Global Assessment of Dengue Virus-Specific CD4+ T Cell Responses in Dengue-Endemic Areas

Grifoni, Alba; Angelo, Michael A.; López, Benjamín; O’Rourke, Patrick; Sidney, John; Cerpas, Cristhiam; Balmaseda, Ángel; Silveira, Cássia G. T.; Maestri, Alvino; Costa, Priscilla R.; Durbin, Anna P.; Diehl, Sean A.; Phillips, Elizabeth; Mallal, S.; Silva, Aruna Dharshan De; Nchinda, Godwin; Nkenfou, Céline Nguefeu; Collins, Matthew H.; Silva, Aravinda M. de; Lim, Mei Qiu; MacAry, Paul A.; Tatullo, Filippo; Solomon, Tom; Satchidanandam, Vijaya; Desai, Anita; Ravi, V; Coloma, Joséfina; Turtle, Lance; Rivino, Laura; Kallas, Esper G.; Peters, Bjoern; Harris, Eva; Sette, Alessandro; Weiskopf, Daniela

doi:10.3389/fimmu.2017.01309

Cited by 71 publications

(89 citation statements)

References 49 publications

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“…However, the source of such massive production of cytokine remains elusive. On the other hand, the majority of the data regarding the physiology of T‐cells in dengue infection suggest a protective role, 5,7,30,31,49–52 but the innate source of this cytokinemia has been poorly investigated. Some data suggest that mast cells 53–55 and macrophages, 56,57 for example, may contribute to early cytokine production and also to severe dengue presentation.…”

Section: Discussionmentioning

confidence: 99%

T‐cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection

et al. 2020

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Multifunctional interleukin 10 (IL10) + Th1 cells have been implicated in favorable evolution of many infectious diseases, promoting an efficacious immune response while limiting immunopathology. Here, we investigated the presence of multifunctional CD4 + and CD8 + T-cells that expressed interferon gamma (IFNc), IL10 and tumor necrosis factor (TNF), or its combinations during dengue infection. Peripheral blood mononuclear cells (PBMCs) from outpatients with dengue (mild dengue forms) and hospitalized patients (or patients with dengue with warning signs and severe dengue) were cultured in the presence of envelope (ENV) or NS3 peptide libraries of DENV during critical (hospitalization period) and convalescence phases. The production of IFNc, IL10 and TNF by CD4 + and CD8 + T-cells was assessed by flow cytometry. Our data show that patients with mild dengue, when compared with patients with dengue with warning signs and severe dengue, presented higher frequencies of multifunctional T-cells like NS3-specific IFNc/IL10-producing CD4 + Tcells in critical phase and NS3-and ENV-specific CD8 + T-cells producing IFNc/IL10. In addition, NS3-specific CD8 + T-cells producing high levels of IFNc/TNF and IFNc/TNF/IL10 were also observed in the mild dengue group. We observed that multifunctional T-cells produced higher levels of cytokines as measured by intracellular content when compared with single producer T-cells. Importantly, multifunctional CD4 + and CD8 + T-cells producing IFNc, TNF and IL10 simultaneously displayed positive correlation with platelet levels, suggesting a protective role of this population. The presence of IL10 + Th1 and IL10 + Tc1 multifunctional cells was associated with mild dengue presentation, suggesting that these cells play a role in clinical evolution of dengue infection.

