Polyclonal B-cell activation in human malaria: relevance to the development of anti-sporozoite specific immune response and of immunopathology in individuals from endemic areas (Rondonia State - Brazil)

Submitted by Sandra Infurna ([email protected]) on 2019-11-06T13:58:05Z No. of bitstreams: 1 ClaudioTD_Ribeiro_etal_IOC_1988.pdf: 290888 bytes, checksum: 7adcc5b866ba2f6d06cc2cc9d40bb169 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-11-06T14:16:46Z (GMT) No. of bitstreams: 1 ClaudioTD_Ribeiro_etal_IOC_1988.pdf: 290888 bytes, checksum: 7adcc5b866ba2f6d06cc2cc9d40bb169 (MD5)Made available in DSpace on 2019-11-06T14:16:46Z (GMT). No. of bitstreams: 1 ClaudioTD_Ribeiro_etal_IOC_1988.pdf: 290888 bytes, checksum: 7adcc5b866ba2f6d06cc2cc9d40bb169 (MD5) Previous issue date: 1988Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Centro Colaborador da OMS para Pesquisa e Treinamento em Imunologia de Doenças Parasitárias. Rio de Janeiro, RJ, Brasil

Recombinant Plasmodium vivax circumsporozoite surface protein allelic variants: antibody recognition by individuals from three communities in the Brazilian Amazon

Circumsporozoite protein (CSP) variants of P. vivax, besides having variations in the protein repetitive portion, can differ from each other in aspects such as geographical distribution, intensity of transmission, vectorial competence and immune response. Such aspects must be considered to P. vivax vaccine development. Therefore, we evaluated the immunogenicity of novel recombinant proteins corresponding to each of the three P. vivax allelic variants (VK210, VK247 and P. vivax-like) and of the C-terminal region (shared by all PvCSP variants) in naturally malaria-exposed populations of Brazilian Amazon. Our results demonstrated that PvCSP-VK210 was the major target of humoral immune response in studied population, presenting higher frequency and magnitude of IgG response. The IgG subclass profile showed a prevalence of cytophilic antibodies (IgG1 and IgG3), that seem to have an essential role in protective immune response. Differently of PvCSP allelic variants, antibodies elicited against C-terminal region of protein did not correlate with epidemiological parameters, bringing additional evidence that humoral response against this protein region is not essential to protective immunity. Taken together, these findings increase the knowledge on serological response to distinct PvCSP allelic variants and may contribute to the development of a global and effective P. vivax vaccine

Evaluation of the genetic polymorphism of Plasmodium falciparum P126 protein (SERA or SERP) and its influence on naturally acquired specific antibody responses in malaria-infected individuals living in the Brazilian Amazon

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>P126 protein is an asexual blood-stage malaria vaccine candidate antigen. Antibodies against P126 are able to inhibit parasite growth <it>in vitro</it>, and a major parasite-inhibitory epitope has been recently mapped to its 47 kDa N-terminal extremity (octamer repeat domain – OR domain). The OR domain basically consists of six octamer units, but variation in the sequence and number of repeat units may appear in different alleles. The aim of the present study was to investigate the polymorphism of P126 N-terminal region OR domain in <it>P. falciparum </it>isolates from two Brazilian malaria endemic areas and its impact on anti-OR naturally acquired antibodies.</p> <p>Methods</p> <p>The study was carried out in two villages, Candeias do Jamari (Rondonia state) and Peixoto de Azevedo (Mato Grosso state), both located in the south-western part of the Amazon region. The repetitive region of the gene encoding the P126 antigen was PCR amplified and sequenced with the di-deoxy chain termination procedure. The antibody response was evaluated by ELISA with the Nt47 synthetic peptide corresponding to the P126 OR-II domain.</p> <p>Results</p> <p>Only two types of OR fragments were identified in the studied areas, one of 175 bp (OR-I) and other of 199 bp (OR-II). A predominance of the OR-II fragment was observed in Candeias do Jamari whereas in Peixoto de Azevedo both fragments OR-I and OR-II were frequent as well as mixed infection (both fragments simultaneously) reported here for the first time. Comparing the DNA sequencing of OR-I and OR-II fragments, there was a high conservation among predicted amino acid sequences of the P126 N-terminal extremity. Data of immune response demonstrated that the OR domain is highly immunogenic in natural conditions of exposure and that the polymorphism of the OR domain does not apparently influence the specific immune response.</p> <p>Conclusion</p> <p>These findings confirm a limited genetic polymorphism of the P126 OR domain in <it>P. falciparum </it>isolates and that this limited genetic polymorphism does not seem to influence the development of a specific humoral immune response to P126 and its immunogenicity in the studied population.</p

