ORCID Profile
0000-0003-3510-4590
Current Organisation
Universidade Federal de Minas Gerais
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Publisher: Public Library of Science (PLoS)
Date: 27-01-2016
Publisher: Elsevier BV
Date: 23-01-2006
DOI: 10.1016/J.VACCINE.2005.07.091
Abstract: While X-irradiated live parasites are not an acceptable proposition for human vaccination, they offer a ready experimental system to explore mechanisms by which immunity against hookworm infection may be induced in humans. As such, we sought to further elucidate the details of this highly protective immune response induced by the irradiated vaccine in canids, with special emphasis on the cellular aspects of the response. Vaccination with irradiated L3 induced high production of antibodies and strong PBMCs proliferation to crude L3 antigen preparation. Elevated IL-4 production was also observed in vaccinated dogs, especially in relation to IFN-gamma production (IL-4/IFN-gamma ratio). Serum from vaccinated animals inhibited penetration of L3 through canine skin in vitro by 60%. Finally, vaccinated animals had a strong antibody response to ASP-2, a promising vaccine antigen that is an excretory-secretory product of L3. These results add further support the idea that the Th2 immune response is required to generate protective immunity against hookworm larvae and that ES molecules released during this developmental stage are likely targets of this response.
Publisher: Elsevier BV
Date: 09-2005
DOI: 10.1016/J.VACCINE.2005.04.040
Abstract: The ASP-2 protein secreted by infective larvae of the human hookworm, Necator americanus, is under development as a recombinant vaccine. Recombinant Na-ASP-2 was expressed in Pichia pastoris, and the purified protein was characterized. At the 60 L scale, the 21.3 kDa recombinant protein was produced at a yield of 0.4 g/L. When formulated with Alhydrogel and injected into rats to determine immunological potency, three 50 microg doses of the formulated recombinant protein elicited geometric mean antibody titers up to 1:234,881. Rat anti-Na-ASP-2 antibody recognized larval-derived ASP-2 and also inhibited larval migration through skin in vitro. The processes developed and tested for the high yield production of recombinant Na-ASP-2 provide a foundation for clinical vaccine development.
Publisher: American Society for Microbiology
Date: 17-02-2022
DOI: 10.1128/IAI.00595-21
Abstract: Ascariasis is a neglected tropical disease that is widespread in the world and has important socioeconomic impacts. The presence of various stages of worm development in the pulmonary and intestinal mucosae induces a humoral and cellular immune response. However, although there is much evidence of the protective role of mucosal immunity against various pathogens, including helminths, there is still a gap in the knowledge about the immune response and the mechanisms of action that are involved in protection against diseases, especially in the initial phase of ascariasis. Thus, the aim of this study was to evaluate the kinetic aspects of the immune parasitological parameters in intestinal and pulmonary mucosae in male mice with early ascariasis.
Publisher: Public Library of Science (PLoS)
Date: 16-11-2021
DOI: 10.1371/JOURNAL.PPAT.1010067
Abstract: Human ascariasis is the most prevalent but neglected tropical disease in the world, affecting approximately 450 million people. The initial phase of Ascaris infection is marked by larval migration from the host’s organs, causing mechanical injuries followed by an intense local inflammatory response, which is characterized mainly by neutrophil and eosinophil infiltration, especially in the lungs. During the pulmonary phase, the lesions induced by larval migration and excessive immune responses contribute to tissue remodeling marked by fibrosis and lung dysfunction. In this study, we investigated the relationship between SIgA levels and eosinophils. We found that TLR2 and TLR4 signaling induces eosinophils and promotes SIgA production during Ascaris suum infection. Therefore, control of parasite burden during the pulmonary phase of ascariasis involves eosinophil influx and subsequent promotion of SIgA levels. In addition, we also demonstrate that eosinophils also participate in the process of tissue remodeling after lung injury caused by larval migration, contributing to pulmonary fibrosis and dysfunction in re-infected mice. In conclusion, we postulate that eosinophils play a central role in mediating host innate and humoral immune responses by controlling parasite burden, tissue inflammation, and remodeling during Ascaris suum infection. Furthermore, we suggest that the use of probiotics can induce eosinophilia and SIgA production and contribute to controlling parasite burden and morbidity of helminthic diseases with pulmonary cycles.
Publisher: American Society for Microbiology
Date: 03-2007
DOI: 10.1128/CVI.00404-06
Abstract: Hookworm infection is one of most important parasitic infection of humans, occurring in 740 million people. Here we report the protective vaccination of dogs with Ac -16, an immunodominant surface antigen from the hookworm Ancylostoma caninum . We show that immunization with Ac -16 formulated with AS03 elicited specific humoral and cellular immune responses and provided partial protection against hookworm infection and morbidity as evidenced by a significant reduction of hookworm egg counts (64% reduction P = 0.0078) and worm-induced blood loss ( P 0.05). Moreover, specific anti- Ac -16 antibodies recognized the native protein on the surface of third-stage larvae and blocked their migration through tissue in vitro. Our data support the use of Ac -16 as a potential candidate for vaccination against hookworm infection.
