Recognition of Plasmodium falciparum mature gametocyte-infected erythrocytes by antibodies of semi-immune adults and malaria-exposed children from Gabon

Malaria Journal

Research

Michael Theisen¹  Anthony Ajua²  Benjamin Mordmüller³  Meral Esen³  Jana Held³  Peter G. Kremsner³  Tamirat Gebru⁴  Ulysse Ateba Ngoa⁵  Ayola A. Adegnika⁵  Saadou Issifou⁶ 

[1] Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark;Center for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark;Institute of Tropical Medicine, University of Tübingen, Wilhelmstraße 27, 72074, Tübingen, Germany;German Centre for Infection Research (DZIF), Partner Site Tübingen, Germany;Institute of Tropical Medicine, University of Tübingen, Wilhelmstraße 27, 72074, Tübingen, Germany;German Centre for Infection Research (DZIF), Partner Site Tübingen, Germany;Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon;German Centre for Infection Research (DZIF), Partner Site Lambaréné, Gabon;Institute of Tropical Medicine, University of Tübingen, Wilhelmstraße 27, 72074, Tübingen, Germany;German Centre for Infection Research (DZIF), Partner Site Tübingen, Germany;Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon;German Centre for Infection Research (DZIF), Partner Site Lambaréné, Gabon;Department of Medical Laboratory Sciences, College of Medical and Health Sciences, Haramaya University, Harar, Ethiopia;Institute of Tropical Medicine, University of Tübingen, Wilhelmstraße 27, 72074, Tübingen, Germany;German Centre for Infection Research (DZIF), Partner Site Tübingen, Germany;Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon;German Centre for Infection Research (DZIF), Partner Site Lambaréné, Gabon;Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands;Institute of Tropical Medicine, University of Tübingen, Wilhelmstraße 27, 72074, Tübingen, Germany;German Centre for Infection Research (DZIF), Partner Site Tübingen, Germany;Fondation pour la Recherche Scientifique (FORS), Cotonou, Benin;

关键词: Malaria;    Transmission blocking;    Plasmodium falciparum;    Clinical isolates;    Helminths;    Ascaris lumbricoides;    Trichuris trichiura;    GMZ2;    Immune modulation;   

DOI  :  10.1186/s12936-017-1827-7

 received in 2017-02-10, accepted in 2017-04-19,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundTransmission of malaria from man to mosquito depends on the presence of gametocytes, the sexual stage of Plasmodium parasites in the infected host. Naturally acquired antibodies against gametocytes exist and may play a role in controlling transmission by limiting the gametocyte development in the circulation or by interrupting gamete development and fertilization in the mosquito following ingestion. So far, most studies on antibody responses to sexual stage antigens have focused on a subset of gametocyte-surface antigens, even though inhibitory Ab responses to other gametocyte antigens might also play a role in controlling gametocyte density and fertility. Limited information is available on natural antibody response to the surfaces of gametocyte-infected erythrocytes.MethodsAb responses to surface antigens of erythrocytes infected by in vitro differentiated Plasmodium falciparum mature gametocytes were investigated in sera of semi-immune adults and malaria-exposed children. In addition, the effect of immunization with GMZ2, a blood stage malaria vaccine candidate, and the effect of intestinal helminth infection on the development of immunity to gametocytes of P. falciparum was evaluated in malaria-exposed children and adults from Gabon. Serum samples from two Phase I clinical trials conducted in Gabon were analysed by microscopic and flow-cytometric immunofluorescence assay.ResultsAdults had a higher Ab response compared to children. Ab reactivity was significantly higher after fixation and permeabilization of parasitized erythrocytes. Following vaccination with the malaria vaccine candidate GMZ2, anti-gametocyte Ab concentration decreased in adults compared to baseline. Ab response to whole asexual stage antigens had a significant but weak positive correlation to anti-gametocyte Ab responses in adults, but not in children. Children infected with Ascaris lumbricoides had a significantly higher anti-gametocyte Ab response compared to non-infected children.ConclusionThe current data suggest that antigens exposed on the gametocyte-infected red blood cells are recognized by serum antibodies from malaria-exposed children and semi-immune adults. This anti-gametocyte immune response may be influenced by natural exposure and vaccination. Modulation of the natural immune response to gametocytes by co-infecting parasites should be investigated further and may have an important impact on malaria control strategies.

【 授权许可】

CC BY   
© The Author(s) 2017