Publications by authors named "Adeliane Castro da Costa"

13 Publications

  • Page 1 of 1

Larvicidal potential of cell wall degrading enzymes from Trichoderma asperellum against Aedes aegypti (Diptera: Culicidae).

Biotechnol Prog 2021 Jun 11:e3182. Epub 2021 Jun 11.

Laboratório de Química de Polímeros (LQP) - ICB2, Universidade Federal de Goiás, Goiânia, Brazil.

Aedes aegypti is a mosquito vector of arboviruses such as dengue, chikungunya, zika and yellow fever that cause important public health diseases. The incidence and gravity of these diseases justifies the search for effective measures to reduce the presence of this vector in the environment. Bioinsecticides are an effective alternative method for insect control, with added ecological benefits such as biodegradability. The current study demonstrates that a chitinolytic enzyme complex produced by the fungus Trichoderma asperellum can disrupt cuticle formation in the L3 larvae phase of A. aegypti, suggesting such biolarvicidal action could be used for mosquito control. T. asperellum was exposed to chitin from different sources. This induction of cell wall degrading enzymes, including chitinase, N-acetylglucosaminidase and β-1,3-glucanase. Groups of 20 L3 larvae of A. aegypti were exposed to varying concentrations of chitinolytic enzymes induced with commercial chitin (CWDE) and larvae cell wall degrading enzymes (L-CWDE). After 72 h of exposure to the CWDE, 100% of larvae were killed. The same percent mortality was observed after 48 h of exposure to L-CWDE at half the CWDE enzyme mixture concentration. Exoskeleton deterioration was further observed by scanning and electron microscopy. Our findings indicate that L-CWDE produced by T. asperellum reflect chitinolytic enzymes with greater specificity for L3 larval biomolecules. This specificity is characterized by the high percentage of mortality compared with CWDE treatments and also by abrupt changes in patterns of the cellular structures visualized by scanning and transmission electron microscopy. These mixtures of chitinolytic enzymes could be candidates, as adjuvant or synergistic molecules, to replace conventional chemical insecticides currently in use.
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http://dx.doi.org/10.1002/btpr.3182DOI Listing
June 2021

BCG revaccination of health workers in Brazil to improve innate immune responses against COVID-19: A structured summary of a study protocol for a randomised controlled trial.

Trials 2020 Oct 26;21(1):881. Epub 2020 Oct 26.

Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Goiás, Brazil.

Objectives: The BCG vaccine, widely used in Brazil in new-borns, induces adjuvant protection for several diseases, including childhood virus infections. BCG activates monocytes and innate memory NK cells which are crucial for the antiviral immune response. Therefore, strategies to prevent COVID-19 in health workers (HW) should be carried out to prevent them becoming unwell so that they can continue to work during the pandemic. The hypothesis is that BCG will improve the innate immune response and prevent symptomatic infection or COVID-19 severity. The primary objective is to verify the effectiveness and safety of the BCG vaccine to prevent or reduce incidence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the city of Goiânia (Brazil) among HW previously vaccinated with BCG and also its severity and mortality during the pandemic of the disease. Secondary objectives are to estimate the incidence of COVID-19 among these professionals and the innate immune response elicited to BCG.

Trial Design: This a phase II trial for repositioning BCG as a preventive strategy against COVID-19. The trial is an open-label, parallel-group randomised clinical trial, comparing HW vaccinated with BCG and HW not vaccinated.

Participants: The trial will recruit 800 HW of Goiânia - Goiás, Brazil to reach a total of 400 HW included after comorbidities questioning and laboratorial evaluation. Eligibility criteria: Any HW presenting BCG vaccination scar with direct contact with suspected COVID-19 patients for at least 8 hours per week, whether in hospital beds, ICU, or in transportation or admission (nurses, doctors, physiotherapists, nutritionists, receptionists, etc.) who have negative IgM and IgG COVID-19 test. Participants with any of the following characteristics will be excluded: - Have had in the last fifteen days any signs or symptoms of virus infection, including COVID-19; - Have had fever in the last fifteen days; - Have been vaccinated fifteen days before the inclusion; - Have a history or confirmation of any immunosuppressive disease such as HIV, presented solid tumour in the last two years or autoimmune diseases; - Are under preventive medication with antibiotics, steroid anti-inflammatories, or chemotherapy; - Have less than 500 neutrophils per mL of blood; - Have previously been diagnosed with tuberculosis; - Are breastfeeding or pregnant; - Are younger than 18 years old; - Are participating as an investigator in this clinical trial.

