805 results on '"Weiskopf, Daniela"'
Search Results
2. Identifying the strains of dengue circulating in the western province of Sri Lanka during 2019-2022.
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Abeygoonawardena, Harshi, Dassanayake, Kanchana, Kariyawasam, Jayani, Chathuranga, Teshan, Sundralingam, Tharmini, Gunasekara, Hansani, Wevita, Sathyani, Premawansa, Gayani, Premawansa, Sunil, Wijewickrama, Ananda, Wijesinghe, Namal, Navaratne, Varuna, Weiskopf, Daniela, Sette, Alessandro, Punchihewa, Chandanamali, and De Silva, Aruna
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A study conducted from July 2019 to May 2022 at several hospitals in the Western Province, Sri Lanka, focused on dengue virus strains during the COVID-19 pandemic. Among 417 febrile patients, 47% were PCR-positive for dengue. Serotyping revealed DENV-1 (12.8%), DENV-2 (46.4%), DENV-3 (37.2%), and DENV-4 (3.6%). Sequencing identified two genotypically distinct variants of DENV-3 and two genotypically distinct variants of DENV-1, while DENV-2 showed a single genotype cluster. Notably, the study found concurrent circulation of two DENV-3 and two DENV-1 genotypes, along with DENV-2, during the pandemic in the area. This data suggests the presence of multiple dengue strains, including several DENV-1 and DENV-3 variants, without major epidemic outbreaks reported in the Western Province. Continuous monitoring and research are essential to understand the dynamics of these dengue strains in the context of the COVID-19 pandemic.
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- 2024
3. SARS-CoV-2 vaccination enhances the effector qualities of spike-specific T cells induced by COVID-19.
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Cai, Curtis, Gao, Yu, Adamo, Sarah, Rivera-Ballesteros, Olga, Hansson, Lotta, Österborg, Anders, Bergman, Peter, Sandberg, Johan, Ljunggren, Hans-Gustaf, Björkström, Niklas, Strålin, Kristoffer, Llewellyn-Lacey, Sian, Price, David, Qin, Chuan, Grifoni, Alba, Wherry, E, Sette, Alessandro, Aleman, Soo, Buggert, Marcus, and Weiskopf, Daniela
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Humans ,CD8-Positive T-Lymphocytes ,COVID-19 ,SARS-CoV-2 ,COVID-19 Vaccines ,Vaccination - Abstract
T cells are critical for immune protection against severe COVID-19, but it has remained unclear whether repeated exposure to SARS-CoV-2 antigens delivered in the context of vaccination fuels T cell exhaustion or reshapes T cell functionality. Here, we sampled convalescent donors with a history of mild or severe COVID-19 before and after SARS-CoV-2 vaccination to profile the functional spectrum of hybrid T cell immunity. Using combined single-cell technologies and high-dimensional flow cytometry, we found that the frequencies and functional capabilities of spike-specific CD4+ and CD8+ T cells in previously infected individuals were enhanced by vaccination, despite concomitant increases in the expression of inhibitory receptors such as PD-1 and TIM3. In contrast, CD4+ and CD8+ T cells targeting non-spike proteins remained functionally static and waned over time, and only minimal effects were observed in healthy vaccinated donors experiencing breakthrough infections with SARS-CoV-2. Moreover, hybrid immunity was characterized by elevated expression of IFN-γ, which was linked with clonotype specificity in the CD8+ T cell lineage. Collectively, these findings identify a molecular hallmark of hybrid immunity and suggest that vaccination after infection is associated with cumulative immunological benefits over time, potentially conferring enhanced protection against subsequent episodes of COVID-19.
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- 2023
4. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination.
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Asashima, Hiromitsu, Kim, Dongjoo, Wang, Kaicheng, Lele, Nikhil, Buitrago-Pocasangre, Nicholas, Lutz, Rachel, Cruz, Isabella, Raddassi, Khadir, Ruff, William, Racke, Michael, Wilson, JoDell, Givens, Tara, Grifoni, Alba, Sette, Alessandro, Kleinstein, Steven, Montgomery, Ruth, Shaw, Albert, Li, Fangyong, Fan, Rong, Hafler, David, Tomayko, Mary, Longbrake, Erin, and Weiskopf, Daniela
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Autoimmune diseases ,Autoimmunity ,COVID-19 ,Multiple sclerosis ,Humans ,Aged ,Antibody Formation ,SARS-CoV-2 ,BNT162 Vaccine ,COVID-19 ,Vaccination ,Antibodies ,Monoclonal ,Antilymphocyte Serum ,RNA ,Messenger - Abstract
BACKGROUNDWhile B cell depletion is associated with attenuated antibody responses to SARS-CoV-2 mRNA vaccination, responses vary among individuals. Thus, elucidating the factors that affect immune responses after repeated vaccination is an important clinical need.METHODSWe evaluated the quality and magnitude of the T cell, B cell, antibody, and cytokine responses to a third dose of BNT162b2 or mRNA-1273 mRNA vaccine in patients with B cell depletion.RESULTSIn contrast with control individuals (n = 10), most patients on anti-CD20 therapy (n = 48) did not demonstrate an increase in spike-specific B cells or antibodies after a third dose of vaccine. A third vaccine elicited significantly increased frequencies of spike-specific non-naive T cells. A small subset of B cell-depleted individuals effectively produced spike-specific antibodies, and logistic regression models identified time since last anti-CD20 treatment and lower cumulative exposure to anti-CD20 mAbs as predictors of those having a serologic response. B cell-depleted patients who mounted an antibody response to 3 vaccine doses had persistent humoral immunity 6 months later.CONCLUSIONThese results demonstrate that serial vaccination strategies can be effective for a subset of B cell-depleted patients.FUNDINGThe NIH (R25 NS079193, P01 AI073748, U24 AI11867, R01 AI22220, UM 1HG009390, P01 AI039671, P50 CA121974, R01 CA227473, U01CA260507, 75N93019C00065, K24 AG042489), NIH HIPC Consortium (U19 AI089992), the National Multiple Sclerosis Society (CA 1061-A-18, RG-1802-30153), the Nancy Taylor Foundation for Chronic Diseases, Erase MS, and the Claude D. Pepper Older Americans Independence Center at Yale (P30 AG21342).
