[PDF][PDF] Blood stage malaria disrupts humoral immunity to the pre-erythrocytic stage circumsporozoite protein

GJ Keitany, KS Kim, AT Krishnamurty, BD Hondowicz… - Cell reports, 2016 - cell.com
GJ Keitany, KS Kim, AT Krishnamurty, BD Hondowicz, WO Hahn, N Dambrauskas…
Cell reports, 2016cell.com
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 …
Summary
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.
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