Intervention And Comparator: HW will be randomized into the BCG vaccinated group or the BCG unvaccinated control group. The BCG vaccinated group will receive in the right arm, intradermally, a one off dose of 0.1 mL corresponding to approximately 2 x10 to 8 x10 CFU of live, freeze-dried, attenuated BCG Moscow 361-I, Bacillus Calmette Guerin vaccine (Serum Institute of India PVT. LTD.). The unvaccinated control group will not be vaccinated. The HW allocated in both groups will be followed up at specific times points until 180 days post inclusion. The vaccinated and control groups will be compared according to COVID-19 related outcomes.

Main Outcomes: The primary outcomes are the incidence coefficient of infection by SARS-CoV-2 determined by RT-PCR of naso-oropharyngeal swab specimen or rapid lateral flow IgG and IgM test, and presence of general COVID-19 symptoms, disease severity and admission to hospital during the 180 days of follow up. The secondary outcome is the innate immune response elicited 15-20 days after vaccination.

Randomisation: The vaccine vial contains approximately 10 doses. In order to optimize the vaccine use, the randomisation was performed in blocks of 20 participants using the platform randomization.com [ http://www.jerrydallal.com/random/permute.htm ]. The randomization was prepared before any HW inclusion. The results were printed and inserted in sealed envelopes that were numbered with BCG-001 to BCG-400. The printed results as well the envelopes had the same numbers. At the time of the randomisation, each participant that meets the inclusion criteria will receive a consecutive participant number [BCG-001-BCG-400]. The sealed envelope with the assigned number, blinded to the researchers, will be opened in front of the participant and the arm allocation will be known.

Blinding (masking): There is no masking for the participants or for the healthcare providers. The study will be blinded to the laboratory researchers and to those who will be evaluating the outcomes and performing the statistical analyses. In this case, only the participant identification number will be available.

Numbers To Be Randomised (sample Size): Four hundred heath workers will be randomised in two groups. Two hundred participants will be vaccinated, and 200 participants will not be vaccinated.

Trial Status: The protocol approved by the Brazilian Ethical Committee is the seventh version, number CAAE: 31783720.0.0000.5078. The trial has been recruiting since September 20, 2020. The clinical trial protocol was registered on August 5, 2020. It is estimated that recruitment will finish by March 2021.

Trial Registration: The protocol number was registered on August 5, 2020 at REBEC (Registro Brasileiro de Ensaios Clínicos). Register number: RBR-4kjqtg and WHO trial registration number UTN: U1111-1256-3892.

Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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http://dx.doi.org/10.1186/s13063-020-04822-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586662PMC
October 2020

The Gene from subsp.  is Related to Siderophore Synthesis.

Indian J Microbiol 2019 Jun 27;59(2):180-187. Epub 2019 Feb 27.

Tropical Institute of Pathology and Public Health, Federal University of Goiás, Rua 235 esquina com 1a avenida S/N, Setor Universitário, Goiânia, Goiás CEP 7405-050 Brazil.

Iron (Fe) homeostasis control is important for both pathogen and the host. During infection, the host reduces the access of microorganisms to iron, however, studies have shown that virulent pathogens are capable to sequester Fe from host proteins, and establish the infection. subsp. (Mycma), that is resistant to most drugs used against tuberculosis, was responsible for outbreaks around the world showing increased virulence when compared to other rapidly growing mycobacteria. The goal of this study was to determine whether Mycma produce siderophores and if the gene expression, a putative homolog of gene located in the gene cluster, is related to the synthesis of these molecules. For that, the effect of different iron concentrations on the growth of Mycma, the expression of gene, and the production of siderophores was evaluated in vitro and in vivo. It is shown that Mycma produce siderophores under iron deprivation conditions and gene expression was influenced by iron availability. The gene expression was also increased after macrophage or in vivo infection indicating that mycobactin synthesis by Mycma could participate in the Fe sequestration from the host during infection. In conclusion, we show that Mycma produces siderophores under iron deprivation conditions and that the gene is involved in this process, furthermore, this gene expression is induced during infection.
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http://dx.doi.org/10.1007/s12088-019-00788-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458192PMC
June 2019

Non-classical circulating monocytes in severe obesity and obesity with uncontrolled diabetes: A comparison with tuberculosis and healthy individuals.

Tuberculosis (Edinb) 2019 01 5;114:30-41. Epub 2018 Nov 5.

