Search

Your search keyword '"Linterman, Michelle A [0000-0001-6047-1996]"' showing total 9 results
Start Over Author "Linterman, Michelle A [0000-0001-6047-1996]"
9 results on '"Linterman, Michelle A [0000-0001-6047-1996]"'

1. Accelerated waning of the humoral response to COVID-19 vaccines in obesity

Author

van der Klaauw, Agatha A, Horner, Emily C, Pereyra-Gerber, Pehuén, Agrawal, Utkarsh, Foster, William S, Spencer, Sarah, Vergese, Bensi, Smith, Miriam, Henning, Elana, Ramsay, Isobel D, Smith, Jack A, Guillaume, Stephane M, Sharpe, Hayley J, Hay, Iain M, Thompson, Sam, Innocentin, Silvia, Booth, Lucy H, Robertson, Chris, McCowan, Colin, Kerr, Steven, Mulroney, Thomas E, O'Reilly, Martin J, Gurugama, Thevinya P, Gurugama, Lihinya P, Rust, Maria A, Ferreira, Alex, Ebrahimi, Soraya, Ceron-Gutierrez, Lourdes, Scotucci, Jacopo, Kronsteiner, Barbara, Dunachie, Susanna J, Klenerman, Paul, PITCH Consortium, Park, Adrian J, Rubino, Francesco, Lamikanra, Abigail A, Stark, Hannah, Kingston, Nathalie, Estcourt, Lise, Harvala, Heli, Roberts, David J, Doffinger, Rainer, Linterman, Michelle A, Matheson, Nicholas J, Sheikh, Aziz, Farooqi, I Sadaf, Thaventhiran, James ED, University of St Andrews. School of Medicine, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Population and Behavioural Science Division, van der Klaauw, Agatha A [0000-0001-6971-8828], Horner, Emily C [0000-0003-2226-1028], Agrawal, Utkarsh [0000-0001-5181-6120], Foster, William S [0000-0002-7103-3657], Ramsay, Isobel D [0000-0002-9954-2023], Smith, Jack A [0000-0001-6654-5706], Guillaume, Stephane M [0000-0003-2007-4608], Sharpe, Hayley J [0000-0002-4723-298X], Hay, Iain M [0000-0002-5451-1768], McCowan, Colin [0000-0002-9466-833X], O'Reilly, Martin J [0000-0003-1095-0328], Ferreira, Alex [0000-0002-1964-1049], Kronsteiner, Barbara [0000-0003-0867-2867], Dunachie, Susanna J [0000-0001-5665-6293], Klenerman, Paul [0000-0003-4307-9161], Park, Adrian J [0000-0003-2713-7595], Linterman, Michelle A [0000-0001-6047-1996], Matheson, Nicholas J [0000-0002-3318-1851], Sheikh, Aziz [0000-0001-7022-3056], Farooqi, I Sadaf [0000-0001-7609-3504], Thaventhiran, James ED [0000-0001-8616-074X], and Apollo - University of Cambridge Repository

Subjects
MCC, COVID-19 Vaccines, SARS-CoV-2, Vaccination, COVID-19, DAS, Antibodies, Viral, Antibodies, Neutralizing, Obesity, Morbid, SDG 3 - Good Health and Well-being, RA0421, RA0421 Public health. Hygiene. Preventive Medicine, Humans, Longitudinal Studies, Prospective Studies, Obesity
Abstract

