title: The generation and evaluation of two panels of epitope-matched mouse IgG1, IgG2a, IgG2b and IgG3 antibodies specific for Plasmodium falciparum and Plasmodium yoelii merozoite surface protein 1-19 (MSP1(19)).
abstract: Murine immunoglobulin G (IgG) plays an important role in mediating protective immune responses to malaria. We still know relatively little about which IgG subclasses protect against this disease in mouse models, although IgG2a and IgG2b are considered to be the most potent and dominate in successful passive transfer experiments in rodent malarias. To explore the mechanism(s) by which the different mouse IgG subclasses may mediate a protective effect, we generated mouse IgG1, IgG2a, IgG2b and IgG3 specific for the C-terminal 19-kDa region of Plasmodium falciparum merozoite surface protein 1 (PfMSP1(19)), and to the homologous antigen from Plasmodium yoelii (P. yoelii), both major targets of protective immune responses. This panel of eight IgGs bound antigen with an affinity comparable to that seen for their epitope-matched parental monoclonal antibodies (mAbs) from which they were derived, although for reasons of yield, we were only able to explore the function of mouse IgG1 recognizing PfMSP1(19) in detail, both in vitro and in vivo. Murine IgG1 was as effective as the parental human IgG from which it was derived at inducing NADPH-mediated oxidative bursts and degranulation from neutrophils. Despite showing efficacy in in vitro functional assays with neutrophils, the mouse IgG1 failed to protect against parasite challenge in vivo. The lack of protection afforded by MSP1(19)-specific IgG1 against parasite challenge in wild type mice suggests that this Ab class does not play a major role in the control of infection with mouse malaria in the Plasmodium berghei transgenic model.
authors.affiliation: Lab C4, Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK. sbxjra@nottingham.ac.uk
authors.forename: Jaime R
authors.initials: JR
authors.lastname: Adame-Gallegos
authors.forename: Jianguo
authors.initials: J
authors.lastname: Shi
authors.forename: Richard S
authors.initials: RS
authors.lastname: McIntosh
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Pleass
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000276:immunology; D000918:Antibody Specificity; D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000145:classification / Q000276:immunology; D008288:Malaria / Q000517:prevention & control; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010962:Plasmodium berghei / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D010967:Plasmodium yoelii / Q000276:immunology*; D016415:Sequence Alignment; D013047:Specific Pathogen-Free Organisms
chemical_list: D000913:Antibodies, Protozoan; D000939:Epitopes; D007074:Immunoglobulin G; D020066:Merozoite Surface Protein 1