Laboratório de Imunopatologia das Doenças Infecciosas, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Rua 235, Setor Universitário, Goiânia, Goiás, CEP 74605050 Brazil. Electronic address:

Severe obesity and diabetes lead to a significant decrease in quality of life. Although controversial, population-wide studies have implicated obesity in the development of tuberculosis (TB). Non-classical monocytes have been described in obesity and TB, whereas in diabetes they have been associated with poorer clinical outcomes. The present study focuses on the functional significance of several monocyte populations of obese, obesity-related diabetic (OBDM), non-obese/diabetic tuberculosis and non-obese healthy control patients. Monocytes were evaluated by measuring expression of CD86, CD206, TLR-2 and TLR-4 as well as production of IL-6, IL-12, and by using a mycobacterial growth inhibition assay for both Mycobacterium tuberculosis and M. abscessus subsp. massiliense. Non-classical monocytes from OBDM and non-obese TB patients exhibited similar activation profiles (CD86/CD206/TLR-2 and TLR-4 expressions). Only monocytes from TB patients had a higher positivity for IL-12 and IL-6, whereas adiponectin serum levels increased similarly between TB and OBDM patients. Monocytes from active TB patients and OBDM were more permissive to Mtb growth than obese individuals, but this susceptibility was not observed for M. abscessus subsp. massiliense. From these findings, we conclude that diabetes and tuberculosis had similarities in the population of circulating non-classical monocytes, improving our understanding of the association of these diseases.
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http://dx.doi.org/10.1016/j.tube.2018.11.003DOI Listing
January 2019

Specific T cell induction using iron oxide based nanoparticles as subunit vaccine adjuvant.

Hum Vaccin Immunother 2018 12;14(11):2786-2801. Epub 2018 Jul 12.

a Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás (IPTSP-UFG) , Brasil.

Metal-based nanoparticles (NPs) stimulate innate immunity; however, they have never been demonstrated to be capable of aiding the generation of specific cellular immune responses. Therefore, our objective was to evaluate whether iron oxide-based NPs have adjuvant properties in generating cellular Th1, Th17 and TCD8 (Tc1) immune responses. For this purpose, a fusion protein (CMX) composed of antigens was used as a subunit vaccine. Citrate-coated MnFeO NPs were synthesized by co-precipitation and evaluated by transmission electron microscopy. The vaccine was formulated by homogenizing NPs with the recombinant protein, and protein corona formation was determined by dynamic light scattering and field-emission scanning electron microscopy. The vaccine was evaluated for the best immunization route and strategy using subcutaneous and intranasal routes with 21-day intervals between immunizations. When administered subcutaneously, the vaccine generated specific CD4IFN-γ (Th1) and CD8IFN-γ responses. Intranasal vaccination induced specific Th1, Th17 (CD4IL-17) and Tc1 responses, mainly in the lungs. Finally, a mixed vaccination strategy (2 subcutaneous injections followed by one intranasal vaccination) induced a Th1 (in the spleen and lungs) and splenic Tc1 response but was not capable of inducing a Th17 response in the lungs. This study shows for the first time a subunit vaccine with iron oxide based NPs as an adjuvant that generated cellular immune responses (Th1, Th17 and TCD8), thereby exhibiting good adjuvant qualities. Additionally, the immune response generated by the subcutaneous administration of the vaccine diminished the bacterial load of Mtb challenged animals, showing the potential for further improvement as a vaccine against tuberculosis.
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http://dx.doi.org/10.1080/21645515.2018.1489192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314432PMC
July 2018

Identification of specific antibodies against the Ag85C-MPT51-HspX fusion protein (CMX) for serological screening of tuberculosis in endemic area.

Expert Rev Clin Immunol 2017 08 30;13(8):837-843. Epub 2017 Jun 30.

a Programa de Pós-graduação , Universidade Ceuma , São Luis , MA , Brazil.

Objectives: Development of new tools for rapid and accurate diagnosis of tuberculosis (TB) is considered a strategy for controlling the disease. The recombinant CMX fusion protein is composed of immunodominant epitopes of the Ag85C (Rv0129c), MPT51 (Rv3803c) and the entire HspX (Rv2031c) proteins from Mycobacterium tuberculosis H37Rv (Mtb). The aim of this study was to evaluate the applicability of a test using the CMX protein in individuals suspected of TB.

Methods: Indirect ELISA was used to measure serum anti-CMX IgM and IgG in individuals with pulmonary TB.

