Josue da Costa Lima Junior
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Scopus Publications
Fatima Conceição Silva, Paula Mello De Luca, and Josué da Costa Lima-Junior
MDPI AG
In the 18th century, English physician Edward Jenner laid the foundation for modern vaccination by achieving protection against variola [...]
Ada da Silva Matos, Isabela Ferreira Soares, Barbara de Oliveira Baptista, Hugo Amorim dos Santos de Souza, Lana Bitencourt Chaves, Daiana de Souza Perce-da-Silva, Evelyn Kety Pratt Riccio, Letusa Albrecht, Paulo Renato Rivas Totino, Rodrigo Nunes Rodrigues-da-Silva,et al.
MDPI AG
The PvCelTOS, PvCyRPA, and Pvs25 proteins play important roles during the three stages of the P. vivax lifecycle. In this study, we designed and expressed a P. vivax recombinant modular chimeric protein (PvRMC-1) composed of the main antigenic regions of these vaccine candidates. After structure modelling by prediction, the chimeric protein was expressed, and the antigenicity was assessed by IgM and IgG (total and subclass) ELISA in 301 naturally exposed individuals from the Brazilian Amazon. The recombinant protein was recognized by IgG (54%) and IgM (40%) antibodies in the studied individuals, confirming the natural immunogenicity of the epitopes that composed PvRMC-1 as its maintenance in the chimeric structure. Among responders, a predominant cytophilic response mediated by IgG1 (70%) and IgG3 (69%) was observed. IgM levels were inversely correlated with age and time of residence in endemic areas (p < 0.01). By contrast, the IgG and IgM reactivity indexes were positively correlated with each other, and both were inversely correlated with the time of the last malaria episode. Conclusions: The study demonstrates that PvRMC-1 was successfully expressed and targeted by natural antibodies, providing important insights into the construction of a multistage chimeric recombinant protein and the use of naturally acquired antibodies to validate the construction.
Bruno B. Loureiro, Paola Juber, Alessandra A. Souza, Edson M. Cezario, Josué C. Lima‐Junior, Karla Bianca F. C. Fontes, Isabela F. Soares, and Elizangela P. Zuza
Wiley
BACKGROUND
Ozone is a molecule that plays an important role in dentistry, specially for wound healing. The aim of the present study was to clinically and immunologically evaluate the effect of ozonated oil on the healing of palatal wounds.
METHODS
This is a prospective, longitudinal, triple-blind, randomized, placebo-controlled clinical trial. The groups were divided as follows: Test group (n = 14): after removal of the free gingival graft (FGG), the palatal wound was treated with ozonated sunflower oil with a peroxide index between 510 - 625 meq O2 /kg; Control group (n = 14): after removal of the FGG, the palatal wound was treated with non-ozonated sunflower oil (placebo). The treatments were applied three times a day, for seven days.
RESULTS
There were no significant differences in the measurements of wound area (mm2 ) between the test and control groups in the different periods evaluated (0, 3, 7, and 14 days; P>0.05). The intra-group analysis showed a significant decrease in wound size over the course of days (0, 3, 7, and 14 days; P<0.05). Vascular endothelial growth factor (VEGF; μg/mL) presented a significant reduction at 7 days (p<0.05) compared to day 3 in the test group (p<0.05). There was a statistical difference for malondialdehyde (MDA; μg/mL) in the test group between 3 and 7 days post-treatment (p<0.05) and between test and control groups on the 7th day (p<0.05).
CONCLUSIONS
The application of highly ozonated sunflower oil did not improve the remaining scar area of the palate, decreasing the VEGF and increasing the oxidative stress marker MDA. This article is protected by copyright. All rights reserved.
