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

Cell Reports

Stefan H.I. Kappe¹  Nicholas Dambrauskas¹  Ashley M. Vaughan¹  D. Noah Sather¹  Akshay T. Krishnamurty²  William O. Hahn²  Marion Pepper²  Gladys J. Keitany²  Brian D. Hondowicz²  Karen S. Kim² 

[1] Center for Infectious Disease Research, 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA;Department of Immunology, University of Washington School of Medicine, 750 Republican Street, Seattle, WA 98109, USA;

关键词: malaria;    plasmodium;    memory B cells;    attenuated parasites;    vaccines;    antibodies;    humoral immunity;    antigen specific B cells;   

DOI  :  10.1016/j.celrep.2016.11.060

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown