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

Autor: 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
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Cell Reports, Vol 17, Iss 12, Pp 3193-3205 (2016)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2016.11.060
Popis: 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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