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Front Immunol. 2019 Aug 9;10:1840. doi: 10.3389/fimmu.2019.01840. eCollection 2019.

Vaccine-Induced Carbohydrate-Specific Memory B Cells Reactivate During Rodent Malaria Infection.

Author information

1
Division of Population Health and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
2
Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia.
3
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, Australia.

Abstract

A long-standing challenge in malaria is the limited understanding of B cell immunity, previously hampered by lack of tools to phenotype rare antigen-specific cells. Our aim was to develop a method for identifying carbohydrate-specific B cells within lymphocyte populations and to determine whether a candidate vaccine generated functional memory B cells (MBCs) that reactivated upon challenge with Plasmodium (pRBCs). To this end, a new flow cytometric probe was validated and used to determine the kinetics of B cell activation against the candidate vaccine glycosylphosphatidylinositol conjugated to Keyhole Limpet Haemocyanin (GPI-KLH). Additionally, immunized C57BL/6 mice were rested (10 weeks) and challenged with pRBCs or GPI-KLH to assess memory B cell recall against foreign antigen. We found that GPI-specific B cells were detectable in GPI-KLH vaccinated mice, but not in Plasmodium-infected mice. Additionally, in previously vaccinated mice GPI-specific IgG1 MBCs were reactivated against both pRBCs and synthetic GPI-KLH, which resulted in increased serum levels of anti-GPI IgG in both challenge approaches. Collectively our findings contribute to the understanding of B cell immunity in malaria and have important clinical implications for inclusion of carbohydrate conjugates in malaria vaccines.

KEYWORDS:

B cell immunity; glycosylphosphatidylinositol (GPI); malaria; memory failure; vaccines

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