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- 2023
5. SARS-CoV-2 Omicron (B.1.1.529) shows minimal neurotropism in a double-humanized mouse model
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Alves, Rubens Prince Dos Santos, Wang, Ying-Ting, Mikulski, Zbigniew, McArdle, Sara, Shafee, Norazizah, Valentine, Kristen M, Miller, Robyn, Verma, Shailendra Kumar, Batiz, Fernanda Ana Sosa, Maule, Erin, Nguyen, Michael N, Timis, Julia, Mann, Colin, Zandonatti, Michelle, Alarcon, Suzie, Rowe, Jenny, Kronenberg, Mitchell, Weiskopf, Daniela, Sette, Alessandro, Hastie, Kathryn, Saphire, Erica Ollmann, Festin, Stephen, Kim, Kenneth, and Shresta, Sujan
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Biomedical and Clinical Sciences ,Immunology ,Emerging Infectious Diseases ,Lung ,Infectious Diseases ,Coronaviruses ,Biodefense ,2.1 Biological and endogenous factors ,Aetiology ,Infection ,Good Health and Well Being ,Animals ,Humans ,Mice ,SARS-CoV-2 ,COVID-19 ,Brain ,Antiviral Agents ,Disease Models ,Animal ,Omicron ,Neurotropism ,Mouse model ,Human ACE2 ,Human CD34 immune cells ,T cell ,NCG ,Microbiology ,Medical Microbiology ,Pharmacology and Pharmaceutical Sciences ,Virology ,Medical microbiology ,Pharmacology and pharmaceutical sciences - Abstract
Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initially infects the respiratory tract, it also directly or indirectly affects other organs, including the brain. However, little is known about the relative neurotropism of SARS-CoV-2 variants of concern (VOCs), including Omicron (B.1.1.529), which emerged in November 2021 and has remained the dominant pathogenic lineage since then. To address this gap, we examined the relative ability of Omicron, Beta (B.1.351), and Delta (B.1.617.2) to infect the brain in the context of a functional human immune system by using human angiotensin-converting enzyme 2 (hACE2) knock-in triple-immunodeficient NGC mice with or without reconstitution with human CD34+ stem cells. Intranasal inoculation of huCD34+-hACE2-NCG mice with Beta and Delta resulted in productive infection of the nasal cavity, lungs, and brain on day 3 post-infection, but Omicron was surprisingly unique in its failure to infect either the nasal tissue or brain. Moreover, the same infection pattern was observed in hACE2-NCG mice, indicating that antiviral immunity was not responsible for the lack of Omicron neurotropism. In independent experiments, we demonstrate that nasal inoculation with Beta or with D614G, an ancestral SARS-CoV-2 with undetectable replication in huCD34+-hACE2-NCG mice, resulted in a robust response by human innate immune cells, T cells, and B cells, confirming that exposure to SARS-CoV-2, even without detectable infection, is sufficient to induce an antiviral immune response. Collectively, these results suggest that modeling of the neurologic and immunologic sequelae of SARS-CoV-2 infection requires careful selection of the appropriate SARS-CoV-2 strain in the context of a specific mouse model.
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- 2023
6. Unaltered T cell responses to common antigens in individuals with Parkinson's disease
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Williams, Gregory P, Muskat, Kaylin, Frazier, April, Xu, Yaqian, Mateus, José, Grifoni, Alba, da Silva Antunes, Ricardo, Weiskopf, Daniela, Amara, Amy W, Standaert, David G, Goldman, Jennifer G, Litvan, Irene, Alcalay, Roy N, Sulzer, David, Lindestam Arlehamn, Cecilia S, and Sette, Alessandro
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Biotechnology ,Emerging Infectious Diseases ,Prevention ,Neurosciences ,Immunization ,Neurodegenerative ,Infectious Diseases ,Parkinson's Disease ,Brain Disorders ,Vaccine Related ,Clinical Research ,Aging ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,Inflammatory and immune system ,Infection ,Humans ,T-Lymphocytes ,Parkinson Disease ,Leukocytes ,Mononuclear ,Cytokines ,Vaccines ,Parkinson 's disease ,T cells ,Inflammation ,Neuroimmunology ,Immune system ,Viral immunity ,Bacterial immunity ,Neurodegeneration ,Parkinson's disease ,Clinical Sciences ,Psychology ,Clinical sciences ,Biological psychology - Abstract
Background and objectivesParkinson's disease (PD) is associated with a heightened inflammatory state, including activated T cells. However, it is unclear whether these PD T cell responses are antigen specific or more indicative of generalized hyperresponsiveness. Our objective was to measure and compare antigen-specific T cell responses directed towards antigens derived from commonly encountered human pathogens/vaccines in patients with PD and age-matched healthy controls (HC).MethodsPeripheral blood mononuclear cells (PBMCs) from 20 PD patients and 19 age-matched HCs were screened. Antigen specific T cell responses were measured by flow cytometry using a combination of the activation induced marker (AIM) assay and intracellular cytokine staining.ResultsHere we show that both PD patients and HCs show similar T cell activation levels to several antigens derived from commonly encountered human pathogens/vaccines in the general population. Similarly, we also observed no difference between HC and PD in the levels of CD4 and CD8 T cell derived cytokines produced in response to any of the common antigens tested. These antigens encompassed both viral (coronavirus, rhinovirus, respiratory syncytial virus, influenza, cytomegalovirus) and bacterial (pertussis, tetanus) targets.ConclusionsThese results suggest the T cell dysfunction observed in PD may not extend itself to abnormal responses to commonly encountered or vaccine-target antigens. Our study supports the notion that the targets of inflammatory T cell responses in PD may be more directed towards autoantigens like α-synuclein (α-syn) rather than common foreign antigens.
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- 2023
7. Bamlanivimab therapy for acute COVID-19 does not blunt SARS-CoV-2-specific memory T cell responses
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Ramirez, Sydney I, Grifoni, Alba, Weiskopf, Daniela, Parikh, Urvi M, Heaps, Amy, Faraji, Farhoud, Sieg, Scott F, Ritz, Justin, Moser, Carlee, Eron, Joseph J, Currier, Judith S, Klekotka, Paul, Sette, Alessandro, Wohl, David A, Daar, Eric S, Hughes, Michael D, Chew, Kara W, Smith, Davey M, Crotty, Shane, and Team, for the Accelerating COVID-19 Therapeutic Interventions and Vaccines–2 A5401 Study
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Biomedical and Clinical Sciences ,Immunology ,Vaccine Related ,Infectious Diseases ,Clinical Research ,Biodefense ,Emerging Infectious Diseases ,Lung ,Pneumonia ,Pneumonia & Influenza ,Prevention ,Inflammatory and immune system ,Good Health and Well Being ,Humans ,SARS-CoV-2 ,COVID-19 ,Memory T Cells ,Antibodies ,Monoclonal ,Humanized ,Antibodies ,Viral ,Accelerating COVID-19 Therapeutic Interventions and Vaccines–2/A5401 (ACTIV-2/A5401) Study Team ,Adaptive immunity ,Biomedical and clinical sciences ,Health sciences - Abstract
Despite the widespread use of SARS-CoV-2-specific monoclonal antibody (mAb) therapy for the treatment of acute COVID-19, the impact of this therapy on the development of SARS-CoV-2-specific T cell responses has been unknown, resulting in uncertainty as to whether anti-SARS-CoV-2 mAb administration may result in failure to generate immune memory. Alternatively, it has been suggested that SARS-CoV-2-specific mAb may enhance adaptive immunity to SARS-CoV-2 via a "vaccinal effect." Bamlanivimab (Eli Lilly and Company) is a recombinant human IgG1 that was granted FDA emergency use authorization for the treatment of mild to moderate COVID-19 in those at high risk for progression to severe disease. Here, we compared SARS-CoV-2-specific CD4+ and CD8+ T cell responses of 95 individuals from the ACTIV-2/A5401 clinical trial 28 days after treatment with bamlanivimab versus placebo. SARS-CoV-2-specific T cell responses were evaluated using activation-induced marker assays in conjunction with intracellular cytokine staining. We demonstrate that most individuals with acute COVID-19 developed SARS-CoV-2-specific T cell responses. Overall, our findings suggest that the quantity and quality of SARS-CoV-2-specific T cell memory were not diminished in individuals who received bamlanivimab for acute COVID-19. Receipt of bamlanivimab during acute COVID-19 neither diminished nor enhanced SARS-CoV-2-specific cellular immunity.