Rodrigo N. Rodrigues-da-Silva, Fernando P. Conte, Gustavo da Silva, Ana L. Carneiro-Alencar, Paula R. Gomes, Sergio N. Kuriyama, Antonio A. F. Neto, and Josué C. Lima-Junior
MDPI AG
The Nucleocapsid (N) protein is highlighted as the main target for COVID-19 diagnosis by antigen detection due to its abundance in circulation early during infection. However, the effects of the described mutations in the N protein epitopes and the efficacy of antigen testing across SARS-CoV-2 variants remain controversial and poorly understood. Here, we used immunoinformatics to identify five epitopes in the SARS-CoV-2 N protein (N(34–48), N(89–104), N(185–197), N(277–287), and N(378–390)) and validate their reactivity against samples from COVID-19 convalescent patients. All identified epitopes are fully conserved in the main SARS-CoV-2 variants and highly conserved with SARS-CoV. Moreover, the epitopes N(185–197) and N(277–287) are highly conserved with MERS-CoV, while the epitopes N(34–48), N(89–104), N(277–287), and N(378–390) are lowly conserved with common cold coronaviruses (229E, NL63, OC43, HKU1). These data are in accordance with the observed conservation of amino acids recognized by the antibodies 7R98, 7N0R, and 7CR5, which are conserved in the SARS-CoV-2 variants, SARS-CoV and MERS-CoV but lowly conserved in common cold coronaviruses. Therefore, we support the antigen tests as a scalable solution for the population-level diagnosis of SARS-CoV-2, but we highlight the need to verify the cross-reactivity of these tests against the common cold coronaviruses.
Edlainne Pinheiro Ferreira-Sena, Daiana de Jesus Hardoim, Flavia de Oliveira Cardoso, Luiz Ney d’Escoffier, Isabela Ferreira Soares, João Pedro Rangel da Silva Carvalho, Ricardo Almir Angnes, Stenio Perdigão Fragoso, Carlos Roberto Alves, Salvatore Giovanni De-Simone,et al.
MDPI AG
Leishmaniasis represents a complex of diseases with a broad clinical spectrum and epidemiological diversity, considered a major public health problem. Although there is treatment, there are still no vaccines for cutaneous leishmaniasis. Because Leishmania spp. is an intracellular protozoan with several escape mechanisms, a vaccine must provoke cellular and humoral immune responses. Previously, we identified the Leishmania homolog of receptors for activated C kinase (LACK) and phosphoenolpyruvate carboxykinase (PEPCK) proteins as strong immunogens and candidates for the development of a vaccine strategy. The present work focuses on the in silico prediction and characterization of antigenic epitopes that might interact with mice or human major histocompatibility complex class I. After immunogenicity prediction on the Immune Epitope Database (IEDB) and the Database of MHC Ligands and Peptide Motifs (SYFPEITHI), 26 peptides were selected for interaction assays with infected mouse lymphocytes by flow cytometry and ELISpot. This strategy identified nine antigenic peptides (pL1-H2, pPL3-H2, pL10-HLA, pP13-H2, pP14-H2, pP15-H2, pP16-H2, pP17-H2, pP18-H2, pP26-HLA), which are strong candidates for developing a peptide vaccine against leishmaniasis.
Barbara de Oliveira Baptista, Ana Beatriz Lopes de Souza, Luana Santos de Oliveira, Hugo Amorim dos Santos de Souza, Jenifer Peixoto de Barros, Lucas Tavares de Queiroz, Rodrigo Medeiros de Souza, Linda Eva Amoah, Susheel Kumar Singh, Michael Theisen,et al.
MDPI AG
The GMZ2.6c malaria vaccine candidate is a multi-stage P. falciparum chimeric protein that contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, an asexual-stage vaccine construction consisting of the N-terminal region of the glutamate-rich protein (GLURP) and the C-terminal region of the merozoite surface protein-3 (MSP-3). Previous studies showed that GMZ2.6c is widely recognized by antibodies from Brazilian exposed individuals and that its components are immunogenic in natural infection by P. falciparum. In addition, anti-GMZ2.6c antibodies increase with exposure to infection and may contribute to parasite immunity. Therefore, identifying epitopes of proteins recognized by antibodies may be an important tool for understanding protective immunity. Herein, we identify and validate the B-cell epitopes of GMZ2.6c as immunogenic and immunodominant in individuals exposed to malaria living in endemic areas of the Brazilian Amazon. Specific IgG antibodies and subclasses against MSP-3, GLURP, and Pfs48/45 epitopes were detected by ELISA using synthetic peptides corresponding to B-cell epitopes previously described for MSP-3 and GLURP or identified by BepiPred for Pfs48/45. The results showed that the immunodominant epitopes were P11 from GLURP and MSP-3c and DG210 from MSP-3. The IgG1 and IgG3 subclasses were preferentially induced against these epitopes, supporting previous studies that these proteins are targets for cytophilic antibodies, important for the acquisition of protective immunity. Most individuals presented detectable IgG antibodies against Pfs48/45a and/or Pfs48/45b, validating the prediction of linear B-cell epitopes. The higher frequency and antibody levels against different epitopes from GLURP, MSP-3, and Pfs48/45 provide additional information that may suggest the relevance of GMZ2.6c as a multi-stage malaria vaccine candidate.