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.EXPPARA.2022.108267
Abstract: Human ascariasis is one of the most prevalent neglected tropical diseases worldwide. The immune response during human ascariasis is characterized by Th2 polarization and a mixed Th2/Th17 response during the pathogenesis of experimental larval ascariasis. Cytokines and other pro-inflammatory mediators, such as nitric oxide (NO), are involved in helminthic infections. However, the role of NO in ascariasis remains unclear. Given the importance of NO in inflammation, we aimed to determine the immunological and histopathological alterations in the livers of C57BL/6 iNOS In this study, parasitic load was evaluated in the livers of wild type C57BL/6 and C57BL/6 iNOS The results showed that NO is important for controlling parasitic load during infection by A. suum. C57BL/6iNOS We demonstrated that NO is a crucial inflammatory molecule during Ascaris sp. infection and controls the establishment of the parasite and the development of the host immune response in the liver.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.IJPARA.2013.02.009
Abstract: Studies related to the immunobiological aspects of an Ascaris spp. infection are still scarce, especially those that aim to elucidate the early events of the immune response. In this study, we demonstrated a novel standardized method for early experimental Ascaris infection, providing additional information about the infectivity of eggs embryonated in vitro as well as the influence of host age on development of the infection. Finally, we characterised the immunopathology of early infection, focusing on the tissue and systemic cytokine profiles and the histopathology of infection in the lungs of BALB/c mice. Our results demonstrated that the highest egg infectivity occurred on the 100th and 200th days of in vitro embryonation and that 8 week-old BALB/c mice were more susceptible to infection than 16 week-old mice. Ascaris-infected mice showed an early, significant level of IL-5 production in the lungs 4 days p.i., followed by an increase in the level of neutrophils in the inflammatory infiltrate at 8 days p.i, which was correlated with the peak of larval migration in the tissue and a significant level of IL-6 production. The inflammatory infiltrate in the lungs was gradually replaced by mononuclear cells and eosinophils on the 10th and 12th days p.i., respectively, and an increase in TNF levels was observed. The downmodulation of systemic TCD4(+) cell numbers might suggest that T cell hyporesponsiveness was induced by the Ascaris spp. larvae, contributing to safeguarding parasite survival during larval migration. Taken together, the novel aspects of Ascaris infection presented here enabled a better understanding of the immunopathological events during larval migration, providing insight for further studies focused on immunisation and immunoprophylatic assays.
Publisher: American Society for Microbiology
Date: 10-2005
DOI: 10.1128/IAI.73.10.6903-6911.2005
Abstract: We report the cloning and expression of Ac -GST-1, a novel glutathione S -transferase from the adult hookworm Ancylostoma caninum , and its possible role in parasite blood feeding and as a vaccine target. The predicted Ac -GST-1 open reading frame contains 207 amino acids (mass, 24 kDa) and exhibited up to 65% amino acid identity with other nematode GSTs. mRNA encoding Ac -GST-1 was detected in adults, eggs, and larval stages, but the protein was detected only in adult hookworm somatic extracts and excretory/secretory products. Using antiserum to the recombinant protein, Ac -GST-1 was immunolocalized to the parasite hypodermis and muscle tissue and weakly to the intestine. Recombinant Ac -GST-1 was enzymatically active, as determined by conjugation of glutathione to a model substrate, and exhibited a novel high-affinity binding site for hematin. The possible role of Ac -GST-1 in parasite heme detoxification during hemoglobin digestion or heme uptake prompted interest in evaluating it as a potential vaccine antigen. Vaccination of dogs with Ac -GST-1 resulted in a 39.4% reduction in the mean worm burden and 32.3% reduction in egg counts compared to control dogs following larval challenge, although the reductions were not statistically significant. However, hamsters vaccinated with Ac -GST-1 exhibited statistically significant worm reduction (53.7%) following challenge with heterologous Necator americanus larvae. These studies suggest that Ac -GST-1 is a possible drug and vaccine target for hookworm infection.
Publisher: Cold Spring Harbor Laboratory
Date: 03-09-2018
DOI: 10.1101/406843
Abstract: The human hookworm Necator americanus infects more than 400 million people worldwide, contributing substantially to the poverty in these regions. Adult stage N. americanus live in the small intestine of the human host where they inject excretory/secretory (ES) products into the mucosa. ES products have been characterized at the proteome level for a number of animal hookworm species, but until now, the difficulty in obtaining sufficient live N. americanus has been an obstacle in characterizing the secretome of this important human pathogen. Herein we describe the ES proteome of N. americanus and utilize this information to conduct the first proteogenomic analysis of a parasitic helminth, significantly improving the available genome and thereby generating a robust description of the parasite secretome. The genome annotation resulted in a a revised prediction of 3,425 fewer genes than initially reported, accompanied by a significant increase in the number of exons and introns, total gene length and the percentage of the genome covered by genes. Almost 200 ES proteins were identified by LC-MS/MS with SCP/TAPS proteins, ‘hypothetical’ proteins and proteases among the most abundant families. These proteins were compared to commonly used model species of human parasitic infections, including Ancylostoma caninum, Nippostrongylus brasiliensis and Heligmosomoides polygyrus . Our findings provide valuable information on important families of proteins with both known and unknown functions that could be instrumental in host-parasite interactions, including protein families that might be key for parasite survival in the onslaught of robust immune responses, as well as vaccine and drug targets.
Publisher: Public Library of Science (PLoS)
Date: 26-05-2020
Publisher: Research Trends, Ltd.
Date: 17-06-2021
No related grants have been discovered for Lilian Bueno.