Results: Patients with pulmonary TB had higher titers of IgM (OD = 0.502 ± 0.281) than healthy controls (OD = 0.200 ± 0.125). The cutoff for IgM-ELISA was determined using ROC curve analyzes (AUC = 0.868) with a sensitivity of 80.1% and a specificity of 78.2%. Patients with pulmonary TB also had higher titers of IgG (OD = 0.525 ± 0.391) than healthy controls (OD = 0.215 ± 0.077). The cutoff for IgG-ELISA was determined using ROC curve analyzes (AUC = 0.864) with a sensitivity of 81.7% and a specificity of 74.7%.

Conclusion: The results suggest that the recombinant protein CMX can be used in a serological test to complement the screening of individuals suspected of having active pulmonary TB.
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http://dx.doi.org/10.1080/1744666X.2017.1345626DOI Listing
August 2017

Prevalence of chronic obstructive pulmonary disease among patients with systemic arterial hypertension without respiratory symptoms.

Int J Chron Obstruct Pulmon Dis 2015 31;10:1525-9. Epub 2015 Jul 31.

Faculdade de Medicina de Petrópolis/FASE, Petrópolis, Brazil ; Instituto de Doenças do Tórax da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Background: The diagnosis of chronic obstructive pulmonary disease (COPD) is often delayed until later stages of the disease. The purpose of the present study was to determine the prevalence of COPD among adults on treatment for systemic arterial hypertension independently of the presence of respiratory symptoms.

Methods: This cross-sectional study included adults aged ≥40 years with tobacco/occupational exposure and systemic arterial hypertension diagnosed at three Primary Health Care facilities in Goiania, Brazil. Patients were evaluated using a standardized respiratory questionnaire and spirometry. COPD prevalence was measured considering the value of forced vital capacity and/or forced expiratory volume in 1 second <0.70.

Results: Of a total of 570 subjects, 316 (55%) met inclusion criteria and were invited to participate. Two hundred and thirty-three (73.7%) patients with arterial hypertension reported at least one respiratory symptom, while 83 (26.3%) reported no respiratory symptoms; 41 (17.6%) patients with arterial hypertension and at least one respiratory symptom, and 10 (12%) patients with arterial hypertension but no respiratory symptoms were diagnosed with COPD (P=0.24). The prevalence of COPD in people with no previous COPD diagnosis was greater among those with no respiratory symptoms (100%) than among those with respiratory symptoms (56.1%) (P=0.01).

Conclusion: Our findings suggest that regardless of the presence of respiratory symptoms, individuals aged ≥40 years with tobacco/occupational exposure and arterial hypertension may benefit from spirometric evaluation.
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http://dx.doi.org/10.2147/COPD.S85588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527375PMC
April 2016

A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis.

PLoS One 2014 14;9(11):e112848. Epub 2014 Nov 14.

Laboratório de Imunopatologia das Doenças Infecciosas, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112848PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232451PMC
December 2015

Interleukin-6 and interleukin-8 blood levels' poor association with the severity and clinical profile of ex-smokers with COPD.

Int J Chron Obstruct Pulmon Dis 2014 29;9:735-43. Epub 2014 Jul 29.

Faculty of Medicine, Federal University of Goiás, Goiânia, Goiás, Brazil.

Background: The role of interleukins in the severity and clinical profile of chronic obstructive pulmonary disease (COPD) is not known, but evidence supports the contribution of systemic inflammation to disease pathophysiology. This study evaluated the relationship of serum biomarkers to the severity and clinical parameters of COPD.

Methods And Findings: Serum levels of high-sensitivity C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured in 50 patients with stable COPD and in 16 controls. The levels of these biomarkers were compared with parameters of severity, such as the grading of flow obstruction using the recommendations of the Global initiative for chronic Obstructive Lung Disease, the BMI (body mass index), obstruction, dyspnea, exercise capacity (health index) index, the number of exacerbations within the last year, and peripheral oxygen saturation after the six-minute walk test, and with clinical parameters, such as bronchitis and non-bronchitis phenotypes, the number of associated comorbidities, and the smoking burden. COPD patients exhibited higher levels of IL-6 and IL-8 compared to the control group. Higher levels of IL-6 occurred in COPD groups with body mass index <21 kg/m(2), with more than two exacerbations in the past year, with a higher smoking burden, and with bronchitis. The increase in serum IL-8 was found only in the group with the highest number of exacerbations within the previous year.

