Circumsporozoite Surface Protein-based malaria vaccines: a review

Malaria represents a serious public health problem, presenting with high rates of incidence, morbidity and mortality in tropical and subtropical regions of the world. According to the World Health Organization, in 2018 there were 228 million cases and 405 thousand deaths caused by this disease in the world, affecting mainly children and pregnant women in Africa. Despite the programs carried out to control this disease, drug resistance and invertebrate vector resistance to insecticides have generated difficulties. An efficient vaccine against malaria would be a strategy with a high impact on the eradication and control of this disease. Researches aimed at developing vaccines have focused on antigens of high importance for the survival of the parasite such as the Circumsporozoite Surface Protein, involved in the pre-erythrocytic cycle during parasites invasion in hepatocytes. Currently, RTS’S is the most promising vaccine for malaria and was constructed using CSP; its performance was evaluated using two types of adjuvants: AS01 and AS02. The purpose of this review was to provide a bibliographic survey of historical researches that led to the development of RTS’S and its performance analysis over the decade. The search for new adjuvants to be associated with this antigen seems to be a way to obtain higher percentages of protection for a future malaria vaccine

Sofosbuvir and daclatasvir combination therapy for current hepatitis C virus genotype 4 achieves SVR: a case report of HCV genotype 4 from the Amazon

Abstract Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region

Sofosbuvir and daclatasvir combination therapy for current hepatitis C virus genotype 4 achieves SVR: a case report of HCV genotype 4 from the Amazon

<div><p>Abstract Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region.</p></div

Combined impact of hepatitis C virus genotype 1 and interleukin-6 and tumor necrosis factor-α polymorphisms on serum levels of pro-inflammatory cytokines in Brazilian HCV-infected patients

We investigated the association between hepatitis C virus (HCV) genotypes and host cytokine gene polymorphisms and serum cytokine levels in patients with chronic hepatitis C. Serum IL-6, TNF-α, IL-2, IFN-γ, IL-4, IL-10, and IL-17A levels were measured in 67 HCV patients (68.2% genotype 1 [G1]) and 47 healthy controls. The HCV patients had higher IL-6, IL-2, IFN-γ, IL-10, and IL-17A levels than the controls. HCV G1 patients had higher IL-2 and IFN-γ levels than G2 patients. The -174IL6G>. C, -308TNFαG>. A, and -1082IL10A>. G variants were similarly distributed in both groups. However, HCV patients with the -174IL6GC variant had higher IL-2 and IFN-γ levels than patients with the GG and CC variants. Additionally, HCV patients with the -308TNFαGG genotype had higher IL-17A levels than patients with the AG genotype, whereas patients with the -1082IL10GG variant had higher IL-6 levels than patients with the AA and AG variants. A significant proportion of HCV patients had high levels of both IL-2 and IFN-γ. The subgroup of HCV patients with the G1/IL6CG/TNFαGG association displayed the highest proportions of high producers of IL-2 and IFN-γ whereas the subgroup with the G1/TNFαGG profile showed high proportions of high producers of IL-6 and IL-17A. HCV patients with other HCV/cytokine genotype associations showed no particular cytokine profile. Our results suggest that HCV genotype G1 and IL-6 and TNF-α polymorphisms have a clinically relevant influence on serum pro-inflammatory cytokine profile (IL-2 and IFN-γ) in HCV patients. © 2014 American Society for Histocompatibility and Immunogenetics

Translating Unconventional T Cells and Their Roles in Leukemia Antitumor Immunity

Recently, cell-mediated immune response in malignant neoplasms has become the focus in immunotherapy against cancer. However, in leukemia, most studies on the cytotoxic potential of T cells have concentrated only on T cells that recognize peptide antigens (Ag) presented by polymorphic molecules of the major histocompatibility complex (MHC). This ignores the great potential of unconventional T cell populations, which include gamma-delta T cells (γδ), natural killer T cells (NKT), and mucosal-associated invariant T cells (MAIT). Collectively, these T cell populations can recognize lipid antigens, specially modified peptides and small molecule metabolites, in addition to having several other advantages, which can provide more effective applications in cancer immunotherapy. In recent years, these cell populations have been associated with a repertoire of anti- or protumor responses and play important roles in the dynamics of solid tumors and hematological malignancies, thus, encouraging the development of new investigations in the area. This review focuses on the current knowledge regarding the role of unconventional T cell populations in the antitumor immune response in leukemia and discusses why further studies on the immunotherapeutic potential of these cells are needed