Paola Juber, Bruno B. Loureiro, Elizangela P. Zuza, Edson M. Cezario, Rogério L. Romeiro, Josué C. Lima-Junior, Isabela F. Soares, and Alessandra A. Souza
Informa UK Limited
Barbara Oliveira Baptista, Ana Beatriz Lopes de Souza, Evelyn Kety Pratt Riccio, Cesare Bianco-Junior, Paulo Renato Rivas Totino, João Hermínio Martins da Silva, Michael Theisen, Susheel Kumar Singh, Linda Eva Amoah, Marcelo Ribeiro-Alves,et al.
Springer Science and Business Media LLC
AbstractBackgroundThe GMZ2.6c malaria vaccine candidate is a multi-stagePlasmodium falciparumchimeric protein which contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, a fusion protein of GLURP and MSP-3, that has been shown to be well tolerated, safe and immunogenic in clinical trials performed in a malaria-endemic area of Africa. However, there is no data available on the antigenicity or immunogenicity of GMZ2.6c in humans. Considering that circulating parasites can be genetically distinct in different malaria-endemic areas and that host genetic factors can influence the immune response to vaccine antigens, it is important to verify the antigenicity, immunogenicity and the possibility of associated protection in individuals living in malaria-endemic areas with different epidemiological scenarios. Herein, the profile of antibody response against GMZ2.6c and its components (MSP-3, GLURP and Pfs48/45) in residents of the Brazilian Amazon naturally exposed to malaria, in areas with different levels of transmission, was evaluated.MethodsThis study was performed using serum samples from 352 individuals from Cruzeiro do Sul and Mâncio Lima, in the state of Acre, and Guajará, in the state of Amazonas. Specific IgG, IgM, IgA and IgE antibodies and IgG subclasses were detected by Enzyme-Linked Immunosorbent Assay.ResultsThe results showed that GMZ2.6c protein was widely recognized by naturally acquired antibodies from individuals of the Brazilian endemic areas with different levels of transmission. The higher prevalence of individuals with antibodies against GMZ2.6c when compared to its individual components may suggest an additive effect of GLURP, MSP-3, and Pfs48/45 when inserted in a same construct. Furthermore, naturally malaria-exposed individuals predominantly had IgG1 and IgG3 cytophilic anti-GMZ2.6c antibodies, an important fact considering that the acquisition of anti-malaria protective immunity results from a delicate balance between cytophilic/non-cytophilic antibodies. Interestingly, anti-GMZ2.6c antibodies seem to increase with exposure to malaria infection and may contribute to parasite immunity.ConclusionsThe data showed that GMZ2.6c protein is widely recognized by naturally acquired antibodies from individuals living in malaria-endemic areas in Brazil and that these may contribute to parasite immunity. These data highlight the importance of GMZ2.6c as a candidate for an anti-malarial vaccine.
Tenzin Tashi, Aditi Upadhye, Prasun Kundu, Chunxiang Wu, Sébastien Menant, Roberta Reis Soares, Marcelo U. Ferreira, Rhea J. Longley, Ivo Mueller, Quyen Q. Hoang,et al.
Public Library of Science (PLoS)
Background To make progress towards malaria elimination, a highly effective vaccine targeting Plasmodium vivax is urgently needed. Evaluating the kinetics of natural antibody responses to vaccine candidate antigens after acute vivax malaria can inform the design of serological markers of exposure and vaccines. Methodology/Principal findings The responses of IgG antibodies to 9 P. vivax vaccine candidate antigens were evaluated in longitudinal serum samples from Brazilian individuals collected at the time of acute vivax malaria and 30, 60, and 180 days afterwards. Antigen-specific IgG correlations, seroprevalence, and half-lives were determined for each antigen using the longitudinal data. Antibody reactivities against Pv41 and PVX_081550 strongly correlated with each other at each of the four time points. The analysis identified robust responses in terms of magnitude and seroprevalence against Pv41 and PvGAMA at 30 and 60 days. Among the 8 P. vivax antigens demonstrating >50% seropositivity across all individuals, antibodies specific to PVX_081550 had the longest half-life (100 days; 95% CI, 83–130 days), followed by PvRBP2b (91 days; 95% CI, 76–110 days) and Pv12 (82 days; 95% CI, 64–110 days). Conclusion/Significance This study provides an in-depth assessment of the kinetics of antibody responses to key vaccine candidate antigens in Brazilians with acute vivax malaria. Follow-up studies are needed to determine whether the longer-lived antibody responses induced by natural infection are effective in controlling blood-stage infection and mediating clinical protection.
