Dr. Nina Le Bert, Senior Research Fellow at Duke-NUS Medical School, Singapore.

Dr. Nina Le Bert, Senior Research Fellow at Duke-NUS Medical School, Singapore.

This is a summary of the curriculum vitae (CV) of Dr. Nina Le Bert, PhD, Senior Research Fellow in the Program in Emerging Infectious Diseases at Duke-NUS Medical School, Singapore. On April 22, she will give a presentation at Fujita Health University about T cell immunity after COVID-19 infection or vaccination.

Dr. Le Bert is a human immunologist with a specific interest in the role of antigen-specific T and B cells in control and pathogenesis of viral infections.

She is a member of the research group of Professor Antonio Bertoletti at Duke-NUS Medical School since 2014. This group used to be specialized in T cell immunity against hepatitis B virus (HBV), but since the COVID-19 pandemic has been studying T cell immunity against the COVID-19 virus (SARS-CoV-2). Although the group is not big, they can probably be considered among the top five groups worldwide in studying this very important topic. Dr. Le Bert is a senior member of the group, and on T cell immunity in COVID-19 has first-author papers in Nature and Journal of Experimental Medicine. International recognition of her work was expressed in 2021 by her receiving of, together with Prof. Bertoletti, the Boulle-SEI International Award from the Spanish Society of Immunology.

Dr. Le Bert is from Germany and studied Biology at the University of Berlin. She was awarded a Marie Curie Early Stage Research Fellowship allowing her to train as a PhD student at the Division of Infection & Immunity at the University College London (UK). During this time, she studied how differential priming of dendritic cells alters the profile of T cell functions. In 2012 she moved to Singapore, joining initially Dr. Stephan Gasser’s laboratory at the National University of Singapore, investigating the role of cytosolic DNA in immune activation. Since 2014 she is working in Prof. Bertoletti’s laboratory at Duke-NUS Medical School.

In Prof. Bertoletti’s lab, as for Hepatitis B virus (HBV) infection, together with a PhD student under her supervision, Dr. Le Bert demonstrated that HBsAg-specific B cells are dysfunctional in chronic HBV infection (Salimzadeh, Le Bert et al., The Journal of Clinical Investigation, 2018). Moreover, she established that HBV-specific T cells associate with viral control upon therapy discontinuation in chronic HBV patients (Rivino, Le Bert et al., The Journal of Clinical Investigation, 2018). In addition, she showed that rather the duration than the quantity of HBsAg associates with deletion and exhaustion of HBsAg-specific T cells in chronic HBV patients (Le Bert, Gill, Hong et al., Gastroenterology, 2020).

Since the beginning of the COVID-19 pandemic, her research has been focused on the characterization of SARS-CoV2-specific T cell responses in COVID-19 and SARS convalescents and in various cohorts of individuals pre and post vaccination. She first showed that SARS-CoV-2 induces robust T cell responses and that infection with coronaviruses induces long-lasting memory T cells. Furthermore, the team observed that early and highly functional virus-specific T cells correlate with rapid viral clearance and asymptomatic/mild infections. In addition, their induction by vaccination correlates with the onset of vaccine efficacy, hence all advocating for a protective role of T cells. The development of a rapid test allows to monitor the cellular immune response in large populations, which revealed highly variable T cell responses to vaccination and infection within greatly homologous cohorts.

In the coming years she is interested in pursuing three areas: 1) Exploit T cells in therapy against viral diseases; 2) Define correlates of antigen-specific T cell function in viral infections with protection leading to diagnostic tests for clinical management; 3) Study the underlying causes for variable immune responses to vaccination and infection.

I am very happy and grateful that she will give a presentation at Fujita Health University. Immune memory against viruses derives from both B cells (antibodies) and T cells, and in many instances the latter are more important. Many researchers study antibody responses against COVID-19 viruses and vaccines, but relatively few researchers study T cell responses because those are more difficult to investigate. Therefore, listening to Dr. Le Bert will be a unique opportunity for us to learn how this critical arm of the immune system helps our bodies fight the ongoing pandemic.

