Blood Stage Malaria Disrupts Humoral Immunity to the Pre-erythrocytic Stage Circumsporozoite Protein
Gladys J Keitany, Karen S Kim, Akshay T Krishnamurty, Brian D Hondowicz, William O Hahn, Nicholas Dambrauskas, D Noah Sather, Ashley M Vaughan, Stefan H I Kappe, Marion Pepper, Gladys J Keitany, Karen S Kim, Akshay T Krishnamurty, Brian D Hondowicz, William O Hahn, Nicholas Dambrauskas, D Noah Sather, Ashley M Vaughan, Stefan H I Kappe, Marion Pepper
Abstract
Many current malaria vaccines target the pre-erythrocytic stage of infection in the liver. However, in malaria-endemic regions, increased blood stage exposure is associated with decreased vaccine efficacy, thereby challenging current vaccine efforts. We hypothesized that pre-erythrocytic humoral immunity is directly disrupted by blood stage infection. To investigate this possibility, we used Plasmodium-antigen tetramers to analyze B cells after infection with either late liver stage arresting parasites or wild-type parasites that progress to the blood stage. Our data demonstrate that immunoglobulin G (IgG) antibodies against the pre-erythrocytic antigen, circumsporozoite protein (CSP), are generated only in response to the attenuated, but not the wild-type, infection. Further analyses revealed that blood stage malaria inhibits CSP-specific germinal center B cell differentiation and modulates chemokine expression. This results in aberrant memory formation and the loss of a rapid secondary B cell response. These data highlight how immunization with attenuated parasites may drive optimal immunity to malaria.
Keywords: antibodies; antigen specific B cells; attenuated parasites; humoral immunity; malaria; memory B cells; plasmodium; vaccines.
Conflict of interest statement
All authors in these manuscript have no conflict of interest.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
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Source: PubMed