Barbara Bruno Fagundes Marques, Taísa Coelho Guimarães, Ricardo Guimarães Fischer, Justine Monteiro Monnerat Tinoco, Fábio Ramoa Pires, Josué da Costa Lima Junior, Roy H. Stevens, and Eduardo Muniz Barretto Tinoco
Wiley
Abstract Objective The aim of the present case–control study was to evaluate the morphological aspects of the epithelial cells from the dorsum of the tongue and the expression of the SARS‐CoV‐2 Spike protein in these cells, in patients with and without COVID‐19 infection. Methods 24 individuals with at least one symptom of COVID‐19 were recruited among inpatients from Hospital Universitário Pedro Ernesto (Rio de Janeiro, Brazil). 14 patients who tested positive for COVID‐19 by RT‐PCR were included in the case group, and 10 patients who tested negative were included in the control group. Cytological smears from the dorsum of the tongue were obtained from all patients and analyzed using immunohistochemistry directed against SARS‐CoV‐2‐Spike protein. Morphological changes in epithelial cells were analyzed using light microscopy. Results Immunohistochemistry showed that 71% of the COVID‐19 patients presented epithelial cells positive for the presence of the SARS‐CoV‐2 Spike protein, and all cells coming from patients in the control group were negative. Cytological analysis showed significant differences when comparing epithelial cells from COVID‐19‐positive and COVID‐19‐negative patients. Conclusion COVID‐19 may generate dimensional changes in tongue epithelial cells; however, further studies are necessary to understand how this happens.
Denis Bourgeois, Lucio Souza Gonçalves, Josué da Costa Lima-Junior, and Florence Carrouel
Frontiers Media SA
Lana Bitencourt Chaves, Glaucia de Oliveira Guimarães, Daiana de Souza Perce-da-Silva, Dalma Maria Banic, Paulo Renato Rivas Totino, Ricardo Luiz Dantas Machado, Rodrigo Nunes Rodrigues-da-Silva, Lilian Rose Pratt-Riccio, Cláudio Tadeu Daniel-Ribeiro, and Josué da Costa Lima-Junior
MDPI AG
The Plasmodium vivax Cysteine-Rich Protective Antigen (PvCyRPA) has an important role in erythrocyte invasion and has been considered a target for vivax malaria vaccine development. Nonetheless, its genetic diversity remains uncharted in Brazilian malaria-endemic areas. Therefore, we investigated the pvcyrpa genetic polymorphism in 98 field isolates from the Brazilian Amazon and its impact on the antigenicity of predicted B-cell epitopes. Genetic diversity parameters, population genetic analysis, neutrality test and the median-joining network were analyzed, and the potential amino acid polymorphism participation in B-cell epitopes was investigated. One synonymous and 26 non-synonymous substitutions defined fifty haplotypes. The nucleotide diversity and Tajima’s D values varied across the coding gene. The exon-1 sequence had greater diversity than those of exon-2. Concerning the prediction analysis, seven sequences were predicted as linear B cell epitopes, the majority contained in conformational epitopes. Moreover, important amino acid polymorphism was detected in regions predicted to contain residues participating in B-cell epitopes. Our data suggest that the pvcyrpa gene presents a moderate polymorphism in the studied isolates and such polymorphisms alter amino acid sequences contained in potential B cell epitopes, an important observation considering the antigen potentiality as a vaccine candidate to cover distinct P. vivax endemic areas worldwide.