 

CURRICULUM VITAE

 

EDUCATION:

1999-2005          Freie Universität Berlin, Germany

                               Bachelor’s and Master’s Degree (Diplom) in Biological Sciences; Grade 1 (first

                               class). Main subjects: Microbiology, Genetics, Biochemistry and Molecular

                               Biology, and Biopsychology

2002-2003           University of Wales, Swansea, UK

                               Study at the Institute of Life Sciences (Socrates/Erasmus Scholarship)

                               Modules: Cell- and Immuno-Biology, Immunology Concepts, Applied

                               Immunology, Microbial Genetics, Gene Manipulation, Human and Medical

                               Genetics, Physiology and Biochemistry of Neurons, Neuroscience

2004-2005          Freie Universität Berlin, Germany & Université Pierre et Marie Curie, Paris,

                               France. Master’s Thesis at the Institute of Biology; Grade 1 (first class) (DAAD

                               Fellowship). Supervisors: Prof. Günter Korge, Dr. Günther Roth and Dr. Chantal

                               Dauphin-Villemanth

2006-2011          University College London, UK

                                PhD at the Division of Infection & Immunity (Marie Curie Early Stage Research

                               Fellowship). Supervisors: Prof. Graham Rook and Dr. Mahdad Noursadeghi

                                Title: Dendritic cell mediated modulation of immune responses by

                                Mycobacterium vaccae

 

PROFESSIONAL EXPERIENCE:

2005-2006          Ernst & Young (EY), Mannheim, Germany

                               Assistant Biotechnology Analyst, Health Sciences Team

                               •  Market Research: German Biotechnology Report 2006 and the European

                               part of the Global Biotechnology Report 2006; Responsibilities: Article writing

                               about emerging biotechnologies and markets, composition and evaluation of

                               questionnaires, data administration with MS-Access, data analysis and

                               appraisal of research results, internet research, communication with biotech

                               companies on national and international level

2012-2014          Research Fellow, Immunology Programme, Department of Microbiology,

                               National University of Singapore

                               Supervisor: A/P Dr Stephan Gasser

                               •  Role of cytosolic DNA in cancer cells and the downstream signal

                                 transduction leading to immune recognition

                               •  Primary cell culture (human and animal), animal work, molecular work,

                                 lentiviral transduction, live-cell imaging

2014-2017          Research Fellow, Program in Emerging Infectious Diseases, Singapore

                               Institute for Clinical Sciences, A*STAR and DUKE-NUS Medical School,

                               Singapore

                               Supervisor: Professor Antonio Bertoletti

                               •  Role of HBsAg on global and HBV-specific T cells

                               •  HBV-specific T cells during treatment discontinuation in chronic HBV

                               •  Manage collaborations with Gilead Sciences, and clinical and academic

                                  collaborators in Singapore and abroad

                               •  Supervision of PhD students and technical assistants

2017-present      Senior Research Fellow, Program in Emerging Infectious Diseases, Duke-

                               NUS Medical School, Singapore

                               Supervisor: Professor Antonio Bertoletti

                               •  Characterisation of SARS-CoV-2-specific T cells in COVID-19 and SARS

                                  patients

                               •  Development of high-throughput diagnostic assays for quantification of

                                  virus-specific T cells

                               •  Characterisation of HBV-specific B and T cells in chronic and acute HBV

                                  infection

                               •  Managing industry collaborations with Brii-Biosciences, SpringBank and

                                   Gilead Sciences, as well as clinical and academic collaborations in

                                   Singapore and abroad

                               •  Supervision of Research fellows, PhD students and technical assistants

 

FELLOWSHIPS & AWARDS:

2002                 Socrates/Erasmus Scholarship

2004                 DAAD Fellowship (German Academic Exchange Service)

2006                 Marie Curie Early Stage Research Fellowship

2021                 Boulle-SEI International Award – Spanish Society of Immunology

2021                 SingHealth & Duke-NUS Research Team Award

 

MEMBERSHIPS:

2008-2011            British Society for Immunology

2012-present       Singaporean Society for Immunology – Council Member

2021-present       Women in Science Career Advancement Programme, Duke-NUS Medical

                                 School

2021-present       Emerging Scholar Scientific and Medical Advisory Board (eSAMB) of the

                                Hepatitis B Foundation

 

PATENTS:

2021                 Bertoletti A, Tan AT, Le Bert N (PCT/SG2021/050627 filed on 18 October 2021) A

                             method to monitor virus-specific T cells in biological samples.

