Positive Effects of Extra-Virgin Olive Oil Supplementation and DietBra on Inflammation and Glycemic Profiles in Adults With Type 2 Diabetes and Class II/III Obesity: A Randomized Clinical Trial

Background: Evidence on the effects of dietary interventions on inflammatory markers in individuals with obesity and type 2 diabetes mellitus (T2DM) is scarce. Our study evaluated the effects of extra-virgin olive oil alone and in combination with a traditional Brazilian diet on inflammatory markers and glycemic profiles in adults with both T2DM and class II/III obesity. Methods: Adults aged 18-64 years with T2DM and class II/III obesity were randomized into two intervention groups: 1) extra-virgin olive oil only and 2) extra-virgin olive oil + a traditional Brazilian diet (OliveOil+DietBra). Data on sociodemographic characteristics, lifestyle, anthropometry, biochemical markers and inflammatory markers were collected. The primary outcomes were glycemic parameters and inflammatory markers. The body mass index (BMI) and weight were the secondary outcomes. Results: Forty individuals with T2DM and class II/III obesity were enrolled, and 34 (85%) completed the intervention course. The intake of olive oil was 37.88 ± 12.50 mL/day in the olive oil group and 37.71 ± 12.23 mL/day in the OliveOil+DietBra group, with no significant difference between groups (p = 0.484). Compared to the olive oil only group, the OliveOil+DietBra group had significantly lower levels of fasting insulin (p = 0.047) at the end of the intervention, whereas the other glycemic parameters were not altered. In the OliveOil+DietBra group, serum levels of inflammatory cytokines, IL-1α (p = 0.006) and adiponectin (p = 0.049) were lower and those of TNFα were higher (p = 0.037). There was a significant reduction in BMI and weight compared to the baseline values in the OliveOil+DietBra group (p = 0.015). Conclusions: The intervention with OliveOil+DietBra effectively decreased the levels of fasting insulin, IL-1α and adiponectin, suggesting its beneficial role in improving the inflammatory profiles and fasting insulin levels in adults with class II/III obesity and T2DM. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT02463435

Evaluation of the immune response modulation induced by vaccine against tuberculosis: rBCG-CMX