Sílvia da Silva Fontes, Fernanda de Moraes Maia, Laura Santa’Anna Ataides, Fernando Paiva Conte, Josué da Costa Lima-Junior, Tatiana Rozental, Matheus Ribeiro da Silva Assis, Adonai Alvino Pessoa Júnior, Jorlan Fernandes, Elba Regina Sampaio de Lemos,et al.
MDPI AG
Coxiella burnetii is a global, highly infectious intracellular bacterium, able to infect a wide range of hosts and to persist for months in the environment. It is the etiological agent of Q fever—a zoonosis of global priority. Currently, there are no national surveillance data on C. burnetii’s seroprevalence for any South American country, reinforcing the necessity of developing novel and inexpensive serological tools to monitor the prevalence of infections among humans and animals—especially cattle, goats, and sheep. In this study, we used immunoinformatics and computational biology tools to predict specific linear B-cell epitopes in three C. burnetii outer membrane proteins: OMP-H (CBU_0612), Com-1 (CBU_1910), and OMP-P1 (CBU_0311). Furthermore, predicted epitopes were tested by ELISA, as synthetic peptides, against samples of patients reactive to C. burnetii in indirect immunofluorescence assay, in order to evaluate their natural immunogenicity. In this way, two linear B-cell epitopes were identified in each studied protein (OMP-H(51–59), OMP-H(91–106), Com-1(57–76), Com-1(191–206), OMP-P1(197–209), and OMP-P1(215–227)); all of them were confirmed as naturally immunogenic by the presence of specific antibodies in 77% of studied patients against at least one of the identified epitopes. Remarkably, a higher frequency of endocarditis cases was observed among patients who presented an intense humoral response to OMP-H and Com-1 epitopes. These data confirm that immunoinformatics applied to the identification of specific B-cell epitopes can be an effective strategy to improve and accelerate the development of surveillance tools against neglected diseases.
Otto Castro Nogueira, Mariana Gandini, Natasha Cabral, Vilma de Figueiredo, Rodrigo Nunes Rodrigues-da-Silva, Josué da Costa Lima-Junior, Roberta Olmo Pinheiro, Geraldo Moura Batista Pereira, Maria Cristina Vidal Pessolani, and Cristiana Santos de Macedo
Frontiers Media SA
Despite being treatable, leprosy still represents a major public health problem, and many mechanisms that drive leprosy immunopathogenesis still need to be elucidated. B cells play important roles in immune defense, being classified in different subgroups that present distinct roles in the immune response. Here, the profile of B cell subpopulations in peripheral blood of patients with paucibacillary (TT/BT), multibacillary (LL/BL) and erythema nodosum leprosum was analyzed. B cell subpopulations (memory, transition, plasmablasts, and mature B cells) and levels of IgG were analyzed by flow cytometry and ELISA, respectively. It was observed that Mycobacterium leprae infection can alter the proportions of B cell subpopulations (increase of mature and decrease of memory B cells) in patients affected by leprosy. This modulation is associated with an increase in total IgG and the patient’s clinical condition. Circulating B cells may be acting in the modulation of the immune response in patients with various forms of leprosy, which may reflect the patient’s ability to respond to M. leprae.
Artur A. M. L. Brandt, Rodrigo N. Rodrigues-da-Silva, Josué C. Lima-Junior, Carlos R. Alves, and Franklin de Souza-Silva
Hindawi Limited
Peptide TT830-843 from the tetanus toxin is a universal T-cell epitope. It helps in vaccination and induces T-cell activation. However, the fine molecular interaction between this antigen and the major histocompatibility complex (MHC) remains unknown. Molecular analysis of its interaction with murine MHC (H-2) was proposed to explore its immune response efficiency. Molecular dynamics simulations are important mechanisms for understanding the basis of protein-ligand interactions, and metadynamics is a useful technique for enhancing sampling in molecular dynamics. SPR (surface plasmon resonance) assays were used to validate whether the metadynamics results are in accordance with the experimental results. The peptide TT830-843 unbinding process was simulated, and the free energy surface reconstruction revealed a detailed conformational landscape. The simulation described the exiting path as a stepwise mechanism between progressive detachment states. We pointed out how the terminus regions act as anchors for binding and how the detachment mechanism includes the opening of α-helices to permit the peptide’s central region dissociation. The results indicated the peptide/H-2 receptor encounter occurs within a distance lesser than 27.5 Å, and the encounter can evolve to form a stable complex. SPR assays confirmed the complex peptide/H-2 as a thermodynamically stable system, exhibiting enough free energy to interact with TCR on the antigen-presenting cell surface. Therefore, combining in silico and in vitro assays provided significant evidence to support the peptide/H-2 complex formation.