Funding: EAVE II is funded by the Medical Research Council (MRC) (MC_PC_19075) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20058) and National Core Studies–Immunity. Additional support was provided through Public Health Scotland, the Scottish Government Director-General Health and Social Care and the University of Edinburgh. The SCORPIO study was supported by the MRC (MR/W020564/1, a core award to J.E.T.; MC_UU_0025/12 and MR/T032413/1, awards to N.J.M.) and the Medical Research Foundation (MRF-057-0002-RG-THAV-C0798). Additional support was provided by NHS Blood and Transplant (WPA15-02 to N.J.M.), the Wellcome Trust (Institutional Strategic Support Fund 204845/Z/16/Z to N.J.M.), Addenbrooke’s Charitable Trust (900239 to N.J.M.) and the NIHR Cambridge Biomedical Research Centre and NIHR BioResource. M.A.L is supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (BBS/E/B/000C0427 and BBS/E/B/000C0428) and is a Lister Institute Fellow and an EMBO Young Investigator. I.M.H. is supported by a Cambridge Institute for Medical Research PhD studentship. H.J.S. is supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (109407), and a BBSRC institutional program grant (BBS/E/B/000C0433). I.S.F. is supported by the Wellcome Trust (207462/Z/17/Z), the Botnar Fondation, the Bernard Wolfe Health Neuroscience Endowment and an NIHR Senior Investigator Award. Obesity is associated with an increased risk of severe Coronavirus Disease 2019 (COVID-19) infection and mortality. COVID-19 vaccines reduce the risk of serious COVID-19 outcomes; however, their effectiveness in people with obesity is incompletely understood. We studied the relationship among body mass index (BMI), hospitalization and mortality due to COVID-19 among 3.6 million people in Scotland using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. We found that vaccinated individuals with severe obesity (BMI > 40 kg/m2) were 76% more likely to experience hospitalization or death from COVID-19 (adjusted rate ratio of 1.76 (95% confidence interval (CI), 1.60–1.94). We also conducted a prospective longitudinal study of a cohort of 28 individuals with severe obesity compared to 41 control individuals with normal BMI (BMI 18.5–24.9 kg/m2). We found that 55% of individuals with severe obesity had unquantifiable titers of neutralizing antibody against authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus compared to 12% of individuals with normal BMI (P = 0.0003) 6 months after their second vaccine dose. Furthermore, we observed that, for individuals with severe obesity, at any given anti-spike and anti-receptor-binding domain (RBD) antibody level, neutralizing capacity was lower than that of individuals with a normal BMI. Neutralizing capacity was restored by a third dose of vaccine but again declined more rapidly in people with severe obesity. We demonstrate that waning of COVID-19 vaccine-induced humoral immunity is accelerated in individuals with severe obesity. As obesity is associated with increased hospitalization and mortality from breakthrough infections, our findings have implications for vaccine prioritization policies. Publisher PDF