 

MOST IMPORTANT PUBLICATIONS

(* equal contribution)

1. *Rivino L, *Le Bert N, Gill US, Kunasegaran K, Cheng Y, Tan D, Becht E, Hansi NK, Foster GR, Su TH, Tseng TC, Lim SG, Kao JH, Newell EW, Kennedy PTF, Bertoletti A. 2018. Hepatitis B virus–specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation. The Journal of Clinical Investigation 128:668-681

2. *Salimzadeh L, *Le Bert N, Dutertre CA, Gill US, Newell EW, Frey C, Hung M, Novikov N, Fletcher S, Kennedy PTF, Bertoletti A. 2018. PD-1 blockade partially recovers dysfunctional virus–specific B cells in chronic hepatitis B infection. The Journal of Clinical Investigation 128:4573-4587

3. *Le Bert N, *Salimzadeh L, Gill US, Dutertre CA, Facchetti F, Tan A, Hung M, Novikov N, Lampertico P, Fletcher SP, Kennedy PTF, Bertoletti A. 2020. Comparative characterization of B cells specific for HBV nucleocapsid and envelope proteins in patients with chronic hepatitis B. Journal of Hepatology 72:34-44

4. *Le Bert N, *Gill US, *Hong M, Kunasegaran K, Tan DZM, Ahmad R, Cheng Y, Dutertre CA, Heinecke A, Rivino L, Tan A, Hansi NK, Zhang M, Xi S, Chong Y, Pflanz S, Newell EW, Kennedy PTF, Bertoletti A. 2020. Effects of hepatitis B surface antigen on virus-specific and global T cells in patients with chronic HBV infection. Gastroenterology 159:652-664

5. *Le Bert N, *Tan AT, Kunasegaran K, Tham CYL, Hafezi M, Chia A, Chng MHY, Lin M, Tan N, Linster M, Chia WN, Chen MI, Wang LF, Ooi EE, Kalimuddin S, Tambyah PA, Low JG, Tan YJ, Bertoletti A. 2020. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature 584:457-462

6. Le Bert N, Clamhan HE, Tan AT, Chia WN, Tham CYL, Lim JM, Kunasegaran K, Tan LWL, Dutertre CA, Shankar N, Lim JEM, Sun LJ, Zahari M, Tun ZM, Kumar V, Lim BL, Lim SH, Chia A, Tan YJ, Tambyah PA, Kalimuddin S, Lye D, Low JG, Wang LF, Wan WY, Hsu LY, *Bertoletti A, *Tam CC. 2021. Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection. Journal of Experimental Medicine 218(5):e20202617

 

OTHER PUBLICATIONS – RESEARCH ARTICLES

(Dr. Le Bert’s maiden name is Witt)

7. Witt N, Rodger G, Vandesompele J, Benes V, Zumla A, Rook GA, Huggett JF. 2009. An assessment of air as a source of DNA contamination encountered when performing PCR. Journal of Biomolecular Techniques (JBT) 20(4):236

8. Le Bert N, Chain BM, Rook, Noursadeghi M. 2011. DC priming by M. vaccae inhibits Th2 responses in contrast to specific TLR2 priming and is associated with selective activation of the CREB pathway. PLoS One 6(4):e18346

9. Lee SK, Chwee JY, Ma CA, Le Bert N, Huang CW, Gasser S. 2014. Synergistic Anticancer Effects of Pam3CSK4 and Ara-C on B-Cell Lymphoma Cells. Clinical Cancer Research 20(13):3485-95

10. *Lam AR, *Le Bert N, Ho SSW, Shen YJ, Tang MLF, Xiong GM, Croxford JL, Koo CXE, Ishii KJ, Akira S, Raulet DH, Gasser S. 2014. RAE1 ligands for the NKG2D receptor are regulated by STING-dependent DNA sensor pathways in lymphoma. Cancer Research 74:2193-2203

11. Koo CX, Kobiyama K, Shen YJ, Le Bert N, Ahmad S, Khatoo M, Aoshi T, Gasser S, Ishii KJ. 2015. RNA polymerase III regulates cytosolic RNA:DNA hybrids and intracellular microRNA expression. Journal of Biological Chemistry 290(12):7463-73