Hugo Amorim dos Santos de Souza, Victor Fernandes Escafa, Carolina Moreira Blanco, Bárbara de Oliveira Baptista, Jenifer Peixoto de Barros, Evelyn Ketty Pratt Riccio, Aline Beatriz Mello Rodrigues, Gisely Cardoso de Melo, Marcus Vinícius Guimarães de Lacerda, Rodrigo Medeiros de Souza,et al.
FapUNIFESP (SciELO)
In the present study, we investigated the genetic diversity of Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain in two municipalities of the main malaria hotspot in Brazil, i.e., the Juruá Valley, and observed complete sequence identity among all P. vivax field isolates and the Sal-1 reference strain. Analysis of PvMCA1 catalytic domain in different P. vivax genomic sequences publicly available also revealed a high degree of conservation worldwide, with very few amino acid substitutions that were not related to putative histidine and cysteine catalytic residues, whose involvement with the active site of protease was herein predicted by molecular modeling. The genetic conservation presented by PvMCA1 may contribute to its eligibility as a druggable target candidate in vivax malaria.
Isabela Ferreira Soares, César López-Camacho, Rodrigo Nunes Rodrigues-da-Silva, Ada da Silva Matos, Barbara de Oliveira Baptista, Paulo Renato Rivas Totino, Rodrigo Medeiros de Souza, Kate Harrison, Alba Marina Gimenez, Elisângela Oliveira de Freitas,et al.
Springer Science and Business Media LLC
AbstractCircumsporozoite 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.
Roberta Reis Soares, Clovis Ryuichi Nakaie, Rodrigo Nunes Rodrigues‐da‐Silva, Rogério Lauria Silva, Josué da Costa Lima‐Junior, and Kézia Katiani Gorza Scopel
Wiley
Although antibodies are considered critical for malaria protection, little is known about the mechanisms/factors that maintain humoral immunity, especially regarding the induction and maintenance of memory B cells over time. In Brazilian endemic areas, this is the first time that the profile of antibody responses and the occurrence of antigen‐specific memory B cells (MBC) against P vivax were investigated during acute malaria and up to six months after parasite clearance. For this, we selected two peptides, PvAMA‐1(S290‐K307) and PvMSP‐9(E795‐A808), which represent the apical membrane antigen‐1 and merozoite surface protein‐9 of P vivax, respectively. Both peptides were previously described as containing linear B‐cell epitopes. Our findings were as follows: 1—both peptides were recognized by IgG antibodies at a high frequency (between 24% and 81%) in all study groups; 2—in the absence of infection, the IgG levels remained stable throughout 6 months of follow‐up; and 3—PvAMA‐1(S290‐K307) and PvMSP‐9(E795‐A808)‐specific MBCs were detected in all individual groups in the absence of reinfection throughout the follow‐up period, suggesting long‐lived MBC. However, no positive association was observed between malaria‐specific antibody levels and frequency of MBCs over time. Taken together, these results suggest that peptides can be, in the future, an alternative strategy to polypeptidic vaccine formulation.
Ada da Silva Matos, Rodrigo Nunes Rodrigues-da-Silva, Isabela Ferreira Soares, Barbara de Oliveira Baptista, Rodrigo Medeiros de Souza, Lana Bitencourt-Chaves, Paulo Renato Rivas Totino, Juan Camilo Sánchez-Arcila, Cláudio Tadeu Daniel-Ribeiro, César López-Camacho,et al.
