude, and longevity of this response. We observed that the percentage of vaccine-specific MBC present at the time of reimmunization predicts vaccine-specific Ab levels 14 days later; and that at steady-state, there is a positive correlation between vaccine-specific MBC and Ab levels. An examination of the total circulating MBC and plasma cell pools also suggests that MBC differentiate into plasma cells through polyclonal activation, independent of Ag specificity. These results provide important insights into the human MBC response, which can inform the development of vaccines against malaria and other pathogens that disrupt immunological memory.

• Authors: Peter D Crompton, Marko Mircetic, Greta Weiss, Amy Baughman, Chiung-Yu Huang, David J Topham, John J Treanor, Iñaki Sanz, F Eun-Hyung Lee, Anna P Durbin, Kazutoyo Miura, David L Narum, Ruth D Ellis, Elissa Malkin, Gregory E D Mullen, Louis H Miller, Laura B Martin, Susan K Pierce
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 182 Issue 5 Pg. 3318-26 (Mar 01 2009) ISSN: 1550-6606 [Electronic] United States
• PMID: 19234231 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Adjuvants, Immunologic
• CPG-oligonucleotide
• Epitopes, B-Lymphocyte
• Ligands
• Malaria Vaccines
• Oligodeoxyribonucleotides
• ProMune
• TLR9 protein, human
• Toll-Like Receptor 9
• Aluminum Hydroxide

Topics

• Adjuvants, Immunologic (administration & dosage)
• Adult
• Aluminum Hydroxide (administration & dosage, immunology)
• Animals
• B-Lymphocyte Subsets (immunology, metabolism)
• Cells, Cultured
• Clinical Trials, Phase I as Topic
• CpG Islands (immunology)
• Epitopes, B-Lymphocyte (immunology)
• Humans
• Immunization, Secondary
• Immunologic Memory
• Ligands
• Malaria (immunology)
• Malaria Vaccines (administration & dosage, immunology)
• Oligodeoxyribonucleotides (administration & dosage, metabolism)
• Plasmodium falciparum (immunology)
• Toll-Like Receptor 9 (administration & dosage, metabolism)