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- 2022
8. Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques
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He, Wan-Ting, Yuan, Meng, Callaghan, Sean, Musharrafieh, Rami, Song, Ge, Silva, Murillo, Beutler, Nathan, Lee, Wen-Hsin, Yong, Peter, Torres, Jonathan L, Melo, Mariane, Zhou, Panpan, Zhao, Fangzhu, Zhu, Xueyong, Peng, Linghang, Huang, Deli, Anzanello, Fabio, Ricketts, James, Parren, Mara, Garcia, Elijah, Ferguson, Melissa, Rinaldi, William, Rawlings, Stephen A, Nemazee, David, Smith, Davey M, Briney, Bryan, Safonova, Yana, Rogers, Thomas F, Dan, Jennifer M, Zhang, Zeli, Weiskopf, Daniela, Sette, Alessandro, Crotty, Shane, Irvine, Darrell J, Ward, Andrew B, Wilson, Ian A, Burton, Dennis R, and Andrabi, Raiees
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Vaccine Related ,Pneumonia & Influenza ,Emerging Infectious Diseases ,Biotechnology ,Biodefense ,Prevention ,Immunization ,Vaccine Related (AIDS) ,Pneumonia ,Lung ,Infectious Diseases ,Infection ,Good Health and Well Being ,Animals ,Antibodies ,Neutralizing ,Antibodies ,Viral ,Broadly Neutralizing Antibodies ,COVID-19 ,Epitopes ,Humans ,Macaca mulatta ,SARS-CoV-2 ,Spike Glycoprotein ,Coronavirus ,Biological Sciences ,Medical and Health Sciences ,Medical biotechnology ,Biomedical engineering - Abstract
To prepare for future coronavirus (CoV) pandemics, it is desirable to generate vaccines capable of eliciting broadly neutralizing antibody responses to CoVs. Here, we show that immunization of macaques with SARS-CoV-2 spike (S) protein with a two-shot protocol generated potent serum receptor binding domain cross-neutralizing antibody responses to both SARS-CoV-2 and SARS-CoV-1. Furthermore, responses were equally effective against most SARS-CoV-2 variants of concern (VOCs) and some were highly effective against Omicron. This result contrasts with human infection or many two-shot vaccination protocols where responses were typically more SARS-CoV-2 specific and where VOCs were less well neutralized. Structural studies showed that cloned macaque neutralizing antibodies, particularly using a given heavy chain germline gene, recognized a relatively conserved region proximal to the angiotensin converting enzyme 2 receptor binding site (RBS), whereas many frequently elicited human neutralizing antibodies targeted more variable epitopes overlapping the RBS. B cell repertoire differences between humans and macaques appeared to influence the vaccine response. The macaque neutralizing antibodies identified a pan-SARS-related virus epitope region less well targeted by human antibodies that could be exploited in rational vaccine design.
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- 2022
9. Cytokine profile of anti-spike CD4+T cells predicts humoral and CD8+T cell responses after anti-SARS-CoV-2 mRNA vaccination
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Benhamouda, Nadine, Besbes, Anissa, Bauer, Rebecca, Mabrouk, Nesrine, Gadouas, Gauthier, Desaint, Corinne, Chevrier, Lucie, Lefebvre, Maeva, Radenne, Anne, Roelens, Marie, Parfait, Béatrice, Weiskopf, Daniela, Sette, Alessandro, Gruel, Nadège, Courbebaisse, Marie, Appay, Victor, Paul, Stephane, Gorochov, Guy, Ropers, Jacques, Lebbah, Said, Lelievre, Jean-Daniel, Johannes, Ludger, Ulmer, Jonathan, Lebeaux, David, Friedlander, Gerard, De Lamballerie, Xavier, Ravel, Patrice, Kieny, Marie Paule, Batteux, Fréderic, Durier, Christine, Launay, Odile, and Tartour, Eric
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- 2024
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10. Prior vaccination promotes early activation of memory T cells and enhances immune responses during SARS-CoV-2 breakthrough infection
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Painter, Mark M., Johnston, Timothy S., Lundgreen, Kendall A., Santos, Jefferson J. S., Qin, Juliana S., Goel, Rishi R., Apostolidis, Sokratis A., Mathew, Divij, Fulmer, Bria, Williams, Justine C., McKeague, Michelle L., Pattekar, Ajinkya, Goode, Ahmad, Nasta, Sean, Baxter, Amy E., Giles, Josephine R., Skelly, Ashwin N., Felley, Laura E., McLaughlin, Maura, Weaver, Joellen, Kuthuru, Oliva, Dougherty, Jeanette, Adamski, Sharon, Long, Sherea, Kee, Macy, Clendenin, Cynthia, da Silva Antunes, Ricardo, Grifoni, Alba, Weiskopf, Daniela, Sette, Alessandro, Huang, Alexander C., Rader, Daniel J., Hensley, Scott E., Bates, Paul, Greenplate, Allison R., and Wherry, E. John
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- 2023
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11. SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents
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Garcia-Valtanen, Pablo, Hope, Christopher M, Masavuli, Makutiro G, Yeow, Arthur Eng Lip, Balachandran, Harikrishnan, Mekonnen, Zelalem A, Al-Delfi, Zahraa, Abayasingam, Arunasingam, Agapiou, David, Stella, Alberto Ospina, Aggarwal, Anupriya, Bouras, George, Gummow, Jason, Ferguson, Catherine, O’Connor, Stephanie, McCartney, Erin M, Lynn, David J, Maddern, Guy, Gowans, Eric J, Reddi, Benjamin AJ, Shaw, David, Kok-Lim, Chuan, Beard, Michael R, Weiskopf, Daniela, Sette, Alessandro, Turville, Stuart G, Bull, Rowena A, Barry, Simon C, and Grubor-Bauk, Branka
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Infectious Diseases ,Pneumonia & Influenza ,Pneumonia ,Prevention ,Biodefense ,Lung ,Immunization ,Vaccine Related ,Emerging Infectious Diseases ,Infection ,Good Health and Well Being ,Antibodies ,Neutralizing ,Antibodies ,Viral ,COVID-19 ,Humans ,Reinfection ,SARS-CoV-2 ,Spike Glycoprotein ,Coronavirus ,T-Lymphocytes ,T cell immunity ,Variant of Concern ,antibody response ,antigen drift ,memory B cells ,virus neutralization - Abstract
Coronavirus disease 2019 (COVID-19) convalescents living in regions with low vaccination rates rely on post-infection immunity for protection against re-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluate humoral and T cell immunity against five variants of concern (VOCs) in mild-COVID-19 convalescents at 12 months after infection with ancestral virus. In this cohort, ancestral, receptor-binding domain (RBD)-specific antibody and circulating memory B cell levels are conserved in most individuals, and yet serum neutralization against live B.1.1.529 (Omicron) is completely abrogated and significantly reduced for other VOCs. Likewise, ancestral SARS-CoV-2-specific memory T cell frequencies are maintained in >50% of convalescents, but the cytokine response in these cells to mutated spike epitopes corresponding to B.1.1.529 and B.1.351 (Beta) VOCs were impaired. These results indicate that increased antigen variability in VOCs impairs humoral and spike-specific T cell immunity post-infection, strongly suggesting that COVID-19 convalescents are vulnerable and at risk of re-infection with VOCs, thus stressing the importance of vaccination programs.