The influence of intestinal parasites on Plasmodium vivax-specific antibody responses to MSP-119 and AMA-1 in rural populations of the Brazilian Amazon

Abstract\ud \ud Background\ud Polyparasitism is a common condition in humans but its impact on the host immune system and clinical diseases is still poorly understood. There are few studies of the prevalence and the effect of malaria-intestinal parasite co-infections in the immune response to malaria vaccine candidates. The present study determines whether the presence of malaria and intestinal parasites co-infection is associated with impaired IgG responses to Plasmodium vivax AMA-1 and MSP-119 in a rural population of the Brazilian Amazon.\ud \ud \ud Methods\ud A cross-sectional survey was performed in a rural area of Rondonia State and 279 individuals were included in the present study. At recruitment, whole blood was collected and Plasmodium and intestinal parasites were detected by microscopy and molecular tests. Blood cell count and haemoglobin were also tested and antibody response specific to P. vivax AMA-1 and MSP-119 was measured in plasma by ELISA. The participants were grouped according to their infection status: singly infected with Plasmodium (M); co-infected with Plasmodium and intestinal parasites (CI); singly infected with intestinal parasites (IP) and negative (N) for both malaria and intestinal parasites.\ud \ud \ud Results\ud The prevalence of intestinal parasites was significantly higher in individuals with malaria and protozoan infections were more prevalent. IgG antibodies to PvAMA-1 and/or PvMSP-119 were detected in 74 % of the population. The prevalence of specific IgG was similar for both proteins in all four groups and among the groups the lowest prevalence was in IP group. The cytophilic sub-classes IgG1 and IgG3 were predominant in all groups for PvAMA-1 and IgG1, IgG3 and IgG4 for PvMSP-119. In the case of non-cytophilic antibodies to PvAMA-1, IgG2 was significantly higher in IP and N group when compared to M and CI while IgG4 was higher in IP group.\ud \ud \ud Conclusions\ud The presence of intestinal parasites, mainly protozoans, in malaria co-infected individuals does not seem to alter the antibody immune responses to P. vivax AMA-1 and MSP-119. However, IgG response to both AMA1 and MSP1 were lower in individuals with intestinal parasites.The authors are in debt to the individuals who participated in this study, the\ud Secretary of Health and Laboratory Central (LACEN) of Rondonia, the local\ud malaria control team in Joana D´Arc settlement for their logistic support\ud and the Institute Oswaldo Cruz (Fiocruz) for overall support. This work was\ud supported by PRONEX Malaria network funded by the Brazilian Ministry of\ud Science and Technology (MCT), Conselho Nacional de Desenvolvimento\ud Cientifico e Tecnologico (CNPq, Brazil) and Fundação de Amparo à Pesquisa\ud do Estado do Rio de Janeiro (FAPERJ, Brazil). PROEP, Instituto Oswaldo Cruz\ud (FIOCRUZ, Brazil). JOF is recipient of a Research Productivity Fellowship from\ud CNPq, JCSA is recipient of a fellowship from Instituto Oswaldo Cruz and VAR,\ud MM from CNPq

Influence of HLA-DRB1 and HLA-DQB1 Alleles on IgG Antibody Response to the P. vivax MSP-1, MSP-3α and MSP-9 in Individuals from Brazilian Endemic Area

