The TLR9 ligand CpG promotes the acquisition of Plasmodium falciparum-specific memory B cells in malaria-naive individuals.
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.
Crompton
Peter D
PD
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA. pcrompton@niaid.nih.gov
Mircetic
Marko
M
Weiss
Greta
G
Baughman
Amy
A
Huang
Chiung-Yu
CY
Topham
David J
DJ
Treanor
John J
JJ
Sanz
Iñaki
I
Lee
F Eun-Hyung
FE
Durbin
Anna P
AP
Miura
Kazutoyo
K
Narum
David L
DL
Ellis
Ruth D
RD
Malkin
Elissa
E
Mullen
Gregory E D
GE
Miller
Louis H
LH
Martin
Laura B
LB
Pierce
Susan K
SK
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
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