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  1. Article ; Online: Mucosal and systemic immune correlates of viral control after SARS-CoV-2 infection challenge in seronegative adults.

    Wagstaffe, Helen R / Thwaites, Ryan S / Reynaldi, Arnold / Sidhu, Jasmin K / McKendry, Richard / Ascough, Stephanie / Papargyris, Loukas / Collins, Ashley M / Xu, Jiayun / Lemm, Nana-Marie / Siggins, Matthew K / Chain, Benny M / Killingley, Ben / Kalinova, Mariya / Mann, Alex / Catchpole, Andrew / Davenport, Miles P / Openshaw, Peter J M / Chiu, Christopher

    Science immunology

    2024  Volume 9, Issue 92, Page(s) eadj9285

    Abstract: Human infection challenge permits in-depth, early, and pre-symptomatic characterization of the immune response, enabling the identification of factors that are important for viral clearance. Here, we performed intranasal inoculation of 34 young adult, ... ...

    Abstract Human infection challenge permits in-depth, early, and pre-symptomatic characterization of the immune response, enabling the identification of factors that are important for viral clearance. Here, we performed intranasal inoculation of 34 young adult, seronegative volunteers with a pre-Alpha severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Of these participants, 18 (53%) became infected and showed an interferon-dominated mediator response with divergent kinetics between nasal and systemic sites. Peripheral CD4
    MeSH term(s) Humans ; COVID-19 ; SARS-CoV-2 ; Vaccination ; CD8-Positive T-Lymphocytes ; Nasal Mucosa
    Language English
    Publishing date 2024-02-09
    Publishing country United States
    Document type Journal Article
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.adj9285
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Differential requirement for cathepsin D for processing of the full length and C-terminal fragment of the malaria antigen MSP1.

    Tulone, Calogero / Sponaas, Anne-Marit / Raiber, Eun-Ang / Tabor, Alethea B / Langhorne, Jean / Chain, Benny M

    PloS one

    2011  Volume 6, Issue 10, Page(s) e24886

    Abstract: Merozoite Surface Protein 1 is expressed on the surface of malaria merozoites and is important for invasion of the malaria parasite into erythrocytes. MSP1-specific CD4 T cell responses and antibody can confer protective immunity in experimental models ... ...

    Abstract Merozoite Surface Protein 1 is expressed on the surface of malaria merozoites and is important for invasion of the malaria parasite into erythrocytes. MSP1-specific CD4 T cell responses and antibody can confer protective immunity in experimental models of malaria. In this study we explore the contributions of cathepsins D and E, two aspartic proteinases previously implicated in antigen processing, to generating MSP1 CD4 T-cell epitopes for presentation. The absence of cathepsin D, a late endosome/lysosomal enzyme, is associated with a reduced presentation of MSP1 both following in vitro processing of the epitope MSP1 from infected erythrocytes by bone marrow-derived dendritic cells, and following in vivo processing by splenic CD11c+ dendritic cells. By contrast, processing and presentation of the soluble recombinant protein fragment of MSP1 is unaffected by the absence of cathepsin D, but is inhibited when both cathepsin D and E are absent. The role of different proteinases in generating the CD4 T cell repertoire, therefore, depends on the context in which an antigen is introduced to the immune system.
    MeSH term(s) Animals ; Antibody Formation/drug effects ; Antibody Formation/immunology ; Antigen Presentation/drug effects ; Antigen Presentation/immunology ; Antigens, Protozoan/chemistry ; Antigens, Protozoan/immunology ; Bone Marrow Cells/cytology ; Bone Marrow Cells/drug effects ; Bone Marrow Cells/immunology ; Cathepsin D/deficiency ; Cathepsin D/metabolism ; Chimera/immunology ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Erythrocytes/drug effects ; Erythrocytes/parasitology ; Histocompatibility Antigens Class II/immunology ; Immunoglobulin G/immunology ; Malaria/immunology ; Malaria/parasitology ; Merozoite Surface Protein 1/chemistry ; Merozoite Surface Protein 1/immunology ; Merozoites/drug effects ; Merozoites/immunology ; Mice ; Parasitemia/immunology ; Parasitemia/parasitology ; Phenotype ; Plasmodium chabaudi/drug effects ; Plasmodium chabaudi/immunology ; Protease Inhibitors/pharmacology ; Spleen/drug effects ; Spleen/immunology ; Spleen/parasitology
    Chemical Substances Antigens, Protozoan ; Histocompatibility Antigens Class II ; Immunoglobulin G ; Merozoite Surface Protein 1 ; Protease Inhibitors ; Cathepsin D (EC 3.4.23.5)
    Language English
    Publishing date 2011-10-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0024886
    Database MEDical Literature Analysis and Retrieval System OnLINE

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