The Robust and Modulated Biomarker Network Elicited by the Plasmodium vivax Infection Is Mainly Mediated by the IL-6/IL-10 Axis and Is Associated with the Parasite Load

Submitted by Nuzia Santos ([email protected]) on 2015-02-09T16:36:53Z No. of bitstreams: 1 2014_056.pdf: 2001433 bytes, checksum: f5ee8a7b58b1f7532b4e1e0b3ea10bec (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-02-09T16:38:53Z (GMT) No. of bitstreams: 1 2014_056.pdf: 2001433 bytes, checksum: f5ee8a7b58b1f7532b4e1e0b3ea10bec (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-02-09T16:50:34Z (GMT) No. of bitstreams: 1 2014_056.pdf: 2001433 bytes, checksum: f5ee8a7b58b1f7532b4e1e0b3ea10bec (MD5)Made available in DSpace on 2015-02-09T16:50:34Z (GMT). No. of bitstreams: 1 2014_056.pdf: 2001433 bytes, checksum: f5ee8a7b58b1f7532b4e1e0b3ea10bec (MD5) Previous issue date: 2014Universidade Federal do Amazonas. Programa de Pós-Graduação em Imunologia Básica e Aplicada. Manaus, AM, Brazil/ Fundação de Hematologia e Hemoterapia do Amazonas. Departamento de Ensino e Pesquisa. Manaus, AM, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, BrazilUniversidade Federal do Amazonas. Programa de Pós-Graduação em Imunologia Básica e Aplicada. Manaus, AM, Brazil/ Fundação Oswaldo Cruz. Centro de Pesquisas Leônidas e Maria Deane. Manaus, AM, BrazilFundação de Hematologia e Hemoterapia do Amazonas. Departamento de Ensino e Pesquisa. Manaus, AM, BrazilUniversidade Federal do Amazonas. Programa de Pós-Graduação em Imunologia Básica e Aplicada. Manaus, AM, Brazil/ Fundação de Hematologia e Hemoterapia do Amazonas. Departamento de Ensino e Pesquisa. Manaus, AM, BrazilFundação de Medicina Tropical Doutor Heitor Vieira Dourado. Instituto de Medicina Tropical de Coari. Coari, AM, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Leônidas e Maria Deane. Manaus, AM, BrazilUniversidade Federal do Amazonas. Programa de Pós-Graduação em Imunologia Básica e Aplicada. Manaus, AM, BrazilUniversidade Federal do Amazonas. Programa de Pós-Graduação em Imunologia Básica e Aplicada. Manaus, AM, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, BrazilUniversidade Federal do Amazonas. Programa de Pós-Graduação em Imunologia Básica e Aplicada. Manaus, AM, Brazil/ Fundação de Hematologia e Hemoterapia do Amazonas. Departamento de Ensino e Pesquisa. Manaus, AM, BrazilBackground. Recent studies have shown that the inflammatory process, including the biomarker production, and the intense activation of innate immune responses are greater in the malaria caused by Plasmodium vivax than other species. Here, we examined the levels of serum biomarkers and their interaction during acute malaria. Material and Methods. Blood samples were collected from P. vivax-infected patients at admission and from healthy donors. Levels of serum biomarkers were measured by Cytometric Bead Assay or ELISA. Results.P. vivax infection triggered the production of both inflammatory and regulatory biomarkers. Levels of IL-6, CXCL-8, IFN-γ, IL-5, and IL-10 were higher in P. vivax-infected patients than in healthy donors. On the other hand, malaria patients produced lower levels of TNF-α, IL-12p70, and IL-2 than healthy individuals. While the levels of IL-10 and IL-6 were found independent on the number of malaria episodes, higher levels of these cytokines were seen in patients with higher parasite load. Conclusion. A mixed pattern of proinflammatory and regulatory biomarkers is produced in P. vivax malaria. Analysis of biomarker network suggests that IL-10 and IL-6 are a robust axis in malaria patients and that this interaction seems to be associated with the parasite load