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Title: Generation and evaluation of two panels of epitope of murine IgGs targeting Plasmodium falciparum and Plasmodium yoelii merozoite surface protein 1-19 (MSP1-19)
Author: Adame Gallegos, Jaime Raul
ISNI:       0000 0004 2747 1144
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2012
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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 (PfMSPh9), and to the homologous antigen from Plasmodium yoeJii (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 parental monoclonal antibodies (mAbs) from which they were derived. However, during the course of this project for reasons of poor yield, we were only able to explore the function of mouse IgG1 recognizing PfMSP119 in detail, both in vitro and in vivo. Murine IgG1 was as effective as the parental human IgG1 OS1) 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 MSPh9-specific IgG1 against parasite challenge in wild type mice suggests that this Ab class does not play a major role in control of infection with the P. berghei transgenic for PfMSPh9. However, we cannot rule out the possibility that the findings reflect certain shortcomings of the transgenic rodent model of malaria used. Future work aiming to investigate the role of the remaining IgG subclasses targeting PfMSP119, and the complete panel of anti- PyMSP119 Abs, needs to be addressed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available