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- 2022
12. Mission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies
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Figueiredo, Jane C, Hirsch, Fred R, Kushi, Lawrence H, Nembhard, Wendy N, Crawford, James M, Mantis, Nicholas, Finster, Laurel, Merin, Noah M, Merchant, Akil, Reckamp, Karen L, Melmed, Gil Y, Braun, Jonathan, McGovern, Dermot, Parekh, Samir, Corley, Douglas A, Zohoori, Namvar, Amick, Benjamin C, Du, Ruofei, Gregersen, Peter K, Diamond, Betty, Taioli, Emanuela, Sariol, Carlos, Espino, Ana, Weiskopf, Daniela, Gifoni, Alba, Brien, James, Hanege, William, Lipsitch, Marc, Zidar, David A, McAlearney, Ann Scheck, Wajnberg, Ania, LaBaer, Joshua, Lewis, E Yvonne, Binder, Raquel A, Moormann, Ann M, Forconi, Catherine, Forrester, Sarah, Batista, Jennifer, Schieffelin, John, Kim, Dongjoo, Biancon, Giulia, VanOudenhove, Jennifer, Halene, Stephanie, Fan, Rong, Barouch, Dan H, Alter, Galit, Pinninti, Swetha, Boppana, Suresh B, Pati, Sunil K, Latting, Misty, Karaba, Andrew H, Roback, John, Sekaly, Rafick, Neish, Andrew, Brincks, Ahnalee M, Granger, Douglas A, Karger, Amy B, Thyagarajan, Bharat, Thomas, Stefani N, Klein, Sabra L, Cox, Andrea L, Lucas, Todd, Furr-Holden, Debra, Key, Kent, Jones, Nicole, Wrammerr, Jens, Suthar, Mehul, Wong, Serre Yu, Bowman, Natalie M, Simon, Viviana, Richardson, Lynne D, McBride, Russell, Krammer, Florian, Rana, Meenakshi, Kennedy, Joshua, Boehme, Karl, Forrest, Craig, Granger, Steve W, Heaney, Christopher D, Lapinski, Maria Knight, Wallet, Shannon, Baric, Ralph S, Schifanella, Luca, Lopez, Marcos, Fernández, Soledad, Kenah, Eben, Panchal, Ashish R, Britt, William J, Sanz, Iñaki, Dhodapkar, Madhav, Ahmed, Rafi, Bartelt, Luther A, Markmann, Alena J, Lin, Jessica T, Hagan, Robert S, Wolfgang, Matthew C, and Skarbinski, Jacek
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Biomedical and Clinical Sciences ,Clinical Sciences ,Pneumonia & Influenza ,Vaccine Related ,Emerging Infectious Diseases ,Biodefense ,Lung ,Digestive Diseases ,Infectious Diseases ,Clinical Research ,Pneumonia ,Cancer ,Pediatric ,Prevention ,Aetiology ,2.4 Surveillance and distribution ,Good Health and Well Being ,cohort ,COVID-19 ,epidemiology ,SARS-CoV-2 ,serosurveillance ,SeroNet ,Clinical sciences ,Medical microbiology - Abstract
BackgroundGlobal efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the underlying cause of coronavirus disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well as immune responses after vaccination across populations and the social dimensions of prevention and treatment strategies.MethodsIn the United States, the National Cancer Institute in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network (SeroNet) as the nation's largest coordinated effort to study coronavirus disease 2019. The network comprises multidisciplinary researchers bridging gaps and fostering collaborations among immunologists, epidemiologists, virologists, clinicians and clinical laboratories, social and behavioral scientists, policymakers, data scientists, and community members. In total, 49 institutions form the SeroNet consortium to study individuals with cancer, autoimmune disease, inflammatory bowel diseases, cardiovascular diseases, human immunodeficiency virus, transplant recipients, as well as otherwise healthy pregnant women, children, college students, and high-risk occupational workers (including healthcare workers and first responders).ResultsSeveral studies focus on underrepresented populations, including ethnic minorities and rural communities. To support integrative data analyses across SeroNet studies, efforts are underway to define common data elements for standardized serology measurements, cellular and molecular assays, self-reported data, treatment, and clinical outcomes.ConclusionsIn this paper, we discuss the overarching framework for SeroNet epidemiology studies, critical research questions under investigation, and data accessibility for the worldwide scientific community. Lessons learned will help inform preparedness and responsiveness to future emerging diseases.
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- 2022
13. Respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination
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Mitsi, Elena, Diniz, Mariana O., Reiné, Jesús, Collins, Andrea M., Robinson, Ryan E., Hyder-Wright, Angela, Farrar, Madlen, Liatsikos, Konstantinos, Hamilton, Josh, Onyema, Onyia, Urban, Britta C., Solórzano, Carla, Belij-Rammerstorfer, Sandra, Sheehan, Emma, Lambe, Teresa, Draper, Simon J., Weiskopf, Daniela, Sette, Alessandro, Maini, Mala K., and Ferreira, Daniela M.
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- 2023
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14. Metabolic dysregulation impairs lymphocyte function during severe SARS-CoV-2 infection
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Gurshaney, Sanjeev, Morales-Alvarez, Anamaria, Ezhakunnel, Kevin, Manalo, Andrew, Huynh, Thien-Huong, Abe, Jun-Ichi, Le, Nhat-Tu, Weiskopf, Daniela, Sette, Alessandro, Lupu, Daniel S., Gardell, Stephen J., and Nguyen, Hung
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- 2023
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15. Development of a T cell-based immunodiagnostic system to effectively distinguish SARS-CoV-2 infection and COVID-19 vaccination status
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Yu, Esther Dawen, Wang, Eric, Garrigan, Emily, Goodwin, Benjamin, Sutherland, Aaron, Tarke, Alison, Chang, James, Gálvez, Rosa Isela, Mateus, Jose, Ramirez, Sydney I, Rawlings, Stephen A, Smith, Davey M, Filaci, Gilberto, Frazier, April, Weiskopf, Daniela, Dan, Jennifer M, Crotty, Shane, Grifoni, Alba, Sette, Alessandro, and da Silva Antunes, Ricardo
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Vaccine Related ,Immunization ,Biodefense ,Lung ,Infectious Diseases ,Pneumonia & Influenza ,Prevention ,Emerging Infectious Diseases ,3.4 Vaccines ,Prevention of disease and conditions ,and promotion of well-being ,Infection ,Good Health and Well Being ,Antibodies ,Viral ,COVID-19 ,COVID-19 Vaccines ,Epitopes ,T-Lymphocyte ,Humans ,SARS-CoV-2 ,Spike Glycoprotein ,Coronavirus ,Vaccination ,T cells ,breakthrough infection ,epitope ,immunodiagnostic tool ,vaccination ,viruses ,Microbiology ,Medical Microbiology ,Immunology - Abstract
Both SARS-CoV-2 infections and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of 2 pools of experimentally defined SARS-CoV-2 T cell epitopes that, in combination with spike, were used to discriminate 4 groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status. The overall T cell-based classification accuracy was 89.2% and 88.5% in the experimental and validation cohorts. This scheme was applicable to different mRNA vaccines and different lengths of time post infection/post vaccination and yielded increased accuracy when compared to serological readouts. T cell responses from breakthrough infections were also studied and effectively segregated from vaccine responses, with a combined performance of 86.6% across all 239 subjects from the 5 groups. We anticipate that a T cell-based immunodiagnostic scheme to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccinations and for establishing SARS-CoV-2 correlates of protection.
