Blood Stage Malaria Disrupts Humoral Immunity to the Pre-erythrocytic Stage Circumsporozoite Protein

Publication date: 20 December 2016
Source:Cell Reports, Volume 17, Issue 12
Author(s): 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
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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Teaser

Individuals in malaria-endemic regions develop poor humoral immunity to pre-erythrocytic Plasmodium antigens. Keitany et al. demonstrate that immunization with genetically attenuated parasites leads to functional memory formation of B cells specific for the pre-erythrocytic antigen, circumsporozoite protein (CSP), yet exposure to blood stage infection suppresses this process.


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