Published
2023

2. Sec22b is a critical and non-redundant regulator of plasma cell maintenance

Author

Amélie Bonaud, Laetitia Gargowitsch, Simon M. Gilbert, Elanchezhian Rajan, Pablo Canales-Herrerias, Daniel Stockholm, Nabila F. Rahman, Mark O. Collins, Hakan Taskiran, Danika L. Hill, Andres Alloatti, Nagham Alouche, Stéphanie Balor, Vanessa Soldan, Daniel Gillet, Julien Barbier, Françoise Bachelerie, Kenneth G. C. Smith, Julia Jellusova, Pierre Bruhns, Sebastian Amigorena, Karl Balabanian, Michelle A. Linterman, Andrew A. Peden, Marion Espéli, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Inflammation, microbiome, immunosurveillance (MI2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Cambridge [UK] (CAM), University of Sheffield [Sheffield], Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), School of Psychology [Cardiff University], Cardiff University, Technische Universität München = Technical University of Munich (TUM), Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, The Babraham Institute [Cambridge, UK], Monash University [Melbourne], Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad Nacional de Rosario [Santa Fe], Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-19-CE15-0019,PC-SEC,Impact des SNARE sur la biologie des plasmocytes(2019), ANR-14-ACHN-0008,AUTO-PLASMO,Analyse integrative de la biologie des plasmocytes normaux et pathologiques(2014), ANR-17-CE14-0019,OSTEOVALYMPH,Autocrinie et paracrinie de l'axe de signalisation CXCL12/CXCR4-CXCR7 dans la niche ostéo-vasculaire: impact sur la spécification et l'engagement lymphoïde des cellules souches hématopoïétiques(2017), ANR-18-CE15-0001,Autoimmuni-B,Etude de la rupture de tolérance dans une maladie humaine autoimmune médiée par les lymphocytes B(2018), The study was supported by the Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LabEx LERMIT) (M.E. and K.B.), an ANR JCJC grant (ANR-19-CE15-0019-01), an ANR @RAction grant (ANR-14-ACHN-0008), a 'Fondation ARC pour la recherche sur le cancer' grant (P JA20181208173), and a grant from IdEx Université Paris-Cité (ANR-18-IDEX-0001) to M.E., and an ANR PRC grant (ANR-17-CE14-0019) and an INCa grant (PRT-K 2017) to K.B. P.B. acknowledges funding from the French National Research Agency grant ANR-18-CE15-0001 project Autoimmuni-B, by the Institut Carnot Pasteur Microbes et Santé grant ANR-11-CARN-0017-01, the Institut Pasteur, and the Institut National de la Santé et de la Recherche Médicale (INSERM). M.A.L. is supported by Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0427, BBS/E/B/000C0428, and the Campus Capability Core Grant to the Babraham Institute). A.A.P. and M.O.C. were supported by a grant from the Biotechnology and Biological Sciences Research Council (BB/L022389/1). D.L.H. is supported by a National Health and Medical Research Council Australia Early-Career Fellowship (APP1139911). N.A. was supported by a PhD fellowship from the French Ministry for education and by a fourth year PhD fellowship from the 'Fondation ARC pour la recherche sur le cancer.' P.C.-H. was supported partly by a stipend from the Pasteur-Paris University (PPU) International PhD program, and by a fellowship from the French Fondation pour la Recherche Médicale (FRM). K.G.C.S. was supported by the Wellcome Trust (Programme Grant Number 083650/Z/07/Z). J.J’s research is supported by the German Research Foundation project number: 419193696 and through the CRC1335. H.T. is supported through the graduate school of the Max Planck Institute for Immunobiology and Epigenetics (IMPRS-IE) and through the CRC1335. The 'EMiLy' U1160 INSERM unit is a member of the OPALE Carnot institute, The Organization for Partnerships in Leukemia (Institut Carnot OPALE, Institut de Recherche Saint-Louis, Hôpital Saint-Louis, Paris, France. Web: www.opale.org. Email: contact@opale.org)., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Bonaud, Amélie [0000-0002-4153-9171], Rajan, Elanchezhian [0000-0002-6257-3678], Canales-Herrerias, Pablo [0000-0002-1865-6476], Stockholm, Daniel [0000-0002-5069-5256], Collins, Mark O [0000-0002-7656-4975], Taskiran, Hakan [0000-0002-2690-3887], Alloatti, Andres [0000-0003-0555-0653], Gillet, Daniel [0000-0003-0477-3599], Bruhns, Pierre [0000-0002-4709-8936], Balabanian, Karl [0000-0002-0534-3198], Linterman, Michelle A [0000-0001-6047-1996], Peden, Andrew A [0000-0003-0144-7712], Espéli, Marion [0000-0001-5005-1664], and Apollo - University of Cambridge Repository

Subjects
R-SNARE Proteins, mitochondria, Mice, endoplasmic reticulum, Multidisciplinary, plasma cell, SNARE, antibody, [SDV]Life Sciences [q-bio], Plasma Cells, Animals, Biological Transport, SNARE Proteins
Abstract

Despite the essential role of plasma cells in health and disease, the cellular mechanisms controlling their survival and secretory capacity are still poorly understood. Here, we identified the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Sec22b as a unique and critical regulator of plasma cell maintenance and function. In the absence of Sec22b, plasma cells were hardly detectable and serum antibody titers were dramatically reduced. Accordingly, Sec22b -deficient mice fail to mount a protective immune response. At the mechanistic level, we demonstrated that Sec22b contributes to efficient antibody secretion and is a central regulator of plasma cell maintenance through the regulation of their transcriptional identity and of the morphology of the endoplasmic reticulum and mitochondria. Altogether, our results unveil an essential and nonredundant role for Sec22b as a regulator of plasma cell fitness and of the humoral immune response.

