Antibody signatures in Plasmodium falciparum and helminth infections: immune deviation, serological diagnosis and vaccine responses
[eng] INTRODUCTION: Some of the infectious agents that affect the largest proportion of the world population are Plasmodium falciparum and helminths such as soil-transmitted helminths (STH) and Schistosoma spp. The geographical distribution of these parasites has a great overlap, particularly in sub...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/207925 |
| Acceso en línea: | https://hdl.handle.net/2445/207925 http://hdl.handle.net/10803/690146 |
| Access Level: | acceso abierto |
| Palabra clave: | Immunologia Plasmodium falciparum Immunoglobulines Vacunes Immunology Immunoglobulins Vaccines |
| Sumario: | [eng] INTRODUCTION: Some of the infectious agents that affect the largest proportion of the world population are Plasmodium falciparum and helminths such as soil-transmitted helminths (STH) and Schistosoma spp. The geographical distribution of these parasites has a great overlap, particularly in sub-Saharan Africa. This implies that coinfections with both types of parasites are very frequent. Control and, ultimately, elimination of these infections entails a coordination of efforts directed at several fronts, such as appropriate diagnosis and the development of effective vaccines that prevent these infections in first place. To achieve this, one of the key elements is to understand natural and protective immune responses to infectious diseases and the factors that deviate them. Antibodies play a central role in immunity to infectious diseases and vaccines. They provide valuable insights into historical exposure, current status and prospective susceptibility to infection and disease. Therefore, by studying antibody responses to these infections and to vaccines we can identify beneficial mechanisms to potentiate and negative ones to avoid. In this endeavor, it is crucial to consider the possible interference between organisms with different immunological requirements, such as P. falciparum and helminths, whether it is during current coinfections or as a result of repeated exposure. As an intracellular pathogen, the protective immune responses to P. falciparum are characterized initially by inflammatory cytokines with a type 1 helper T cell (TH1) profile and production of antibodies with cytophilic properties, mainly immunoglobulin (Ig) G1 and IgG3. In contrast, non-cytophilic IgG2 and IgG4 have been mainly associated with risk. In the case of helminths, the prototypical protective immune response is characterized by type 2 helper T cell (TH2) cytokines and the production of IgE antibodies. However, helminths have potent immunomodulatory effects, resulting in a switch to a regulatory helper T cell (TREG) phenotype, as evidenced by the dominance of regulatory cytokines in chronic infections and characterized by the production of IgG4. This regulatory response dampens TH1 and TH2 responses and it is thought to affect not only helminth but also bystander antigens and infections. HYPOTHESES: The primary hypothesis of this doctoral thesis is that immune deviation phenomena alter the quantity and quality of antibody responses, impacting naturally acquired immunity (NAI) to pathogens and the response to vaccines. Immune deviation might be caused by past exposure to and current coinfections with pathogens that induce different types of immune responses, such as P. falciparum and helminths. The secondary hypothesis is that antibody responses to parasite antigens are useful biomarkers for diagnosis and for measuring exposure in the context of infection surveillance, control and elimination strategies for parasites of global health importance. OBJECTIVES: The primary objective of this doctoral thesis is to characterize the phenomenon of immune deviation in terms of antibody responses in the context of past exposure and current coinfection with P. falciparum and helminths, and in the response to the RTS,S/AS01E malaria vaccine. The secondary objective is to evaluate the performance of P. falciparum- and helminth-specific IgG serology and total IgE responses as diagnostic and exposure markers. |
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