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Section: Discussionmentioning

confidence: 99%

T‐cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection

et al. 2020

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“…In previous experiments, we showed that pools based on similar peptide numbers can be generated by sequential lyophilization (Carrasco Pro et al, 2015). These peptide pools (or megapools) incorporate predicted or experimentally validated epitopes and allow measurement of magnitude and characterization of the phenotype of human T cell responses in infectious disease indications such as Bordetella pertussis, Mycobacteria tuberculosis, Dengue, and Zika viruses (Carrasco Pro et al, 2015;da Silva Antunes et al, 2018;Grifoni et al, 2017Grifoni et al, , 2018. The SARS-CoV-2 CD4 megapool covers all 10 predicted proteins, with the number of potential epitopes proportional to the size of each protein (Table S4).…”

Section: Prediction Of Sars-cov-2 T Cell Epitopesmentioning

confidence: 99%

A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2

Grifoni

Sidney

Zhang

et al. 2020

Cell Host & Microbe

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Graphical Abstract Highlights d Ten experimentally defined regions within SARS-CoV have high homology with SARS-CoV-2 d Parallel bioinformatics predicted potential B and T cell epitopes for SARS-CoV-2 d Independent approaches identified the same immunodominant regions d The conserved immune regions have implications for vaccine design against multiple CoVs SUMMARYEffective countermeasures against the recent emergence and rapid expansion of the 2019 novel coronavirus (SARS-CoV-2) require the development of data and tools to understand and monitor its spread and immune responses to it. However, little information is available about the targets of immune responses to SARS-CoV-2. We used the Immune Epitope Database and Analysis Resource (IEDB) to catalog available data related to other coronaviruses. This includes SARS-CoV, which has high sequence similarity to SARS-CoV-2 and is the best-characterized coronavirus in terms of epitope responses. We identified multiple specific regions in SARS-CoV-2 that have high homology to the SARS-CoV virus. Parallel bioinformatic predictions identified a priori potential B and T cell epitopes for SARS-CoV-2. The independent identification of the same regions using two approaches reflects the high probability that these regions are promising targets for immune recognition of SARS-CoV-2. These predictions can facilitate effective vaccine design against this virus of high priority.

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“…74 The immunodominant epitopes recognized by CD4 + and CD8 + T cells have been mapped, with CD8 + T cells preferentially targeting NS proteins, such as NS3, NS4b and NS5; and CD4 + T cell responses toward structural proteins and NS1. [91][92][93] Both CD4 + and CD8 + T cell responses have been suggested to mediate protection in animal models or DENV-infected patients (see reviews 65,74,94,95 ). Like B cell immunity, cellular immune responses against DENV can be also cross-reactive against multiple DENV serotypes due to the similarity of genomic sequences.…”

Section: (Un) Balanced T Cell Immunity Of Latv Dengue Vaccinementioning

confidence: 99%

Does structurally-mature dengue virion matter in vaccine preparation in post-Dengvaxia era?

Galula

Salem

Chang

et al. 2019

Human Vaccines & Immunotherapeutics

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The unexpectedly low vaccine efficacy of Dengvaxia®, developed by Sanofi Pasteur, and a higher risk of severe diseases after vaccination among dengue-naive children or children younger than 6 years old, have cast skepticism about the safety of dengue vaccination resulting in the suspension of school-based immunization programs in the Philippines. The absence of immune correlates of protection from dengue virus (DENV) infection hampers the development of other potential DENV vaccines. While tetravalent live-attenuated tetravalent vaccines (LATVs), which mimic natural infection by inducing both cellular and humoral immune responses, are still currently favored, developing a vaccine that provides a balanced immunity to all four DENV serotypes remains a challenge. With the recently advanced understanding of virion structure and B cell immune responses from naturally infected DENV patients, two points of view in developing a next-generation dengue vaccine emerged: one is to induce potent, type-specific neutralizing antibodies (NtAbs) recognizing quaternary structure-dependent epitopes by having four components of vaccine strains replicate equivalently; the other is to induce protective and broadly NtAbs against the four serotypes of DENV with a universal vaccine. This article reviews the studies related to these issues and the current knowledge gap that needs to be filled in.

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Global Assessment of Dengue Virus-Specific CD4+ T Cell Responses in Dengue-Endemic Areas

Cited by 71 publications

References 49 publications

T‐cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection

T‐cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection

A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2

Does structurally-mature dengue virion matter in vaccine preparation in post-Dengvaxia era?

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