Published
2023
Full Text
View/download PDF

3. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Author

Collier, D. A., Ferreira, I. A. T. M., Kotagiri, P., Datir, R. P., Lim, E. Y., Touizer, E., Meng, B., Abdullahi, A., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Maxwell, P., Shaw, A., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Gleadall, N., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Krishna, B., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Potts, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., D. D. De Bie E. M., Bunclark, K., Josipovic, M., Mackay, M., Michael, A., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Smith, K. G. C., Bradley, J. R., Ceron-Gutierrez, L., Cortes-Acevedo, P., Barcenas-Morales, G., Linterman, M. A., Mccoy, L. E., Davis, C., Thomson, E., Mckinney, E., Doffinger, R., Wills, M., Gupta, R. K., Collier, Dami A [0000-0001-5446-4423], Datir, Rawlings P [0000-0003-0521-2144], Smith, Kenneth GC [0000-0003-3829-4326], Linterman, Michelle A [0000-0001-6047-1996], McCoy, Laura E [0000-0001-9503-7946], Thomson, Emma [0000-0003-1482-0889], Lyons, Paul A [0000-0001-7035-8997], Gupta, Ravindra K [0000-0001-9751-1808], and Apollo - University of Cambridge Repository

Subjects
Male, 0301 basic medicine, Aging, Secondary, T-Lymphocytes, Antibodies, Viral, Neutralization, 0302 clinical medicine, 80 and over, Medicine, Viral, Neutralizing, Adult, Aged, Aged, 80 and over, Antibodies, Neutralizing, Autoantibodies, B-Lymphocytes, BNT162 Vaccine, COVID-19 Vaccines, Female, Health Personnel, Humans, Immunization, Secondary, Immunoglobulin A, Immunoglobulin Class Switching, Immunoglobulin G, Immunologic Memory, Inflammation, Interferon-gamma, Interleukin-2, Middle Aged, SARS-CoV-2, Somatic Hypermutation, Immunoglobulin, Spike Glycoprotein, Coronavirus, Vaccination, Vaccines, Synthetic, Immunity, Sars-Cov-2, Vaccines, education.field_of_study, Multidisciplinary, biology, Spike Glycoprotein, 030220 oncology & carcinogenesis, Antibody, Population, Article, Antibodies, 03 medical and health sciences, Immune system, Immunoglobulin, education, business.industry, Synthetic, Somatic Hypermutation, Vaccine efficacy, Coronavirus, 030104 developmental biology, Immunization, Immunology, biology.protein, business
Abstract

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating., Nature, 596 (7872), ISSN:0028-0836, ISSN:1476-4687

Published
2021
Full Text
View/download PDF

4. Impaired HA-specific T follicular helper cell and antibody responses to influenza vaccination are linked to inflammation in humans

Author

Carly E. Whyte, James Dooley, Michelle A. Linterman, James Lee, Jia Le Lee, Martin S. Zand, Silvia Innocentin, Jiong Wang, Edward J. Carr, Danika L. Hill, William W. Kwok, Eddie A. James, Adrian Liston, Hill, Danika L [0000-0001-6284-7061], Carr, Edward J [0000-0001-9343-4593], Linterman, Michelle [0000-0001-6047-1996], Apollo - University of Cambridge Repository, and Linterman, Michelle A [0000-0001-6047-1996]