Submitted by Cláudia Bueno ([email protected]) on 2016-05-11T20:41:59Z No. of bitstreams: 2 Tese - Adeliane Castro da Costa - 2016.pdf: 6997901 bytes, checksum: a6d453a5d3acafaed991fe945aa59330 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Luciana Ferreira ([email protected]) on 2016-05-12T10:41:03Z (GMT) No. of bitstreams: 2 Tese - Adeliane Castro da Costa - 2016.pdf: 6997901 bytes, checksum: a6d453a5d3acafaed991fe945aa59330 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2016-05-12T10:41:03Z (GMT). No. of bitstreams: 2 Tese - Adeliane Castro da Costa - 2016.pdf: 6997901 bytes, checksum: a6d453a5d3acafaed991fe945aa59330 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2016-03-01Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqIn the first chapter of this thesis we demonstrate, in a review article, some of the successful strategies employed in the construction of Bacillus Calmette-Guérin (BCG) vaccines, among others being: overexpression of promising Mycobacterium tuberculosis (Mtb) immunodominant antigens already expressed by BCG introduction of Mtb immunodominant antigens not expressed by BCG, such as antigens in the regions of difference (RD) 1 thru 16; combination of overexpression and introduction of novel antigens to BCG; BCG modification to skew immune response toward TCD8+, as for example recombinant BCG (rBCG) expressing cytokines. In the second chapter, we demonstrate that the recombinant fusion protein CMX is capable of aggregating important immunogenic properties to vaccine vectors, by inducing an effective response for the control of Mtb infection in the mouse tuberculosis infection model. It is hypothesized that the introduction of the rCMX protein in the BCG vaccine could add immunological properties that are absent in BCG, thus leading to the induction of important cell populations for the control of Mtb infection. Our results demonstrate that the introduction of the rCMX in the BCG vaccine, resulting the recombinant BCG vaccine (rBCG-CMX) was an important factor for the observed Th1 and Th17 responses, as well as polyfunctional cells, that could be responsible for the reduced inflammatory lesions seen in the lungs of Mtb infected BALB/c mice, significantly reducing the bacillary load in comparison to in comparison to mice immunized with BCG Moreau vaccine. Lastly, in the third chapter of this thesis we propose that rCMX protein could be responsible for modulating the BCG vaccine to activate a more adequate and protective innate immunity. Our results show that the rBCG-CMX vaccine induces the activation of alveolar macrophages by means of expression of activation-associated molecules CD86 and CD206. The increase in the expression of those molecules are accompanied by the production of TGF-β e IL-1α which in turn could be responsible for the decreased necrosis and higher apoptosis induction promoted by rBCG-CMX vaccination. This phenomenon could be providing a higher cellular survival rate of the recombinant vaccine, leading to a better processing and presentation by MHC-II. As rCMX was shown to induce the production of IL-1α, IL-6 e TGF-β by a pathway that seems to involve the participation of TLR-4, we hypothesize that this recombinant protein could be modulating the BCG vaccine to induce a more appropriate and protectiveresponse for Mtb infection.A Tuberculose (Tb) é uma doença infecto contagiosa, causada pelo Mycobacterium tuberculosis (Mtb). Apesar de ser uma doença antiga, a Tb continua sendo um dos principais problemas de saúde pública. A Organização Mundial de Saúde acredita que cerca de um terço da população mundial está infectado com Mtb, gerando milhões de mortes por ano. Uma das medidas que podem melhorar a prevenção e bloquear a transmissão do Mtb é o desenvolvimento de novas vacinas que previnam o estabelecimento e a progressão da TB em humanos. Embora exista a vacina BCG que é eficiente contra formas graves de TB na infância, existe a necessidade do desenvolvimento de novas vacinas para controlar a disseminação da TB, que sejam mais eficientes e seguras que a BCG. Com este intuito, o objetivo deste trabalho é avaliar a proteção e a modulação da resposta imune induzida por BCG recombinante expressando espítopos imunodominantes Ag85C, MPT-51 e HspX do Mycobacterium tuberculosis induzida em modelo murino. Nossos resultados demonstram que a inserção da proteína CMX na vacina BCG recombinante (rBCG-CMX) foi um fator determinante para indução de resposta Th1 e Th17, além de células polifuncionais que possivelmente foram responsáveis pela redução das lesões inflamatórias no pulmão de camundongos BALB/c, reduzindo significantemente a carga bacilar em comparação com imunização com BCG Moreau. Além disso mostramos neste trabalho que a proteína rCMX é capaz de modular a vacina BCG e ativar a imunidade inata para a indução de uma melhor resposta protetora. Nossos resultados demonstram que a vacina rBCG-CMX induz ativação de macrófagos pulmonares por meio da expressão de moléculas de ativação CD86 e CD206. O aumento da expressão dessas moléculas é acompanhada por produção de TGF-β e IL-1α, sendo prováveis responsáveis pela menor indução de necrose e maior indução de apoptose pela vacina rBCG-CMX. Este fenômeno pode estar proporcionando a esta vacina maior capacidade de sobrevivência celular, colaborando para um melhor processamento e apresentação por MHC-II. Devido a proteína rCMX ser capaz de induzir produção de IL-1α, IL-6 e TGF-β por uma via que parece haver a participação de TLR-4. In vivo demonstramos que a vacina rBCG-CMX depende de TLR-2 e TLR-4 para induzir respostas Th1 e Th17, após imunização de camundongos com esta vacina. Neste trabalho hipotetizamos que a proteína CMX pode modular a resposta imune inata e adaptativa, por uma via em que há a participação do TLR-4. Esta pode ser a via pela qual a CMX, quando expressa por BCG favorece uma boa resposta protetora em animais desafiados com Mtb