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- 2022
16. A Population of CD4+CD8+ Double-Positive T Cells Associated with Risk of Plasma Leakage in Dengue Viral Infection.
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Yu, Esther Dawen, Wang, Hao, da Silva Antunes, Ricardo, Tian, Yuan, Tippalagama, Rashmi, Alahakoon, Shakila U, Premawansa, Gayani, Wijewickrama, Ananda, Premawansa, Sunil, De Silva, Aruna Dharshan, Frazier, April, Grifoni, Alba, Sette, Alessandro, and Weiskopf, Daniela
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T-Lymphocyte Subsets ,CD4-Positive T-Lymphocytes ,CD8-Positive T-Lymphocytes ,Plasma ,Humans ,Dengue ,Lymphocyte Count ,Adult ,Female ,Male ,Young Adult ,Transcriptome ,Severe Dengue ,CD4+ ,CD8+ ,T cells ,dengue ,double positive ,infectious diseases ,plasma leakage ,transcriptomic analysis ,Infectious Diseases ,Prevention ,Emerging Infectious Diseases ,Rare Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Infection ,Good Health and Well Being ,CD4(+) ,CD8(+) ,Microbiology - Abstract
According to the WHO 2009 classification, dengue with warning signs is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which can be a serious complication associated with higher morbidity and mortality. We report that the frequency of CD4+CD8+ double-positive (DP) T cells is significantly increased in patients at risk of developing plasma leakage. Transcriptomic analysis demonstrated that CD4+CD8+ DP cells were distinct from CD4+ Single Positive (SP) T cells but co-clustered with CD8+ SP cells, indicating a largely similar transcriptional profile. Twenty significant differentially expressed (DE) genes were identified between CD4+CD8+ DP and CD8+ SP cells. These genes encode OX40 and CCR4 proteins as well as other molecules associated with cell signaling on the cell surface (NT5E, MXRA8, and PTPRK). While comparing the profile of gene expression in CD4+CD8+ DP cells from patients with and without warning signs of plasma leakage, similar expression profile was observed, implying a role of CD4+CD8+ DP cells in plasma leakage through a quantitative increase rather than functional alteration. This study provided novel insight into the host immune response during the acute febrile phase of DENV infection and the role of CD4+CD8+ DP T cells in the pathogenesis of plasma leakage.
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- 2022
17. Preserved SARS-CoV-2 Vaccine Cell-Mediated Immunogenicity in Patients With Inflammatory Bowel Disease on Immune-Modulating Therapies
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Boland, Brigid S, Goodwin, Benjamin, Zhang, Zeli, Bloom, Nathaniel, Kato, Yu, Neill, Jennifer, Le, Helen, Tysl, Tiffani, Collins, Angelina E, Dulai, Parambir S, Singh, Siddharth, Nguyen, Nghia H, Grifoni, Alba, Sette, Alessandro, Weiskopf, Daniela, Chang, John T, and Dan, Jennifer M
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Emerging Infectious Diseases ,Biodefense ,Inflammatory Bowel Disease ,Pneumonia & Influenza ,Infectious Diseases ,Clinical Research ,Lung ,Immunization ,Vaccine Related ,Digestive Diseases ,Autoimmune Disease ,Prevention ,Crohn's Disease ,Pneumonia ,Prevention of disease and conditions ,and promotion of well-being ,3.4 Vaccines ,Good Health and Well Being ,COVID-19 ,COVID-19 Vaccines ,Chronic Disease ,Humans ,Inflammatory Bowel Diseases ,Infliximab ,SARS-CoV-2 ,Clinical Sciences ,Clinical sciences - Abstract
Immune-modulating medications for inflammatory bowel diseases (IBDs) have been associated with suboptimal vaccine responses. There are conflicting data with SARS-CoV-2 vaccination. We therefore assessed SARS-CoV-2 vaccine immunogenicity at 2 weeks after second mRNA vaccination in 29 patients with IBD compared with 12 normal healthy donors. We observed reduced humoral immunity in patients with IBD on infliximab. However, we observed no difference in humoral and cell-mediated immunity in patients with IBD on infliximab with a thiopurine or vedolizumab compared with normal healthy donors. This is the first study to demonstrate comparable cell-mediated immunity with SARS-CoV-2 vaccination in patients with IBD treated with different immune-modulating medications.
- Published
- 2022
18. Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals.
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Tarke, Alison, Sidney, John, Methot, Nils, Yu, Esther Dawen, Zhang, Yun, Dan, Jennifer M, Goodwin, Benjamin, Rubiro, Paul, Sutherland, Aaron, Wang, Eric, Frazier, April, Ramirez, Sydney I, Rawlings, Stephen A, Smith, Davey M, da Silva Antunes, Ricardo, Peters, Bjoern, Scheuermann, Richard H, Weiskopf, Daniela, Crotty, Shane, Grifoni, Alba, and Sette, Alessandro
- Subjects
CD4 ,CD8 ,COVID-19 ,SARS-CoV-2 ,T cells ,VOCs ,vaccines - Abstract
The emergence of SARS-CoV-2 variants with evidence of antibody escape highlight the importance of addressing whether the total CD4+ and CD8+ T cell recognition is also affected. Here, we compare SARS-CoV-2-specific CD4+ and CD8+ T cells against the B.1.1.7, B.1.351, P.1, and CAL.20C lineages in COVID-19 convalescents and in recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. The total reactivity against SARS-CoV-2 variants is similar in terms of magnitude and frequency of response, with decreases in the 10%-22% range observed in some assay/VOC combinations. A total of 7% and 3% of previously identified CD4+ and CD8+ T cell epitopes, respectively, are affected by mutations in the various VOCs. Thus, the SARS-CoV-2 variants analyzed here do not significantly disrupt the total SARS-CoV-2 T cell reactivity; however, the decreases observed highlight the importance for active monitoring of T cell reactivity in the context of SARS-CoV-2 evolution.
- Published
- 2021
19. Spike protein is a key target for stronger and more persistent T-cell responses—a study of mild and asymptomatic SARS-CoV-2 infection
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Ssali, Ivan, Mugaba, Susan, Watelo, Arthur Kalyebi, Bemanzi, Juliana, Katende, Joseph Ssebwana, Oluka, Gerald Kevin, Ankunda, Violet, Baine, Claire, Kato, Laban, Onyachi, Nathan, Muwanga, Moses, Jjuuko, Mark, Kayiwa, John, Nsereko, Christopher, Auma, Betty Oliver, Weiskopf, Daniela, Sette, Alessandro, Lutalo, Tom, Musenero, Monica, Kaleebu, Pontiano, and Serwanga, Jennifer
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- 2023
- Full Text
- View/download PDF
20. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection
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Dan, Jennifer M, Mateus, Jose, Kato, Yu, Hastie, Kathryn M, Yu, Esther Dawen, Faliti, Caterina E, Grifoni, Alba, Ramirez, Sydney I, Haupt, Sonya, Frazier, April, Nakao, Catherine, Rayaprolu, Vamseedhar, Rawlings, Stephen A, Peters, Bjoern, Krammer, Florian, Simon, Viviana, Saphire, Erica Ollmann, Smith, Davey M, Weiskopf, Daniela, Sette, Alessandro, and Crotty, Shane
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Immunization ,Lung ,Prevention ,Pneumonia ,Pneumonia & Influenza ,Emerging Infectious Diseases ,Vaccine Related ,Infectious Diseases ,Biodefense ,Infection ,Inflammatory and immune system ,Good Health and Well Being ,Adult ,Aged ,Aged ,80 and over ,Antibodies ,Neutralizing ,Antibodies ,Viral ,B-Lymphocytes ,CD4-Positive T-Lymphocytes ,CD8-Positive T-Lymphocytes ,COVID-19 ,Cross-Sectional Studies ,Female ,Humans ,Immunologic Memory ,Longitudinal Studies ,Male ,Middle Aged ,Spike Glycoprotein ,Coronavirus ,United States ,Young Adult ,General Science & Technology - Abstract
Understanding immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics and vaccines and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥6 months after infection. Immunoglobulin G (IgG) to the spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month after symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3 to 5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
- Published
- 2021
21. Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases
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Tarke, Alison, Sidney, John, Kidd, Conner K, Dan, Jennifer M, Ramirez, Sydney I, Yu, Esther Dawen, Mateus, Jose, da Silva Antunes, Ricardo, Moore, Erin, Rubiro, Paul, Methot, Nils, Phillips, Elizabeth, Mallal, Simon, Frazier, April, Rawlings, Stephen A, Greenbaum, Jason A, Peters, Bjoern, Smith, Davey M, Crotty, Shane, Weiskopf, Daniela, Grifoni, Alba, and Sette, Alessandro
- Subjects
Infectious Diseases ,Emerging Infectious Diseases ,Biodefense ,Pneumonia & Influenza ,Vaccine Related ,Immunization ,Prevention ,Lung ,Pneumonia ,2.1 Biological and endogenous factors ,Aetiology ,Infection ,Good Health and Well Being ,CD4+T cells ,CD8+ T cells ,COVID-19 ,HLA ,SARS-CoV-2 ,T cells ,epitopes - Abstract
T cells are involved in control of SARS-CoV-2 infection. To establish the patterns of immunodominance of different SARS-CoV-2 antigens and precisely measure virus-specific CD4+ and CD8+ T cells, we study epitope-specific T cell responses of 99 convalescent coronavirus disease 2019 (COVID-19) cases. The SARS-CoV-2 proteome is probed using 1,925 peptides spanning the entire genome, ensuring an unbiased coverage of human leukocyte antigen (HLA) alleles for class II responses. For HLA class I, we study an additional 5,600 predicted binding epitopes for 28 prominent HLA class I alleles, accounting for wide global coverage. We identify several hundred HLA-restricted SARS-CoV-2-derived epitopes. Distinct patterns of immunodominance are observed, which differ for CD4+ T cells, CD8+ T cells, and antibodies. The class I and class II epitopes are combined into epitope megapools to facilitate identification and quantification of SARS-CoV-2-specific CD4+ and CD8+ T cells.