Subjects
Mouse, QH301-705.5, T cell, Science, Cell, Inflammation, Major histocompatibility complex, General Biochemistry, Genetics and Molecular Biology, t follicular helper cells, Flow cytometry, immunology, 03 medical and health sciences, 0302 clinical medicine, Immunology and Inflammation, medicine, Humans, antibodies, Biology (General), 030304 developmental biology, 0303 health sciences, General Immunology and Microbiology, biology, medicine.diagnostic_test, General Neuroscience, T-cell receptor, Vaccination, General Medicine, vaccines, 3. Good health, medicine.anatomical_structure, Hemagglutinins, Influenza Vaccines, ageing, Immunology, Antibody Formation, biology.protein, Medicine, medicine.symptom, Antibody, influenza, germinal centre, 030215 immunology, Research Article, Human
Abstract

Antibody production following vaccination can provide protective immunity to subsequent infection by pathogens such as influenza viruses. However, circumstances where antibody formation is impaired after vaccination, such as in older people, require us to better understand the cellular and molecular mechanisms that underpin successful vaccination in order to improve vaccine design for at-risk groups. Here, by studying the breadth of anti-haemagglutinin (HA) IgG, serum cytokines, and B and T cell responses by flow cytometry before and after influenza vaccination, we show that formation of circulating T follicular helper (cTfh) cells was associated with high-titre antibody responses. Using Major Histocompatability Complex (MHC) class II tetramers, we demonstrate that HA-specific cTfh cells can derive from pre-existing memory CD4+T cells and have a diverse T cell receptor (TCR) repertoire. In older people, the differentiation of HA-specific cells into cTfh cells was impaired. This age-dependent defect in cTfh cell formation was not due to a contraction of the TCR repertoire, but rather was linked with an increased inflammatory gene signature in cTfh cells. Together, this suggests that strategies that temporarily dampen inflammation at the time of vaccination may be a viable strategy to boost optimal antibody generation upon immunisation of older people.

Published
2021

5. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Author

Collier, Dami A., Ferreira, Isabella A. T. M., Kotagiri, Prasanti, Datir, Rawlings P., Lim, Eleanor Y., Touizer, Emma, Meng, Bo, Abdullahi, Adam, Elmer, Anne, Kingston, Nathalie, Graves, Barbara, Le Gresley, Emma, Caputo, Daniela, Bergamaschi, Laura, Smith, Kenneth G. C., Bradley, John R., Ceron-Gutierrez, Lourdes, Cortes-Acevedo, Paulina, Barcenas-Morales, Gabriela, Linterman, Michelle A., McCoy, Laura E., Davis, Chris, Thomson, Emma, McKinney, Eoin, Doffinger, Rainer, Wills, Mark, Gupta, Ravindra K., Baker, Stephen, Dougan, Gordon, Hess, Christoph, Lehner, Paul J., Lyons, Paul A., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Summers, Charlotte, Thaventhiran, James E. D., Toshner, Mark, Weekes, Michael P., Maxwell, Patrick, Shaw, Ashley, Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, Mescia, Federica, O’Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Betancourt, Ariana, Bower, Georgie, Cossetti, Chiara, De Sa, Aloka, Epping, Madeline, Gleadall, Nick, Grenfell, Richard, Hinch, Andrew, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Krishna, Ben, Lewis, Daniel, Marsden, Joe, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Potts, Martin, Richoz, Nathan, Romashova, Veronika, Yarkoni, Natalia Savinykh, Sharma, Rahul, Stefanucci, Luca, Stephens, Jonathan, Strezlecki, Mateusz, Turner, Lori, D. D. De Bie, Eckart M., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Michael, Alice, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Ansaripour, Ali, Mwaura, Lucy, Patterson, Caroline, Polwarth, Gary, Polgarova, Petra, Di Stefano, Giovanni, Fahey, Codie, Michel, Rachel, Bong, Sze-How, Coudert, Jerome D., Holmes, Elaine, Allison, John, Butcher, Helen, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Gray, Jennifer, Ivers, Tasmin, Kasanicki, Mary, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer, Collier, Dami A. [0000-0001-5446-4423], Datir, Rawlings P. [0000-0003-0521-2144], Smith, Kenneth G. C. [0000-0003-3829-4326], Linterman, Michelle A. [0000-0001-6047-1996], McCoy, Laura E. [0000-0001-9503-7946], Thomson, Emma [0000-0003-1482-0889], Lyons, Paul A. [0000-0001-7035-8997], Gupta, Ravindra K. [0000-0001-9751-1808], and Apollo - University of Cambridge Repository

Subjects
article, 13/106, 38/39, 631/250/2152/2153/1291, 631/326/596/4130, 38
Abstract

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.