12. Shen YJ, Le Bert N, Chitre AA, Koo CXE, Nga XH, Ho SSW, Khatoo M, Tan NY, Ishii KJ, Gasser S. 2015. Genome derived cytosolic DNA mediates type I interferon-dependent rejection of B cell lymphoma cells. Cell Reports 11(3):460-473

13. Tan AT, Yang N, Krishnamoorthy TL, Oei V, Chua A, Zhao X, Tan HS, Chia A, Le Bert N, Low D, Tan HK, Kumar, Irani RFG, Ho ZZ, Zhang Q, Guccione E, Wai L-E, Koh, Hwang SW, Chow WC, Bertoletti A. 2019. Use of Expression Profiles of HBV-DNA Integrated into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy. Gastroenterology 156:1862-1876.e9

14. Bénéchet AP, De Simone G, Di Lucia P, Cilenti F, Barbiera G, Le Bert N, Fumagalli V, Lusito E, Moalli F, Bianchessi V, Andreata F, Zordan P, Bono E, Giustini L, Bonilla WV, Bleriot C, Kunasegaran K, Gonzalez Aseguinolaza G, Pinschewer DD, Kennedy PTF, Naldini L, Kuka M, Ginhoux F, Cantore A, Bertoletti A, Ostuni R, Guidotti L, Iannacone M. 2019. Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming. Nature 574:200-205

15. Tan-Garcia A*, Lai F*, Sheng Yeong JP, Irac SE, Ng PY, Msallam R, Tatt Lim JC, Wai LE, Tham CYL, Choo SP, Lim T, Young DY, D’Ambrosio R, Degasperi E, Perbellini R, Newell E, Le Bert N, Ginhoux F, Bertoletti A, Chen Q, Dutertre CA. 2020. Liver fibrosis and CD206(+) macrophage accumulation are suppressed by anti-GM-CSF therapy. JHEP Reports 2(1):100062

16. *Tan AT, *Linster M, Tan CW, Le Bert N, Chia WN, Kunasegaran K, Zhuang Y, Tham CYL, Chia A, Smith GJD, Young B, Kalimuddin S, Low JGH, Lye D, Wang LF, Bertoletti A. 2021. Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients. Cell Reports 34(6):108728

17. Chia WN*, Zhu F*, Ong SWX, Young, Fong BESW, Le Bert N, Tan CW, Tiu C, Zhang, Tan JSY, Pada S, Chan Y-H, Tham CYL, Kunasegaran K, MIC, Low JGH, Leo Y-S, Renia L, Bertoletti A, Ng LFP, Lye DC, Wang LF. 2021. Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study. The Lancet Microbe 2(5):e179

18. *Kalimuddin S, *Tham CYL, *Qui M, *de Alwis R, Sim JXY, Lim JME, Tan H-C, Syenina A, Zhang SL, Le Bert N, Tan AT, Leong YS, Yee JX, Ong EZ, Ooi EE, Bertoletti A, Low JG. 2021. Early T cell and binding antibody responses are associated with Covid-19 RNA vaccine efficacy onset. Med 2(6):682-688

19. Lozano-Ojalvo* D, Camara* C, Lopez-Granados E, Nozal P, a del Pino-Molina L, Bravo-Gallego LY, Paz-Artal E, Pion M, Correa-Rocha R, Ortiz A, Lopez-Hoyos M, Iribarren ME, Portoles J, Rojo-Portoles MP, Ojeda G, Cervera I, Gonzalez-Perez M, Bodega-Mayor I, Montes-Casado M, Portoles P, Perez-Olmeda M Oteo J, Sanchez-Tarjuelo R, Pothula V, Schwarz M, Brahmachary M, Tan AT, Le Bert N, Berin C, Bertoletti A, Guccione E*, Ochando J. 2021. Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID 19 recovered individuals. Cell Reports 34(6):108728

20. Tan AT, Lim JME, Le Bert N, Kunasegaran K, ChiaA, Qui M, Tan N, Chia WN, de Alwis R, Ying D, Sim JXY, Ooi EE, Wang LF, Chen MC, Young BE, Hsu LY, Low JGH, Lye DC, Bertoletti A. 2021. Rapid measurement of SARS-CoV-2 spike T cells in whole blood from vaccinated and naturally infected individuals. The Journal of Clinical Investigation 131(17):e152379