Recombinant BCG: innovations on an old vaccine. Scope of BCG strains and strategies to improve long-lasting memory

Submitted by Jaqueline Silva ([email protected]) on 2018-11-01T18:35:48Z No. of bitstreams: 2 Artigo - Adeliane Castro da Costa - 2014.pdf: 461993 bytes, checksum: d6bacb2d38d85ebaeed76b4cbdae2f0f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Rejected by Luciana Ferreira ([email protected]), reason: No Lattes o nome está : Ana Paula Junqueira-Kipnis on 2018-11-05T09:27:14Z (GMT)Submitted by Jaqueline Silva ([email protected]) on 2018-11-06T12:02:53Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Artigo - Adeliane Castro da Costa - 2014.pdf: 461993 bytes, checksum: d6bacb2d38d85ebaeed76b4cbdae2f0f (MD5)Approved for entry into archive by Luciana Ferreira ([email protected]) on 2018-11-07T09:55:04Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Artigo - Adeliane Castro da Costa - 2014.pdf: 461993 bytes, checksum: d6bacb2d38d85ebaeed76b4cbdae2f0f (MD5)Made available in DSpace on 2018-11-07T09:55:04Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Artigo - Adeliane Castro da Costa - 2014.pdf: 461993 bytes, checksum: d6bacb2d38d85ebaeed76b4cbdae2f0f (MD5) Previous issue date: 2014-04-07Bacille Calmette–Guérin (BCG), an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB). Despite its protection against activeTB in children, BCG has failed to protect adults againstTB 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 newTB 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 CD8CT-cell immune responses and cytokines expressing rBCG. Among the vaccines discussed,VPM1002, also called rBCGDureC: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

Decreased Expression of CD314 by NK Cells Correlates with Their Ability to Respond by Producing IFN-γ after BCG Moscow Vaccination and Is Associated with Distinct Early Immune Responses

The immune response to vaccines is complex and results in various outcomes. BCG vaccination induces innate and specific responses that can lead to protection against tuberculosis, and cross-protection against other infections. NK cells have been associated with BCG-induced protection. Therefore, we hypothesize that differences in NK cell status before BCG vaccination may have a role in the ability of BCG to activate the immune response. Participants of a clinical trial were evaluated after BCG vaccination. The participants were assigned to different groups according to variation in IFN-γ expression by NK cells between days 1 and 15 after BCG vaccination. Individuals that presented a higher increase in IFN-γ expression by NK cells presented reduced CD314 expression at day 1, and after vaccination an increase in inflammatory NK cells and CD4 T-cell expression of IL-17. A negative correlation between expression of CD314 at day 1 and that of IFN-γ by NK cells after BCG vaccination was observed. Participants with lower of IFN-γ expression by NK cells after BCG vaccination presented an increase in the cytotoxic NK subpopulation and CD4 T-cell expression of IL-17 and IFN-γ. In conclusion, the expression of CD314 by NK cells before BCG vaccination influences their IFN-γ responses, generation of NK subpopulations, and the specific T immune response at 15 days after vaccination

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

AbstractTuberculosis 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

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

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 Mycobacterium tuberculosis antigens was used as a subunit vaccine. Citrate-coated MnFe2O4 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 CD4+IFN-γ+ (Th1) and CD8+IFN-γ+ responses. Intranasal vaccination induced specific Th1, Th17 (CD4+IL-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

Immunogenicity of a Fusion Protein Containing Immunodominant Epitopes of Ag85C, MPT51, and HspX from <em>Mycobacterium tuberculosis</em> in Mice and Active TB Infection

<div><p>Tuberculosis (TB) remains a major global health problem. The only vaccine against tuberculosis, attenuated <em>Mycobacterium bovis</em> 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 <em>M. tuberculosis</em> 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.</p> </div