Background: the antibody response generated during malaria infections is of particular interest, since the production of specific IgG antibodies is required for acquisition of clinical immunity. However, variations in antibody responses could result from genetic polymorphism of the HLA class II genes. Given the increasing focus on the development of subunit vaccines, studies of the influence of class II alleles on the immune response in ethnically diverse populations is important, prior to the implementation of vaccine trials.Methods and Findings: in this study, we evaluated the influence of HLA-DRB1* and -DQB1* allelic groups on the naturally acquired humoral response from Brazilian Amazon individuals (n = 276) against P. vivax Merozoite Surface Protein-1 (MSP-1), MSP-3 alpha and MSP-9 recombinant proteins. Our results provide information concerning these three P. vivax antigens, relevant for their role as immunogenic surface proteins and vaccine candidates. Firstly, the studied population was heterogeneous presenting 13 HLA-DRB1* and 5 DQB1* allelic groups with a higher frequency of HLA-DRB1*04 and HLA-DQB1*03. the proteins studied were broadly immunogenic in a naturally exposed population with high frequency of IgG antibodies against PvMSP1-19 (86.7%), PvMSP-3 (77%) and PvMSP-9 (76%). Moreover, HLA-DRB1*04 and HLA-DQB1*03 alleles were associated with a higher frequency of IgG immune responses against five out of nine antigens tested, while HLA-DRB1* 01 was associated with a high frequency of non-responders to repetitive regions of PvMSP-9, and the DRB1*16 allelic group with the low frequency of responders to PvMSP3 full length recombinant protein.Conclusions: HLA-DRB1*04 alleles were associated with high frequency of antibody responses to five out of nine recombinant proteins tested in Rondonia State, Brazil. These features could increase the success rate of future clinical trials based on these vaccine candidates.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Yerkes National Primate Research Center BaseNational Center for Research Resources of the National Institutes of HealthNIHCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Inst Oswaldo Cruz, Lab Immunoparasitol, BR-20001 Rio de Janeiro, BrazilOswaldo Cruz Fdn Fiocruz, Ctr Technol Dev Hlth CDTS, Rio de Janeiro, BrazilInst Oswaldo Cruz, Lab Simulideos & Oncocercose, BR-20001 Rio de Janeiro, BrazilEmory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USAUniv Estado Rio de Janeiro, Histocompatibil & Cryopreservat Lab, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Escola Paulista Med, São Paulo, BrazilEmory Univ, Sch Med, Div Infect Dis, Atlanta, GA USACDC Natl Ctr Infect Dis, Div Parasit Dis, Atlanta, GA USAUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Escola Paulista Med, São Paulo, BrazilFAPESP: 2009/15132-4Yerkes National Primate Research Center Base: RR00165NIH: RO1 AI0555994Web of Scienc

Evaluation of allelic forms of the erythrocyte binding antigen 175 (EBA-175) in Plasmodium falciparum field isolates from Brazilian endemic area

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>Erythrocyte Binding Antigen-175 (EBA-175) is an antigen considered to be one of the leading malaria vaccine candidates. EBA-175 mediates sialic acid-dependent binding to glycophorin A on the erythrocytes playing a crucial role during invasion of the <it>P. falciparum </it>in the host cell. Dimorphic allele segments, termed C-fragment and F-fragment, have been found in high endemicity malaria areas and associations between the dimorphism and severe malaria have been described. In this study, the genetic dimorphism of EBA-175 was evaluated in <it>P. falciparum </it>field isolates from Brazilian malaria endemic area.</p> <p>Methods</p> <p>The study was carried out in rural villages situated near Porto Velho, Rondonia State in the Brazilian Amazon in three time points between 1993 and 2008. The allelic dimorphism of the EBA-175 was analysed by Nested PCR.</p> <p>Results</p> <p>The classical allelic dimorphism of the EBA-175 was identified in the studied area. Overall, C-fragment was amplified in a higher frequency than F-fragment. The same was observed in the three time points where C-fragment was observed in a higher frequency than F-fragment. Single infections (one fragment amplified) were more frequent than mixed infection (two fragments amplified).</p> <p>Conclusions</p> <p>These findings confirm the dimorphism of EBA175, since only the two types of fragments were amplified, C-fragment and F-fragment. Also, the results show the remarkable predominance of CAMP allele in the studied area. The comparative analysis in three time points indicates that the allelic dimorphism of the EBA-175 is stable over time.</p