Frontiers Media SA
Thrombospondin-related adhesive protein (TRAP) is essential for sporozoite motility and the invasion of mosquitoes' salivary gland and vertebrate's hepatocyte and is, thus, considered a promising pre-erythrocytic vaccine candidate. Despite the existence of a few reports on naturally acquired immune response against Plasmodium vivax TRAP (PvTRAP), it has never been explored so far in the Amazon region, so results are conflicting. Here, we characterized the (IgG and IgG subclass) antibody reactivity against recombinant PvTRAP in a cross-sectional study of 299 individuals exposed to malaria infection in three municipalities (Cruzeiro do Sul, Mâncio Lima and Guajará) from the Acre state of the Brazilian Amazon. In addition, the full PvTRAP sequence was screened for B-cell epitopes using in silico and in vitro approaches. Firstly, we confirmed that PvTRAP is naturally immunogenic in the cohort population since 49% of the individuals were IgG-responders to it. The observed immune responses were mainly driven by cytophilic IgG1 over all other sublcasses and the IgG levels that was corelated with age and time of residence in the studied area (p < 0.05). Interestingly, only the levels of specific anti-TRAP IgG3 seemed to be associated with protection, as IgG3 responders presented a significantly higher time elapse since the last malaria episode than those recorded for IgG3 non-responders. Regarding the B-cell epitope mapping, among the 148 responders to PvTRAP, four predicted epitopes were confirmed by recognition of antibodies (PvTRAPR197−H227; PvTRAPE237−T258; PvTRAPP344−G374; and PvTRAPE439−K454). Nevertheless, the frequency of responders against these peptides were low and did not show a clear correlation with the antibody response against the corresponding antigen. Moreover, none of the linear confirmed epitopes were located in the binding regions of PvTRAP in respect to the host cell ligand. Collectively, our data confirm the PvTRAP immunogenicity among Amazon inhabitants, while suggesting that the main important B-cell epitopes are not linear.
Lana Bitencourt Chaves, Daiana de Souza Perce-da-Silva, Paulo Renato Rivas Totino, Evelyn Kety Pratt Riccio, Barbara de Oliveira Baptista, Ana Beatriz Lopes de Souza, Rodrigo Nunes Rodrigues-da-Silva, Ricardo Luiz Dantas Machado, Rodrigo Medeiros de Souza, Cláudio Tadeu Daniel-Ribeiro,et al.
Elsevier BV
Lilian Rose Pratt-Riccio, Bárbara de Oliveira Baptista, Vanessa Rodrigues Torres, Cesare Bianco-Junior, Daiana de Souza Perce-Da-Silva, Evelyn Kety Pratt Riccio, Josué da Costa Lima-Junior, Paulo Renato Rivas Totino, Gustavo Capatti Cassiano, Luciane Moreno Storti-Melo,et al.
FapUNIFESP (SciELO)
BACKGROUND The central repetitive region (CRR) of the Plasmodium vivax circumsporozoite surface protein (CSP) is composed of a repetitive sequence that is characterised by three variants: VK210, VK247 and P. vivax-like. The most important challenge in the treatment of P. vivax infection is the possibility of differential response based on the parasite genotype. OBJECTIVES To characterise the CSP variants in P. vivax isolates from individuals residing in a malaria-endemic region in Brazil and to profile these variants based on sensitivity to chloroquine and mefloquine. METHODS The CSP variants were determined by sequencing and the sensitivity of the P. vivax isolates to chloroquine and mefloquine was determined by Deli-test. FINDINGS Although five different allele sizes were amplified, the sequencing results showed that all of the isolates belonged to the VK210 variant. However, we observed substantial genetic diversity in the CRR, resulting in the identification of 10 different VK210 subtypes. The frequency of isolates that were resistant to chloroquine and mefloquine was 11.8 and 23.8%, respectively. However, we did not observe any difference in the frequency of the resistant isolates belonging to the VK210 subtypes. MAIN CONCLUSION The VK210 variant is the most frequently observed in the studied region and there is significant genetic variability in the CRR of the P. vivax CSP. Moreover, the antimalarial drug sensitivity profiles of the isolates does not seem to be related to the VK210 subtypes.
Rodrigo Nunes Rodrigues-da-Silva, Daniely Correa-Moreira, Isabela Ferreira Soares, Paula Melo de-Luca, Paulo Renato Rivas Totino, Fernanda Nazaré Morgado, Maria das Graças de Oliveira Henriques, André Luis Peixoto Candea, Balwan Singh, Mary R. Galinski,et al.