Published
2021
Full Text
View/download PDF

6. The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses

Author

Sarina Camuglia, Yan Wang, Kun Qian, Danika L. Hill, Qunxiong Zeng, Kaili Liang, Feng Xue, Tao Zhou, Wim Pierson, Katherine Kedzierska, Qiang Xia, Zhian Chen, W.F. Shen, Di Yu, Fadzai Victor Makota, Lilin Ye, Thi H. O. Nguyen, Nan Shen, Qian Chen, Jun Deng, Hong Sheng Ong, Fan Xiao, Yanmin Wan, Yunbo Wei, Zhanguo Li, Jianyang Ma, Steven Rockman, Xiaohui Wang, Michelle A. Linterman, Xin Gao, Dongcheng Gong, Kaiming Luo, Xiang Yu, Haibo Zhou, Liwei Lu, Lingyun Sun, Jing He, Deng, Jun [0000-0002-8916-6503], Luo, Kaiming [0000-0002-1797-0172], He, Jing [0000-0003-3904-8928], Nguyen, Thi HO [0000-0002-9294-7693], Li, Zhanguo [0000-0002-2590-6242], Qian, Kun [0000-0003-1666-1965], Linterman, Michelle A [0000-0001-6047-1996], Kedzierska, Katherine [0000-0001-6141-335X], Shen, Nan [0000-0002-5875-4417], Lu, Liwei [0000-0002-8634-0967], Yu, Di [0000-0003-1721-8922], and Apollo - University of Cambridge Repository

Subjects
Leptin, 0301 basic medicine, Science, General Physics and Astronomy, Antibodies, Viral, Lymphocyte Activation, Article, Antibodies, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, Immune system, Antigen, Influenza, Human, Animals, Homeostasis, Humans, Vaccines, Multidisciplinary, Leptin Deficiency, biology, digestive, oral, and skin physiology, Vaccination, Lymphocyte differentiation, Cell Differentiation, General Chemistry, Mice, Inbred C57BL, 030104 developmental biology, Influenza Vaccines, Antibody Formation, Immunology, biology.protein, Female, Immunization, Antibody, hormones, hormone substitutes, and hormone antagonists, 030215 immunology
Abstract

Follicular helper T (TFH) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate TFH function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying TFH regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human TFH differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs TFH generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of TFH cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure., T follicular helper (TFH) cell numbers are increased after vaccination and fewer of these cells might result in reduced vaccine responses. Here the authors show in mice and humans that leptin promotes TFH differentiation and that low leptin levels can impair TFH response to vaccines and virus protection in mice.

Published
2021
Full Text
View/download PDF

7. Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ

Author

Sigrid Fra-Bido, Louise S. Matheson, Julien Novarino, Noudjoud Attaf, Silvia Innocentin, Nicolas Fazilleau, Louise M. C. Webb, Alexandre Bignon, Michelle A. Linterman, Benson-Rumiz, Alicia, The Babraham Institute [Cambridge, UK], Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Webb, Louise MC [0000-0003-3417-1484], Fra-Bido, Sigrid [0000-0003-2398-5191], Attaf, Noudjoud [0000-0001-7254-7679], Fazilleau, Nicolas [0000-0002-3574-5614], Linterman, Michelle A [0000-0001-6047-1996], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Receptors, CXCR5, Aging, Notch, T Follicular Helper Cells, Cellular differentiation, Biology, RBPJ, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Animals, Humans, Transcription factor, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, T follicular helper cell differentiation, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Effector, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, T-cell receptor, Cell Differentiation, Cell Biology, Original Articles, Cell biology, CXCR5, 030104 developmental biology, age, Ageing, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Female, Original Article, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

