title: 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.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA. pcrompton@niaid.nih.gov
authors.forename: Peter D
authors.initials: PD
authors.lastname: Crompton
authors.forename: Marko
authors.initials: M
authors.lastname: Mircetic
authors.forename: Greta
authors.initials: G
authors.lastname: Weiss
authors.forename: Amy
authors.initials: A
authors.lastname: Baughman
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.forename: David J
authors.initials: DJ
authors.lastname: Topham
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.forename: Iñaki
authors.initials: I
authors.lastname: Sanz
authors.forename: F Eun-Hyung
authors.initials: FE
authors.lastname: Lee
authors.forename: Anna P
authors.initials: AP
authors.lastname: Durbin
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: David L
authors.initials: DL
authors.lastname: Narum
authors.forename: Ruth D
authors.initials: RD
authors.lastname: Ellis
authors.forename: Elissa
authors.initials: E
authors.lastname: Malkin
authors.forename: Gregory E D
authors.initials: GE
authors.lastname: Mullen
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Laura B
authors.initials: LB
authors.lastname: Martin
authors.forename: Susan K
authors.initials: SK
authors.lastname: Pierce
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D017321:Clinical Trials, Phase I as Topic; D018899:CpG Islands / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008024:Ligands; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D018985:Epitopes, B-Lymphocyte; D008024:Ligands; D017780:Malaria Vaccines; D009838:Oligodeoxyribonucleotides; C483020:ProMune; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D000536:Aluminum Hydroxide