Vaccine-induced carbohydrate-specific memory B cells reactivate during rodent malaria infection

Joseph, Hayley, Tan, Qiao Ye, Mazhari, Ramin, Eriksson, Emily M., and Schofield, Louis (2019) Vaccine-induced carbohydrate-specific memory B cells reactivate during rodent malaria infection. Frontiers in Immunology, 10. 1840.

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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.

Item ID: 59987
Item Type: Article (Research - C1)
ISSN: 1664-3224
Keywords: malaria, B cell immunity, vaccines, memory failure, glycosylphosphatidylinositol (GPI)
Copyright Information: Copyright © 2019 Joseph, Tan, Mazhari, Eriksson and Schofield. This is an open-access article distributed under the terms of the Creative Commons AttributionLicense (CC BY). The use, distribution or reproduction in other forums is permitted,provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Funders: National Health and Medical Research Council (NHMRC), Bill and Melinda Gates Foundation (BMGF)
Projects and Grants: NHMRC GNT1052580, NHMRC GNT1052580, BMGF OPP1136441
Date Deposited: 21 Aug 2019 07:39
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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