- Published
- 2021
22. A measles virus-based vaccine induces robust chikungunya virus-specific CD4+ T-cell responses in a phase II clinical trial
- Author
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Schmitz, Katharina S., Comvalius, Anouskha D., Nieuwkoop, Nella J., Geers, Daryl, Weiskopf, Daniela, Ramsauer, Katrin, Sette, Alessandro, Tschismarov, Roland, de Vries, Rory D., and de Swart, Rik L.
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- 2023
- Full Text
- View/download PDF
23. SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques.
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Shaan Lakshmanappa, Yashavanth, Elizaldi, Sonny R, Roh, Jamin W, Schmidt, Brian A, Carroll, Timothy D, Weaver, Kourtney D, Smith, Justin C, Verma, Anil, Deere, Jesse D, Dutra, Joseph, Stone, Mars, Franz, Sergej, Sammak, Rebecca Lee, Olstad, Katherine J, Rachel Reader, J, Ma, Zhong-Min, Nguyen, Nancy K, Watanabe, Jennifer, Usachenko, Jodie, Immareddy, Ramya, Yee, JoAnn L, Weiskopf, Daniela, Sette, Alessandro, Hartigan-O'Connor, Dennis, McSorley, Stephen J, Morrison, John H, Tran, Nam K, Simmons, Graham, Busch, Michael P, Kozlowski, Pamela A, Van Rompay, Koen KA, Miller, Christopher J, and Iyer, Smita S
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Germinal Center ,Th1 Cells ,Cell Line ,Vero Cells ,Animals ,Macaca mulatta ,Humans ,Disease Models ,Animal ,Immunoglobulin G ,Phosphoproteins ,Antibodies ,Viral ,Immunization ,Passive ,Female ,Male ,Immunity ,Humoral ,Spike Glycoprotein ,Coronavirus ,Immunogenicity ,Vaccine ,Chlorocebus aethiops ,COVID-19 ,SARS-CoV-2 ,Coronavirus Nucleocapsid Proteins ,T Follicular Helper Cells ,Disease Models ,Animal ,Antibodies ,Viral ,Immunization ,Passive ,Immunity ,Humoral ,Spike Glycoprotein ,Coronavirus ,Immunogenicity ,Vaccine - Abstract
CD4 T follicular helper (Tfh) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center (GC) response is an important question as we investigate vaccine induced immunity against COVID-19. Here, we report that SARS-CoV-2 infection in rhesus macaques, either infused with convalescent plasma, normal plasma, or receiving no infusion, resulted in transient accumulation of pro-inflammatory monocytes and proliferating Tfh cells with a Th1 profile in peripheral blood. CD4 helper cell responses skewed predominantly toward a Th1 response in blood, lung, and lymph nodes. SARS-CoV-2 Infection induced GC Tfh cells specific for the SARS-CoV-2 spike and nucleocapsid proteins, and a corresponding early appearance of antiviral serum IgG antibodies. Collectively, the data show induction of GC responses in a rhesus model of mild COVID-19.
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- 2021
24. Immunological memory to SARS-CoV-2 assessed for up to eight months after infection
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Dan, Jennifer M, Mateus, Jose, Kato, Yu, Hastie, Kathryn M, Yu, Esther Dawen, Faliti, Caterina E, Grifoni, Alba, Ramirez, Sydney I, Haupt, Sonya, Frazier, April, Nakao, Catherine, Rayaprolu, Vamseedhar, Rawlings, Stephen A, Peters, Bjoern, Krammer, Florian, Simon, Viviana, Saphire, Erica Ollmann, Smith, Davey M, Weiskopf, Daniela, Sette, Alessandro, and Crotty, Shane
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Vaccine Related ,Prevention ,Lung ,Immunization ,Biodefense ,Emerging Infectious Diseases ,Infectious Diseases ,Pneumonia ,Pneumonia & Influenza ,Inflammatory and immune system ,Infection ,Good Health and Well Being - Abstract
Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4 + T cells and CD8 + T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4 + T cell, and CD8 + T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
- Published
- 2020
25. Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases
- Author
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Tarke, Alison, Sidney, John, Kidd, Conner K, Dan, Jennifer M, Ramirez, Sydney I, Yu, Esther Dawen, Mateus, Jose, da Silva Antunes, Ricardo, Moore, Erin, Rubiro, Paul, Methot, Nils, Phillips, Elizabeth, Mallal, Simon, Frazier, April, Rawlings, Stephen A, Greenbaum, Jason A, Peters, Bjoern, Smith, Davey M, Crotty, Shane, Weiskopf, Daniela, Grifoni, Alba, and Sette, Alessandro
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,Genetics ,Vaccine Related ,Prevention ,Biodefense ,Emerging Infectious Diseases ,Lung ,Pneumonia ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being - Abstract
T cells are involved in control of SARS-CoV-2 infection. To establish the patterns of immunodominance of different SARS-CoV-2 antigens, and precisely measure virus-specific CD4 + and CD8 + T cells, we studied epitope-specific T cell responses of approximately 100 convalescent COVID-19 cases. The SARS-CoV-2 proteome was probed using 1,925 peptides spanning the entire genome, ensuring an unbiased coverage of HLA alleles for class II responses. For HLA class I, we studied an additional 5,600 predicted binding epitopes for 28 prominent HLA class I alleles, accounting for wide global coverage. We identified several hundred HLA-restricted SARS-CoV-2-derived epitopes. Distinct patterns of immunodominance were observed, which differed for CD4 + T cells, CD8 + T cells, and antibodies. The class I and class II epitopes were combined into new epitope megapools to facilitate identification and quantification of SARS-CoV-2-specific CD4 + and CD8 + T cells.
