9 research outputs found

    Cellular and Humoral Responses Follow-up for 8 Months after Vaccination with mRNA-Based Anti-SARS-CoV-2 Vaccines

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    Vaccination against SARS-CoV-2 has become the main method of reducing mortality and severity of COVID-19. This work aims to study the evolution of the cellular and humoral responses conferred by two mRNA vaccines after two doses against SARS-CoV-2. On days 30 and 240 after the second dose of both vaccines, the anti-S antibodies in plasma were evaluated from 82 volunteers vaccinated with BNT162b2 and 68 vaccinated with mRNA-1273. Peripheral blood was stimulated with peptides encompassing the entire SARS-CoV-2 Spike sequence. IgG Anti-S antibodies (humoral) were quantified on plasma, and inflammatory cytokines (cellular) were measured after stimulation. We observed a higher response (both humoral and cellular) with the mRNA-1273 vaccine. Stratifying by age and gender, differences between vaccines were observed, especially in women under 48 and men over 48 years old. Therefore, this work could help to set up a vaccination strategy that could be applied to confer maximum immunity.This work was partially supported by grants from the Instituto de Salud Carlos III (ISCIII) (PI18/00506; COV20/00063), co-funded by ERDF (FEDER) Funds from the European Commission, “A way of making Europe”. This work was partially financed by the Madrid Community grant B2017/BMD3727 and the IiSGM Intramural grant PI-MP-2018. This work was partially funded by a grant from “Fundación Familia Alonso” (FFA-FIBHGM-2019). S.G-M. was supported by the Youth Employment Program, co-financed by the Madrid community and FEDER Founds (PEJ-2020-AI/BMD-17954), and by the ACT4COVID consortium (CellNex funding). The funders had no role in study design, data collection and analysis, decision to publish, or manuscript preparation.S

    Generation of Human Breg-Like Phenotype with Regulatory Function In Vitro with Bacteria-Derived Oligodeoxynucleotides

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    Regulatory B cells (Bregs) participate in auto-tolerance maintenance and immune homeostasis. Despite their impact on many diseases and due to the difficulty to define them, knowledge about their origin and their physiological inducers is still unclear. The incomplete understanding about the generation of Bregs and their limited numbers in periphery make it difficult to develop Breg-based therapy. Therefore, identifying factors that promote their development would allow their ex-vivo production in order to create new immunotherapy. This project aims to test the capacity of several cytokines (Interleukin 1-beta (IL-1β), Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF), and Cluster of differentiation 40 ligand (CD40L)) and bacteria-derived oligodeoxynucleotides (CpG-ODN), alone or in combination, to generate B cells with regulatory phenotype and function. We have demonstrated that the Breg-associated phenotypes were heterogeneous between one and other stimulation conditions. However, the expression of other markers related to Bregs such as IL-10, CD80, CD86, CD71, Programmed cell death-1 (PD-1), and Programmed death-ligand 1 (PD-L1) was increased when cells were stimulated with CpG alone or in combination. Moreover, stimulated B cells presented a suppressive function on autologous activated peripheral blood mononuclear cells (PBMC) proliferation. Therefore, this work is the first step to demonstrate the feasibility to induce functional Breg-like cells in vitro and will then facilitate the way to produce Breg-like cells as a potential future cellular therapy

    CD72/CD100 and PD-1/PD-L1 markers are increased on T and B cells in HIV-1+ viremic individuals, and CD72/CD100 axis is correlated with T-cell exhaustion.