Ageing profoundly changes our immune system and is thought to be a driving factor in the morbidity and mortality associated with infectious disease in older people. We have previously shown that the impaired immunity to vaccination that occurs in aged individuals is partly attributed to the effect of age on T follicular helper (Tfh) cell formation. In this study, we examined how age intrinsically affects Tfh cell formation in both mice and humans. We show increased formation of Tfh precursors (pre‐Tfh) but no associated increase in germinal centre (GC)‐Tfh cells in aged mice, suggesting age‐driven promotion of only early Tfh cell differentiation. Mechanistically, we show that ageing alters TCR signalling which drives expression of the Notch‐associated transcription factor, RBPJ. Genetic or chemical modulation of RBPJ or Notch rescues this age‐associated early Tfh cell differentiation, and increased intrinsic Notch activity recapitulates this phenomenon in younger mice. Our data offer mechanistic insight into the age‐induced changes in T‐cell activation that affects the differentiation and ultimately the function of effector T cells., Ageing alters TCR signalling which drives expression of the Notch‐associated transcription factor, RBPJ. This results in enhanced differentiation into T follicular helper cell precursors.

Published
2020
Full Text
View/download PDF

8. Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination

Author

Ine Vanderleyden, Martin S. Zand, Jonathan Clark, James Dooley, Jiong Wang, Danika L. Hill, Adrian Liston, Michelle A. Linterman, Alyssa Silva-Cayetano, Silvia Innocentin, Marisa Stebegg, Alexandre Bignon, Louis Boon, Edward J. Carr, Christel Krueger, Stebegg, Marisa [0000-0001-8434-8271], Silva-Cayetano, Alyssa [0000-0003-0533-1629], Krueger, Christel [0000-0001-5601-598X], Carr, Edward [0000-0001-9343-4593], Linterman, Michelle A [0000-0001-6047-1996], and Apollo - University of Cambridge Repository

Subjects
Life Sciences & Biomedicine - Other Topics, 0301 basic medicine, Male, Aging, Mouse, Cellular differentiation, Cell, Receptor, Interferon alpha-beta, immunology, DOUBLE-BLIND, Mice, 0302 clinical medicine, Immunology and Inflammation, TOPICAL IMIQUIMOD, IMMUNE-RESPONSE, Medicine, Biology (General), Mice, Knockout, B-Lymphocytes, biology, General Neuroscience, Vaccination, General Medicine, T-Lymphocytes, Helper-Inducer, Middle Aged, Adoptive Transfer, ANTIBODY-PRODUCTION, 3. Good health, medicine.anatomical_structure, TRIVALENT INFLUENZA VACCINE, Influenza Vaccines, B-CELLS, Female, Antibody, Life Sciences & Biomedicine, Research Article, Human, Trivalent influenza vaccine, Adult, Adolescent, T Follicular Helper Cells, GERMINAL CENTER DEVELOPMENT, QH301-705.5, Science, Antigen presentation, Bone Marrow Cells, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Young Adult, Immune system, I IFN, Orthomyxoviridae Infections, Influenza, Human, ANTIGEN PRESENTATION, Animals, Humans, dendritic cells, germinal centre response, Biology, Aged, Science & Technology, General Immunology and Microbiology, business.industry, CD11 Antigens, Chimera, Germinal center, Germinal Center, Immunity, Humoral, 030104 developmental biology, inflammation, ageing, Immunology, Humoral immunity, biology.protein, business, Immunologic Memory, ELDERLY INDIVIDUALS, 030215 immunology
Abstract