- Published
- 2020
26. Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity
- Author
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Moderbacher, Carolyn Rydyznski, Ramirez, Sydney I, Dan, Jennifer M, Grifoni, Alba, Hastie, Kathryn M, Weiskopf, Daniela, Belanger, Simon, Abbott, Robert K, Kim, Christina, Choi, Jinyong, Kato, Yu, Crotty, Eleanor G, Kim, Cheryl, Rawlings, Stephen A, Mateus, Jose, Tse, Long Ping Victor, Frazier, April, Baric, Ralph, Peters, Bjoern, Greenbaum, Jason, Saphire, Erica Ollmann, Smith, Davey M, Sette, Alessandro, and Crotty, Shane
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Emerging Infectious Diseases ,Lung ,Biodefense ,Infectious Diseases ,Vaccine Related ,Immunization ,Pneumonia ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Good Health and Well Being ,Acute Disease ,Adaptive Immunity ,Adult ,Aged ,Aged ,80 and over ,Antibodies ,Neutralizing ,Antibodies ,Viral ,Antigens ,Viral ,Betacoronavirus ,CD4-Positive T-Lymphocytes ,CD8-Positive T-Lymphocytes ,COVID-19 ,Coronavirus Infections ,Cytokines ,Female ,Humans ,Male ,Middle Aged ,Pandemics ,Pneumonia ,Viral ,SARS-CoV-2 ,Severity of Illness Index ,Young Adult ,CD4 ,CD8 ,CXCL10 ,IP-10 ,Spike ,T cells ,adaptive immunity ,antibody ,coronavirus ,epitopes ,neutralizing antibodies ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.
- Published
- 2020
27. Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity.
- Author
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Rydyznski Moderbacher, Carolyn, Ramirez, Sydney I, Dan, Jennifer M, Grifoni, Alba, Hastie, Kathryn M, Weiskopf, Daniela, Belanger, Simon, Abbott, Robert K, Kim, Christina, Choi, Jinyong, Kato, Yu, Crotty, Eleanor G, Kim, Cheryl, Rawlings, Stephen A, Mateus, Jose, Tse, Long Ping Victor, Frazier, April, Baric, Ralph, Peters, Bjoern, Greenbaum, Jason, Ollmann Saphire, Erica, Smith, Davey M, Sette, Alessandro, and Crotty, Shane
- Subjects
CD4-Positive T-Lymphocytes ,CD8-Positive T-Lymphocytes ,Humans ,Pneumonia ,Viral ,Coronavirus Infections ,Acute Disease ,Antibodies ,Viral ,Antigens ,Viral ,Cytokines ,Severity of Illness Index ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Young Adult ,Adaptive Immunity ,Antibodies ,Neutralizing ,Pandemics ,Betacoronavirus ,COVID-19 ,SARS-CoV-2 ,CD4 ,CD8 ,CXCL10 ,IP-10 ,Spike ,T cells ,adaptive immunity ,antibody ,coronavirus ,epitopes ,neutralizing antibodies ,Pneumonia ,Viral ,Antibodies ,Antigens ,and over ,Neutralizing ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.
- Published
- 2020
28. Targets and cross-reactivity of human T cell recognition of common cold coronaviruses
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Tarke, Alison, Zhang, Yun, Methot, Nils, Narowski, Tara M., Phillips, Elizabeth, Mallal, Simon, Frazier, April, Filaci, Gilberto, Weiskopf, Daniela, Dan, Jennifer M., Premkumar, Lakshmanane, Scheuermann, Richard H., Sette, Alessandro, and Grifoni, Alba
- Published
- 2023
- Full Text
- View/download PDF
29. Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults
- Author
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Rojas, Álvaro, Navarrete, María Soledad, Del Río, Constanza, Del Pino, Dinely, Aguirre, Natalia, Salinas, Grecia, Vega, Franco, Salgado, Acsa, Quinteros, Thomas, Ortiz, Marlene, Puente, Marcela, Muñoz, Alma, Astudillo, Patricio, Le Corre, Nicole, Potin, Marcela, Catalán, Juan, Peralta, Melan, Zamanillo, Consuelo, Keller, Nicole, Fernández, Rocío, Aljaro, Sofía, López, Sofía, González, José Tomás, Weil, Tania, Opazo, Luz, Muñoz, Paula, Estay, Inés, Cantillana, Miguel, Carrera, Liliana, Masalleras, Matías, Guzmán, Paula, Aguirre, Francisca, Cortés, Aarón, Bátiz, Luis Federico, Pérez, Javiera, Apablaza, Karen, Yates, Lorena, Valdés, María de los Ángeles, Hurtado, Bernardita, Venteneul, Veronique, Astorga, Constanza, Muñoz-Venturelli, Paula, Vial, Pablo A., Schilling, Andrea, Pavez, Daniela, Pérez, Inia, Riviotta, Amy, González, Francisca, Urrutia, Francisca, Del Río, Alejandra, Asenjo, Claudia, Vargas, Bárbara, Castro, Francisca, Acuña, Alejandra, Guzmán, Javiera, Astudillo, Camila, Pérez, Carlos M., Espinoza, Pilar, Martínez, Andrea, Arancibia, Marcela, Romero, Harold, Bustamante, Cecilia, Pérez, María Loreto, Uribe, Natalia, Silva, Viviana, Morice, Bernardita, Pérez, Marco, González, Marcela, Jensen, Werner, Pasten, Claudia, Aguilera, M. Fernanda, Martínez, Nataly, Molina, Camila, Arrieta, Sebastián, López, Begoña, Ortiz, Claudia, Escobar, Macarena, Bustamante, Camila, Espinoza, Marcia, Pardo, Angela, Carrasco, Alison, Montes, Miguel, Saldías, Macarena, Gutiérrez, Natalia, Sánchez, Juliette, Fuentes, Daniela, Calvo, Yolanda, Cepeda, Mariela, Lemus, Rosario, Suárez, Muriel, Armijo, Mercedes, Monsalves, Shirley, Marucich, Constance, Cornejo, Cecilia, Acosta, Ángela, Prado, Xaviera, Yáñez, Francisca, Barroeta, Marisol, López, Claudia, Donato, Paulina, Lasso, Martin, Iturrieta, María, Giraldo, Juan, Gutiérrez, Francisco, Acuña, María, Cascone, Ada, Rojas, Raymundo, Sepúlveda, Camila, Contreras, Mario, Campisto, Yessica, González, Pablo, Quizhpi, Zoila, López, Mariella, Pizzeghello, Vania, Silva, Stephannie, Méndez, Constanza, Peñaloza, Hernán F., Schultz, Bárbara M., Piña-Iturbe, Alejandro, Ríos, Mariana, Moreno-Tapia, Daniela, Pereira-Sánchez, Patricia, Leighton, Diane, Orellana, Claudia, Covarrubias, Consuelo, Gálvez, Nicolás M.S., Soto, Jorge A., Duarte, Luisa F., Rivera-Pérez, Daniela, Vázquez, Yaneisi, Cabrera, Alex, Bustos, Sergio, Iturriaga, Carolina, Urzua, Marcela, Navarrete, María S., Fasce, Rodrigo A., Fernández, Jorge, Mora, Judith, Ramírez, Eugenio, Gaete-Argel, Aracelly, Acevedo, Mónica, Valiente-Echeverría, Fernando, Soto-Rifo, Ricardo, Weiskopf, Daniela, Grifoni, Alba, Sette, Alessandro, Zeng, Gang, Meng, Weining, González-Aramundiz, José V., González, Pablo A., Abarca, Katia, Melo-González, Felipe, Bueno, Susan M., and Kalergis, Alexis M.