Conclusion: Increased IL-6 was mainly associated with smoking burden, in patients who had smoked for more than 30 pack-years and exhibited a bronchitis phenotype. No direct association was observed for both IL-6 and IL-8 blood levels with the severity of COPD in ex-smokers.
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http://dx.doi.org/10.2147/COPD.S64135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122580PMC
February 2015

Recombinant BCG: Innovations on an Old Vaccine. Scope of BCG Strains and Strategies to Improve Long-Lasting Memory.

Front Immunol 2014 7;5:152. Epub 2014 Apr 7.

Department of Microbiology, Immunology, Parasitology and Pathology, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás , Goiânia , Brazil.

Bacille Calmette-Guérin (BCG), an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB). Despite its protection against active TB in children, BCG has failed to protect adults against TB infection and active disease development, especially in developing countries where the disease is endemic. Currently, there is a significant effort toward the development of a new TB vaccine. This review article aims to address publications on recombinant BCG (rBCG) published in the last 5 years, to highlight the strategies used to develop rBCG, with a focus on the criteria used to improve immunological memory and protection compared with BCG. The literature review was done in April 2013, using the key words TB, rBCG vaccine, and memory. This review discusses the BCG strains and strategies currently used for the modification of BCG, including: overexpression of Mycobacterium tuberculosis (Mtb) immunodominant antigens already present in BCG; gene insertion of immunodominant antigens from Mtb absent in the BCG vaccine; combination of introduction and overexpression of genes that are lost during the attenuation process of BCG; BCG modifications for the induction of CD8+ T-cell immune responses and cytokines expressing rBCG. Among the vaccines discussed, VPM1002, also called rBCGΔureC:hly, is currently in human clinical trials. Much progress has been made in the effort to improve BCG, with some promising candidates, but considerable work is still required to address functional long-lasting memory.
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http://dx.doi.org/10.3389/fimmu.2014.00152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984997PMC
June 2014

Different phenotypes of CD8+ T cells associated with bacterial load in active tuberculosis.

Immunol Lett 2014 Jul 30;160(1):23-32. Epub 2014 Mar 30.

Department of Microbiology, Immunology, Parasitology and Pathology, Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, Goiás, Brazil. Electronic address:

Tuberculosis is an infectious disease that affects millions of people worldwide with an annual mortality rate of 1.3 million. The mechanisms contributing to the loss of balance of immune responses and progression to active tuberculosis disease are unknown. Although CD4+ and CD8+ T cells and the cytokines they produce are crucial for protection against tuberculosis they have different roles in tuberculosis immunology. The function of CD4+ T cells has been extensively studied; however, less is known about the phenotype and function of CD8+ T cells. This study evaluated the specific expression of IFN-γ, IL-17, IL-10, and TGF-β and ex vivo expression of perforin and granzyme-B by CD8+ T cells from active tuberculosis individuals compared with latent infected individuals and non-latent infected individuals. Tuberculosis responses were correlated with the baciloscopy score. We observed that the presence of IL-10 and TGF-β expression and down-expression of granzyme-B in CD8+ T cells correlated with increased sputum bacillary load in active tuberculosis individuals. These findings provide new insights into the role of CD8+ T cells in Mycobacterium tuberculosis disease.
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http://dx.doi.org/10.1016/j.imlet.2014.03.009DOI Listing
July 2014

Immunogenicity of a fusion protein containing immunodominant epitopes of Ag85C, MPT51, and HspX from Mycobacterium tuberculosis in mice and active TB infection.

PLoS One 2012 25;7(10):e47781. Epub 2012 Oct 25.

Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.

Tuberculosis (TB) remains a major global health problem. The only vaccine against tuberculosis, attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG), has demonstrated relatively low efficacy and does not provide satisfactory protection against the disease in adults. More effective vaccines and better therapies are urgently needed to reduce the global spread of TB. This study evaluated the immunogenicity of a recombinant M. tuberculosis Ag85C-MPT51-HspX fusion protein (CMX) in mice and individuals with active tuberculosis. BALB/c mice were immunized with the CMX protein liposome-encapsulated with CpG DNA or with CpGDNA liposome-encapsulated, liposome or saline as negative controls. The immunization produced high levels of anti-CMX -specific IgG1 and IgG2a antibodies and induced an increase in the relative and absolute numbers of specific TCD4 IFN-γ(+) and TNF-α(+) cells in the spleen. Sera from a cohort of individuals with active tuberculosis contained higher levels of IgG and IgM that recognized CMX when compared to healthy individuals. In conclusion, this protein was shown to be immunogenic both in mice and humans.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0047781PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485045PMC
May 2013