21. *Le Bert N, *Chia WN, *Wan WY, Teo AKJ, Chong SZR, Tan N, Tan DSC, Chia A, Tan IB, Kunasegaran K, Chua QX, Abdad MY, Ng ASH, Vasoo S, Ang JXL, Lee MS, Sun L, Fang J, Zhu F, Cook AR, Aw TC, Huang J, Tan C, Lee FS, Clapham H, Goh EJK, Peou MSS, Tan SP, Ong SK, Wang LF, *Bertoletti A, *Hsu LY, *Ong BC. 2021. Widely heterogeneous humoral and cellular immunity after mild SARS-CoV-2 infection in a homogeneous population of healthy young men: Heterogenous immunity to SARS-CoV-2. Emerging Microbes & Infections 10(1):2141-2150

22. Swadling L, Diniz MO, Schmidt NM, Amin OE, Chandran A, Shaw E, Pade C, Gibbons JM, Le Bert N, Tan AT, Jeffery-Smith A, Tan C, Tham CYL, Kucykowicz S, Aidoo-Micah G, J Rosenheim J, Davies J, Johnson M, Jensen MP, Joy G, McCoy LE, Valdes AM, Chain BM, Goldblatt D, Altmann DM, Boyton RJ, Manisty C, Treibel TA, Moon JC, van Dorp L, Balloux F, McKnight A, Noursadeghi M, Bertoletti A, Maini MK. 2021. Pre-existing polymerase specific T cells expand in abortive seronegative SARS-CoV-2. Nature 601(7891):110-117

23. Ma H, Lim TH, Leerapun A, Weltman M, Jia J, Lim YS, Tangkijvanich P, Sukeepaisarnjaroen W, Ji Y, Le Bert N, Li D, Zhang Y, Hamatake R, Tan N, Li C, Strasser SI, Ding H, Yoon JH, Stace NH, Ahmed T, Anderson DE, Yan L, Bertoletti A, Zhu Q, Yuen MF. 2021. Therapeutic vaccine BRII-179 restores HBV-specific immune responses inpatients with chronic HBV in a phase Ib/IIa study. JHEP Reports 3(6):100361

24. *Khoo NKH, *Lim JME, Gill US, de Alwis R, Tan N, Toh JZN, Ooi EE, Low JGH, Le Bert N, Kennedy PTF, Bertoletti A. 2022. Differential immunogenicity of homologous versus heterologous boost in Ad26.COV2.S vaccine recipients. Med in press

 

OTHER PUBLICATIONS – REVIEWS, REPLY, BOOK CHAPTER

1. Rook GA, Witt N. 2008. Probiotics and Other Organisms in Allergy and Autoimmune Diseases. Therapeutic Microbiology: Probiotics and Related Strategies 231-247

2. Lam AR, Chwee JY, Le Bert N, Sauer M, Pogge von Strandmann E, Gasser S. 2013. Regulation of self-ligands for activating natural killer cell receptors. Annals of Medicine 45:384-394

3. Le Bert N, Lam AR, Ho SS, Shen YJ, Liu MM, Gasser S. 2014. STING-dependent cytosolic DNA sensor pathways regulate NKG2D ligand expression. OncoImmunology, 3:e29259

4. Le Bert N, Gasser S. 2014. Advances in NKG2D ligand recognition and responses by NK cells. Immunology & Cell Biology, 92:230-236

5. Bertoletti A, Le Bert N. 2018. Immunotherapy for chronic hepatitis B virus infection. Gut and Liver 12(5):497

6. Bertoletti A, Le Bert N. 2019. Fine-Tuning TLR-7-Based Therapy for Functional HBV Cure. Hepatology Communications, 3:1289-1292

7. Bertoletti A, Tan AT, Le Bert N. 2021. The T-cell response to SARS-CoV-2: kinetic and quantitative aspects and the case for their protective role. Oxford Open Immunology iqab006

8. Bertoletti A, Le Bert N, Qui M, Tan AT. 2021. SARS-CoV-2-specific T cells in infection and vaccination. Cellular & Molecular Immunology, 18:2307-2312

9. Tan AT, Le Bert N, Bertoletti A. 2021. Difference in sensitivity between SARS-CoV-2–specific T cell assays in patients with underlying conditions. Reply. The Journal of Clinical Investigation, 131:e155701

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