- Published
- 2023
- Full Text
- View/download PDF
30. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans
- Author
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Mateus, Jose, Grifoni, Alba, Tarke, Alison, Sidney, John, Ramirez, Sydney I, Dan, Jennifer M, Burger, Zoe C, Rawlings, Stephen A, Smith, Davey M, Phillips, Elizabeth, Mallal, Simon, Lammers, Marshall, Rubiro, Paul, Quiambao, Lorenzo, Sutherland, Aaron, Yu, Esther Dawen, da Silva Antunes, Ricardo, Greenbaum, Jason, Frazier, April, Markmann, Alena J, Premkumar, Lakshmanane, de Silva, Aravinda, Peters, Bjoern, Crotty, Shane, Sette, Alessandro, and Weiskopf, Daniela
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Pneumonia & Influenza ,Lung ,Infectious Diseases ,Pneumonia ,Vaccine Related ,Emerging Infectious Diseases ,Biotechnology ,Prevention ,Biodefense ,Good Health and Well Being ,Betacoronavirus ,Blood Donors ,CD4-Positive T-Lymphocytes ,COVID-19 ,Coronavirus Infections ,Cross Reactions ,Epitope Mapping ,Epitopes ,T-Lymphocyte ,Genome ,Viral ,Humans ,Immunologic Memory ,Open Reading Frames ,Pandemics ,Pneumonia ,Viral ,SARS-CoV-2 ,Sequence Homology ,General Science & Technology - Abstract
Many unknowns exist about human immune responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2-reactive CD4+ T cells have been reported in unexposed individuals, suggesting preexisting cross-reactive T cell memory in 20 to 50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4+ T cell repertoire. We demonstrate a range of preexisting memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses human coronavirus (HCoV)-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in coronavirus disease 2019 (COVID-19) disease.
- Published
- 2020
31. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals
- Author
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Grifoni, Alba, Weiskopf, Daniela, Ramirez, Sydney I, Mateus, Jose, Dan, Jennifer M, Moderbacher, Carolyn Rydyznski, Rawlings, Stephen A, Sutherland, Aaron, Premkumar, Lakshmanane, Jadi, Ramesh S, Marrama, Daniel, de Silva, Aravinda M, Frazier, April, Carlin, Aaron F, Greenbaum, Jason A, Peters, Bjoern, Krammer, Florian, Smith, Davey M, Crotty, Shane, and Sette, Alessandro
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Pneumonia ,Immunization ,Lung ,Emerging Infectious Diseases ,Prevention ,Pneumonia & Influenza ,Biodefense ,Infectious Diseases ,Vaccine Related ,Infection ,Good Health and Well Being ,Betacoronavirus ,CD4-Positive T-Lymphocytes ,CD8-Positive T-Lymphocytes ,COVID-19 ,COVID-19 Vaccines ,Convalescence ,Coronavirus Infections ,Cross Reactions ,Epitopes ,T-Lymphocyte ,Humans ,Leukocytes ,Mononuclear ,Pandemics ,Pneumonia ,Viral ,SARS-CoV-2 ,Spike Glycoprotein ,Coronavirus ,Viral Proteins ,Viral Vaccines ,CD4 ,CD8 ,T cells ,coronavirus ,cross-reactivity ,epitopes ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide "megapools," circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4+ T cells in ∼40%-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating "common cold" coronaviruses and SARS-CoV-2.
- Published
- 2020
32. Impact of SARS-CoV-2 exposure history on the T cell and IgG response
- Author
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Keeton, Roanne, Tincho, Marius B., Suzuki, Akiko, Benede, Ntombi, Ngomti, Amkele, Baguma, Richard, Chauke, Masego V., Mennen, Mathilda, Skelem, Sango, Adriaanse, Marguerite, Grifoni, Alba, Weiskopf, Daniela, Sette, Alessandro, Bekker, Linda-Gail, Gray, Glenda, Ntusi, Ntobeko A.B., Burgers, Wendy A., and Riou, Catherine
- Published
- 2023
- Full Text
- View/download PDF
33. Unaltered T cell responses to common antigens in individuals with Parkinson's disease
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Williams, Gregory P., Muskat, Kaylin, Frazier, April, Xu, Yaqian, Mateus, José, Grifoni, Alba, da Silva Antunes, Ricardo, Weiskopf, Daniela, Amara, Amy W., Standaert, David G., Goldman, Jennifer G., Litvan, Irene, Alcalay, Roy N., Sulzer, David, Lindestam Arlehamn, Cecilia S., and Sette, Alessandro
- Published
- 2023
- Full Text
- View/download PDF
34. T-B coculture assay for functional analysis of antigen-specific memory CD4+ T cells
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Ansari, Asgar, primary, Coshic, Poonam, additional, Sharma, Ashok, additional, Sette, Alessandro, additional, Weiskopf, Daniela, additional, and Gupta, Nimesh, additional
- Published
- 2024
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35. Inactivated whole-virion vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern
- Author
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Vikkurthi, Rajesh, Ansari, Asgar, Pai, Anupama R., Jha, Someshwar Nath, Sachan, Shilpa, Pandit, Suvechchha, Nikam, Bhushan, Kalia, Anurag, Jit, Bimal Prasad, Parray, Hilal Ahmad, Singh, Savita, Kshetrapal, Pallavi, Wadhwa, Nitya, Shrivastava, Tripti, Coshic, Poonam, Kumar, Suresh, Sharma, Pragya, Sharma, Nandini, Taneja, Juhi, Pandey, Anil K., Sharma, Ashok, Thiruvengadam, Ramachandran, Grifoni, Alba, Weiskopf, Daniela, Sette, Alessandro, Bhatnagar, Shinjini, and Gupta, Nimesh
- Published
- 2022
- Full Text
- View/download PDF
36. Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment
- Author
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Bosteels, Cedric, Van Damme, Karel F.A., De Leeuw, Elisabeth, Declercq, Jozefien, Maes, Bastiaan, Bosteels, Victor, Hoste, Levi, Naesens, Leslie, Debeuf, Nincy, Deckers, Julie, Cole, Basiel, Pardons, Marion, Weiskopf, Daniela, Sette, Alessandro, Weygaerde, Yannick Vande, Malfait, Thomas, Vandecasteele, Stefaan J., Demedts, Ingel K., Slabbynck, Hans, Allard, Sabine, Depuydt, Pieter, Van Braeckel, Eva, De Clercq, Jozefien, Martens, Liesbet, Dupont, Sam, Seurinck, Ruth, Vandamme, Niels, Haerynck, Filomeen, Roychowdhury, Debasish F., Vandekerckhove, Linos, Guilliams, Martin, Tavernier, Simon J., and Lambrecht, Bart N.
- Published
- 2022
- Full Text
- View/download PDF
37. Anlage 6: FAQ
- Author
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
38. Anlage 3: Beispielhafte Betriebsanweisungen
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
39. Anlage 1: Verordnung zum Schutz der Beschäftigten vor Gefährdungen durch künstliche optische Strahlung (Arbeitsschutzverordnung zu künstlicher optischer Strahlung – OStrV)
- Author
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
40. Beispiele für Gefährdungsbeurteilungen verschiedener Anwendungsbereiche
- Author
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
41. Die Gefährdungsbeurteilung
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
42. Technische und bauliche Schutzmaßnahmen
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
43. Show- und Projektionslaser
- Author
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
44. Gefährdungen durch Laserstrahlung
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
45. Biologische Wirkung von Laserstrahlung
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
46. Unterweisung
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
47. Messungen von Laserstrahlung und Geräte
- Author
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
48. Persönliche Schutzausrüstung (PSA), insbesondere Schutzbrillen
- Author
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
49. Expositionsgrenzwerte (EGW)
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
50. Organisatorische Schutzmaßnahmen
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Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, Weiskopf, Daniela, Schneeweiss, Claudia, Eichler, Jürgen, Brose, Martin, and Weiskopf, Daniela
- Published
- 2020
- Full Text
- View/download PDF
Catalog
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