Indução de células T CD8+ protetora contra estágios pré-eritrocíticos do Plasmodium yoelii utilizando partículas Ty (retrotransposon de levedura), vírus recombinante e peptídeos sintéticos

Submitted by Gilvan Almeida ([email protected]) on 2017-04-10T17:41:10Z No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 72645.pdf: 432044355 bytes, checksum: 11e7a705f1b469e65a34dc9713696b4f (MD5)Approved for entry into archive by Raquel Dinelis ([email protected]) on 2017-10-24T17:27:59Z (GMT) No. of bitstreams: 2 72645.pdf: 432044355 bytes, checksum: 11e7a705f1b469e65a34dc9713696b4f (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2017-10-24T17:27:59Z (GMT). No. of bitstreams: 2 72645.pdf: 432044355 bytes, checksum: 11e7a705f1b469e65a34dc9713696b4f (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 1999Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilConsiderando que as células T CD8+ citotóxicas têm um papel importante na imunidade protetora contra a malária, nos propusemos a induzir uma resposta de células T CD8+ protetora contra os estágios pré-eritrocíticos do Plasmodium yoelii utilizando como imunógenos partículas Ty (retrotransposon de levedura), vírus vacínia recombinante e peptídeos sintéticos. A imunização com partículas Ty carreando um epitopo de células T CD8+ do P. yoelii (TyCS) foi capaz de induzir uma resposta de células T CD8+ específicas para a proteína CS entretanto, esta resposta só foi protetora quando os animais foram primados com as partículas Ty-CS e receberam uma segunda dose de vírus vacínia recombinante expressando a proteína CS de P. yoelii (VacCS). Esse esquema de imunização foi crucial para a indução de um número suficientemente grande de células T CD8+ específicas, para a inibição do desenvolvimento do parasita no fígado e para a proteção de 62% dos animais contra o desafio com esporozoítas Por outro lado, a imunização com o peptídeo sintético correspondente ao epitopo de células T CD8+ da proteína CS do P. yoelii induziu um pequeno número de células T CD8+ entretanto, quando este peptídeo foi inoculado junto com um peptídeo correspondente a um epitopo de células T CD4+ auxiliares da proteína CS ou da proteína de choque térmico do P. falciparum (Pf72/HSP70) a resposta pimária de células T CD8+ específicas para CS foi bastante aumentada. Além disso, a administração de uma segunda dose com o vírus recombinante VacCS nos animais primados com os peptídeos CD4+ e CD8+ potencializou a resposta primária. Esses dados mostram que as partículas Ty são um sistema promissor para vacinas que visam a indução de células T CD8+ e que a resposta de células T CD8+ induzida com peptídeos sintéticos pode ser potencializada pela adição de um epitopo de células T CD4+ no esquema de vacinação.In this work we studied the induction of protective CD8+ T cells against P. yoelii pre-erythrocytic stages using as immunogens Ty virus like particles (Ty-VLP), recombinant vaccinia virus (VacCS) and synthetic peptides. The immunization with Ty-VLP carrying the CD8+ T cell epitope of the circumsporozoite (TyCS) protein of P. yoelii induced specific CD8+ T cells. However, this response was not protective unless mice were primed with TyCS and boosted with VacCS. The sequence of immunization TyCS followed by VacCS was critical to generate a potent protective immune response, which inhibited strongly the development of liver stages of P. yoelii and protected 62% of mice from infection The immunization with the peptide corresponding to CD8+ T cell epitope of the CS protein of P. yoelii induced a low CD8+ T cell response. However, the administration of this peptide together with peptides corresponding to CD4+ T cell epitope of CS protein of P. yoelii or of P. falciparum heat shock protein (Pf72/HSP70), the response was enhanced. Mice primed with these CD8+ and CD4+ peptides also induced a potent secundary response when a booster with vaccinia recombinant expressing the P. yoelii CS protein was given. These data show that the Ty-VLP could be a promising vaccine delivery system to induce CD8+ T cells. Furthermore, the response of CD8+ T cells induced by synthetic peptides can be improved by the addiction of CD4+ T cell epitopes