Germinal centres (GCs) are T follicular helper cell (Tfh)-dependent structures that form in response to vaccination, producing long-lived antibody secreting plasma cells and memory B cells that protect against subsequent infection. With advancing age the GC and Tfh cell response declines, resulting in impaired humoral immunity. We sought to discover what underpins the poor Tfh cell response in ageing and whether it is possible to correct it. Here, we demonstrate that older people and aged mice have impaired Tfh cell differentiation upon vaccination. This deficit is preceded by poor activation of conventional dendritic cells type 2 (cDC2) due to reduced type 1 interferon signalling. Importantly, the Tfh and cDC2 cell response can be boosted in aged mice by treatment with a TLR7 agonist. This demonstrates that age-associated defects in the cDC2 and Tfh cell response are not irreversible and can be enhanced to improve vaccine responses in older individuals. ispartof: ELIFE vol:9 ispartof: location:England status: published

Published
2020
Full Text
View/download PDF

9. Type I interferon induces CXCL13 to support ectopic germinal center formation

Author

Barry Bradford, Joanna R Groom, Edward J. Carr, Burkhard Ludewig, Urs Mörbe, Neil A. Mabbott, Fanny Lafouresse, Silvia Innocentin, Kim L. Good-Jacobson, Michelle A. Linterman, Alice E. Denton, Denton, Alice E [0000-0002-4580-3443], Carr, Edward J [0000-0001-9343-4593], Bradford, Barry M [0000-0002-4007-1685], Lafouresse, Fanny [0000-0001-6572-8631], Mabbott, Neil A [0000-0001-7395-1796], Mörbe, Urs [0000-0001-8747-437X], Ludewig, Burkhard [0000-0002-7685-573X], Groom, Joanna R [0000-0001-5251-7835], Good-Jacobson, Kim L [0000-0003-1891-7274], Linterman, Michelle A [0000-0001-6047-1996], Apollo - University of Cambridge Repository, and BBSRC

Subjects
0301 basic medicine, INFLUENZA-VIRUS, Male, Research & Experimental Medicine, T-CELL, T-Lymphocytes, Regulatory, 0302 clinical medicine, Interferon, Immunology and Allergy, Lung, Research Articles, 11 Medical and Health Sciences, education.field_of_study, B-Lymphocytes, ABSENCE, 3. Good health, Lymphatic system, Medicine, Research & Experimental, 030220 oncology & carcinogenesis, CHEMOKINE RECEPTOR, Interferon Type I, Female, Life Sciences & Biomedicine, medicine.drug, Receptors, CXCR5, LYMPHOID-TISSUE IBALT, B-cell receptor, Population, education, Immunology, Context (language use), Mice, Transgenic, Biology, Article, 03 medical and health sciences, Orthomyxoviridae Infections, medicine, C-MYC, Animals, B-CELL RECEPTOR, CXCL13, Science & Technology, MEMORY, Germinal center, Interferon-beta, Fibroblasts, Germinal Center, Chemokine CXCL13, Mice, Inbred C57BL, 030104 developmental biology, Cancer research, INNATE IMMUNITY, Interferon type I, RESPONSES
Abstract

Denton et al. show that during influenza infection of mice, type I interferon can induce CXCL13 de novo in pulmonary PGDFRα+ fibroblasts. This chemokine drives CXCR5-dependent recruitment of B cells to the lung, thereby supporting pulmonary germinal center formation., Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context of infection, this response can be beneficial for the host: influenza A virus infection–induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite the ubiquity of ectopic lymphoid structures and their role in both health and disease, little is known about the mechanisms by which inflammation is able to convert a peripheral tissue into one that resembles a secondary lymphoid organ. Here, we show that type I IFN produced after viral infection can induce CXCL13 expression in a phenotypically distinct population of lung fibroblasts, driving CXCR5-dependent recruitment of B cells and initiating ectopic germinal center formation. This identifies type I IFN as a novel inducer of CXCL13, which, in combination with other stimuli, can promote lung remodeling, converting a nonlymphoid tissue into one permissive to functional tertiary lymphoid structure formation., Graphical Abstract

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results