Elsevier BV
Roberta Reis Soares, Clarissa F. Cunha, Raquel Ferraz‐Nogueira, Alessandro Marins‐dos‐Santos, Rodrigo Nunes Rodrigues‐da‐Silva, Irene Soares, Josué Lima‐Junior, Alvaro Luiz Bertho, Marcelo Urbano Ferreira, and Kézia Katiani Gorza Scopel
Wiley
Plasmodium falciparum‐specific antibodies tend to be short‐lived, but their cognate memory B cells (MBCs) circulate in the peripheral blood of exposed subjects for several months or years after the last infection. However, the time course of antigen‐specific antibodies and B‐cell responses to the relatively neglected parasite Plasmodium vivax remains largely unexplored. Here, we showed that uncomplicated vivax malaria elicits short‐lived antibodies but long‐lived MBC responses to a major blood‐stage P vivax antigen, apical membrane protein 1 (PvAMA‐1), in subjects exposed to declining malaria transmission in the Amazon Basin of Brazil. We found that atypical (CD19+CD10−CD21−CD27−) MBCs, which appear to share a common precursor with classical MBCs but are unable to differentiate into antibody‐secreting cells, significantly outnumbered classical MBCs by 5:1 in the peripheral blood of adult subjects currently or recently infected with P vivax and by 3:1 in healthy residents in the same endemic communities. We concluded that malaria can drive classical MBCs to differentiate into functionally impaired MBCs not only in subjects repeatedly exposed to P falciparum, but also in subjects living in areas with low levels of P vivax transmission in the Amazon, leading to an impaired B‐cell memory that may affect both naturally acquired and vaccine‐induced immunity.
Monique Paiva Campos, Fabiano Borges Figueiredo, Fernanda Nazaré Morgado, Alinne Rangel dos Santos Renzetti, Sara Maria Marques de Souza, Sandro Antônio Pereira, Rodrigo Nunes Rodrigues-Da-Silva, Josué Da Costa Lima-Junior, and Paula Mello De Luca
Frontiers Media SA
[This corrects the article DOI: 10.3389/fimmu.2018.01690.].
Monique Paiva Campos, Fabiano Borges Figueiredo, Fernanda Nazaré Morgado, Alinne Rangel dos Santos Renzetti, Sara Maria Marques de Souza, Sandro Antônio Pereira, Rodrigo Nunes Rodrigues-Da-Silva, Josué Da Costa Lima-Junior, and Paula Mello De Luca
Frontiers Media SA
In Brazil, canine visceral leishmaniasis (CVL) is caused by Leishmania infantum, presenting a broad spectrum of clinical manifestations. Dogs are the main parasite reservoir in urban areas and canine cases precede human infection. Currently, A2 protein based Leish-Tec® vaccine is the only vaccine commercially available against CVL in Brazil. Considering that the main screening and confirmatory tests of canine infection are serological, it is possible that the antibody response elicited after vaccination interfere with diagnosis, leading to the inability to distinguish between vaccinated and infected animals. In order to identify the specific B-cell response induced after vaccination, A2 protein sequence was screened for main linear B-cell epitopes using in silico prediction (Bepipred) and immunological confirmation by ELISA. Three amino acid sequences were described as potential B-cell epitopes (SV11-SAEPHKAAVDV, PP16-PQSVGPLSVGPQSVGP, and VQ34-VGPLSVGPQSVGPLSVGPLSVGPQAVGPLSVGPQ). Specific IgG ELISAs were performed in sera of 12 immunized dogs living in non-endemic areas, followed for up to 1 year after immunization. The results were compared with those obtained in a group of 10 symptomatic and 10 asymptomatic CVL dogs. All predicted epitopes were confirmed as linear B-cell epitopes broadly recognized by sera from studied dogs. Total IgG ELISAs demonstrated distinct patterns of response between peptides in the immunized and CVL groups. VQ34 peptide was recognized by the majority of sera from vaccinated and symptomatic dogs, and increases after vaccination. PP16 induced low levels of specific IgG that increased 1 year after immunization. Interestingly, a low frequency of reactivity was found against SV11 in naturally infected dogs (symptomatic and asymptomatic), while 83.3% of vaccinated dogs presented positive responses 1 year after immunization. The two animals in the vaccinated group that did not respond to SV11 1 year after immunization presented positive serology both 30 days and 6 months after immunization. In summary, we identified three main linear B-cell epitopes in A2 based vaccine. Moreover, the humoral response against SV11 presented marked differences between infected and Leish-Tec vaccinated dogs, and should be further investigated, in large trials, to confirm its potential as a serological marker able to distinguish between infected and vaccinated dogs.