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    In our work, we analyzed the role of the CD100/CD72 and PD-1/PD-L1 axes in immune response dysfunction in human immunodeficiency virus (HIV)-1 infection in which high expressions of PD-1 and PD-L1 were associated with an immunosuppressive state via limitation of the HIV-1-specific T-cell responses. CD100 was demonstrated to play a relevant role in immune responses in various pathological processes and may be responsible for immune dysregulation during HIV-1 infection. We investigated the function of CD72/CD100, and PD-1/PDL-1 axes on T and B cells in HIV-infected individuals and in healthy individuals. We analyzed the frequencies and fluorescence intensities of these four markers on CD4+, CD8+ T and B cells. Marker expressions were increased during active HIV-1 infection. CD100 frequency on T cells was positively associated with the expression of PD-1 and PD-L1 on T cells from HIV-infected treatment-naïve individuals. In addition, the frequency of CD72-expressing T cells was associated with interferon gamma (IFN-γ) production in HIV-infected treatment-naïve individuals. Our data suggest that the CD72/CD100 and PD-1/PD-L1 axes may jointly participate in dysregulation of immunity during HIV-1 infection and could partially explain the immune systems' hyper-activation and exhaustion

    Ectopic FOXP3 Expression in Combination with TGF-β1 and IL-2 Stimulation Generates Limited Suppressive Function in Human Primary Activated Thymocytes Ex Vivo

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    Regulatory T cells (Tregs), which are characterized by the expression of the transcription factor forkhead box P3 (FOXP3), are the main immune cells that induce tolerance and are regulators of immune homeostasis. Natural Treg cells (nTregs), described as CD4+CD25+FOXP3+, are generated in the thymus via activation and cytokine signaling. Transforming growth factor beta type 1 (TGF-β1) is pivotal to the generation of the nTreg lineage, its maintenance in the thymus, and to generating induced Treg cells (iTregs) in the periphery or in vitro arising from conventional T cells (Tconvs). Here, we tested whether TGF-β1 treatment, associated with interleukin-2 (IL-2) and CD3/CD28 stimulation, could generate functional Treg-like cells from human thymocytes in vitro, as it does from Tconvs. Additionally, we genetically manipulated the cells for ectopic FOXP3 expression, along with the TGF-β1 treatment. We demonstrated that TGF-β1 and ectopic FOXP3, combined with IL-2 and through CD3/CD28 activation, transformed human thymocytes into cells that expressed high levels of Treg-associated markers. However, these cells also presented a lack of homogeneous suppressive function and an unstable proinflammatory cytokine profile. Therefore, thymocyte-derived cells, activated with the same stimuli as Tconvs, were not an appropriate alternative for inducing cells with a Treg-like phenotype and function

    VIII Semana de la Facultad de Educación : Desafíos de las pedagogías, las prácticas y las perspectivas investigativas en el siglo XXI.

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    Estas memorias de la viii Semana de la Educación Desafíos de las pedagogías, las prácticas y las perspectivas investigativas en el siglo XXI, publicadas por la editorial de la Corporación Universitaria Minuto de Dios (uniminuto), contienen las ponencias, los talleres y los foros sobre las tendencias actuales de la pedagogía, las prácticas y la investigación que desarrollan los maestros y estudiantes de licenciaturas en las instituciones educativas a nivel preescolar, básica, media y superior. Son ponencias con carácter innovador e incluyente, que responden a los retos actuales de la sociedad y que conducen a la mejora de las condiciones de formación de los ciudadanos que requiere el país, dadas las particularidades de pluralismo propias de nuestras regiones. Durante el encuentro, también se compartieron experiencias artísticas, culturales y deportivas

    VIII Semana de la Facultad de Educación : Desafíos de las pedagogías, las prácticas y las perspectivas investigativas en el siglo XXI.

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    Estas memorias de la viii Semana de la Educación Desafíos de las pedagogías, las prácticas y las perspectivas investigativas en el siglo XXI, publicadas por la editorial de la Corporación Universitaria Minuto de Dios (uniminuto), contienen las ponencias, los talleres y los foros sobre las tendencias actuales de la pedagogía, las prácticas y la investigación que desarrollan los maestros y estudiantes de licenciaturas en las instituciones educativas a nivel preescolar, básica, media y superior. Son ponencias con carácter innovador e incluyente, que responden a los retos actuales de la sociedad y que conducen a la mejora de las condiciones de formación de los ciudadanos que requiere el país, dadas las particularidades de pluralismo propias de nuestras regiones. Durante el encuentro, también se compartieron experiencias artísticas, culturales y deportivas

    The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

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    International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

    The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

    No full text
    International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population
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