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निमेश गुप्ता

Research Interest:

Our group works in the area of virus immunology. The goal is to identify the determinants of long-lasting protective humoral immunity. Major emphasis is on understanding the biology and traits of CD4+ follicular T helper (Tfh) cells that are indispensable for the generation of germinal center derived humoral immunity. The long-term goal is to identify and harness the positive attributes of Tfh cells for rational designing of vaccines.

Summary of Research:

Our lab works at the interface of fundamental and translational immunology. Tfh cells are a specialized subset of CD4+ T cells that provide help to B cells and devise the magnitude and quality of germinal-center derived antibodies. In the last two decades, the factors that govern Tfh cells differentiation and the unique role of Tfh cells in the establishment of humoral immunity have been extensively studied. However, more needs to be learned about the cues that lead to the generation of potent Tfh cells in long-lasting and broadly protective humoral immunity. Certainly, this knowledge will be phenomenal for vaccine development. Therefore, our attempts are focused on resolving the traits and function of Tfh cells in long-term sustained immunity. We study Tfh cells in the settings of immunological memory acquired after virus infection or human vaccination. We are integrating viral immunology, deep immunophenotyping, single-cell genomics, and metabolomics approaches to investigate the biology of Tfh cells in two different models - (i) Human vaccination. Here, we are studying the characteristics and clonotypic diversity of human Tfh cells established in response to licensed human vaccines like SA14-14-2 Japanese encephalitis (JE) vaccine, SARS-CoV-2 vaccines etc. To identify the ideal attributes of Tfh cells in long-term immunity, we are studying the function and traits of Tfh cells induced in vaccination to that of natural infection. To do this, we have established longitudinal cohorts of controlled vaccination and virus infection. Besides, we are also using ex vivo Tfh model and mouse models to mechanistically investigate the leads generated from our human studies. (ii) Human virus infection. In this program, our attempts are focused on providing insight into the immunological memory and T-cell determinants of humoral responses to viruses like Dengue virus. Here, we are exploring the biology of Tfh cells and related CD4+ T-cell subsets at a greater depth in patients with diverse outcomes of virus infection.

Group Members:
Asgar Ansari, Bhushan Nikam, Someshwar Nath Jha, Suvechchha Pandit, Bhanu Pratap Singh (PhD scholars); Sathi Mallick (Postdoctoral fellows); Yatish Thakarey, Asha Kushwaha (Project staff); Sudipta Das, Inderjit Singh (Technical officers)

Awards:
• 2022: ​Mid-Career Immunologist Oration Award by the Indian Immunology Society for the contribution in the area of “T cell immunity to vaccines”
• 2021: Young Scientist award, India International Science Festival-2020
• 2020: Early Career Faculty Award by American Association of Immunology
• 2019: The Merieux Foundation Fellowship for the Advancement in Vaccinology
• 2016: Martin Villar Award
• 2016: Ramalingaswami Fellowship
• 2016: Global Health Travel Award of Bill and Melinda Gates Foundation
• 2013: European Federation of Immunological Societies Young Investigator Award
• 2013: International Society of Thrombosis & Haemostasis Young Investigator Award
• 2008: Raman-Charpak Fellowship, Institute Pasteur, Paris, France
• 2008-2010: Brig. K.M. Rao Award, Defence R&D Establishment, India

Funding:
Department of Biotechnology, Department of Science and Technology (SERB), NER-BPMC Twinning Program (DBT), Ramalingaswami Fellowship, Indo-USA Human Immunophenotyping Consortium, National Biopharma Mission Dengue Consortium (BIRAC), National Biopharma Mission COVID-19 Consortium (DBT-BIRAC), Intensification of Research in High Priority Areas (DST).

Patents:
• 202211046391 (Indian Patent): A dengue virus follicular T helper (Tfh) cell specific peptide megapool and its use thereof.
• WO2017/012959: Methods and pharmaceutical compositions for inducing immune tolerance by mucosal vaccination with Fc-coupled antigens.
• US62/188,004: Prenatal therapy to induce immune tolerance.
• 202111003148 (Indian Patent) - A novel method to evaluate the quality of antigen-specific T cells in infection and vaccination.

Publications:
  • Vikkurthi, R., Ansari, A., Pai, A.R…. Grifoni, A, Weiskopf, D, Sette, A, Bhatnagar, S and Gupta, Nimesh*. Inactivated whole-virion vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern. Nature Microbiology (2022). https://doi.org/10.1038/s41564-022-01161-5
  • Asgar Ansari, Shilpa Sachan, Bimal Prasad Jit, Ashok Sharma, Poonam Coshic, Alessandro Sette, Daniela Weiskopf and Nimesh Gupta*, An efficient immunoassay for the B cell help function of SARS-CoV-2-specific memory CD4+ T cells, Cell Reports Methods (2022), https://doi.org/10.1016/j.crmeth.2022.100224
  • Thiruvengadam R, Awasthi A, Medigeshi G, Bhattacharya S, Mani S, ….., Gupta Nimesh, Pandey AK, Bhattacharya J, Agrawal A, Vrati S, Bhatnagar S, Garg PK (2022) Effectiveness of ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 infection during the delta (B.1.617.2) variant surge in India: a test-negative, case-control study and a mechanistic study of post-vaccination immune responses. Lancet Infectious Diseases 22(4):473-482.
  • Asgar Ansari, Rakesh Arya, Shilpa Sachan, Someshwar Nath Jha, Anurag Kalia, Anupam Lall, Alessandro Sette, Alba Grifoni, Daniela Weiskopf, Poonam Coshic, Ashok Sharma, and Nimesh Gupta* (2021) Immune memory in mild COVID-19 patients and unexposed donors reveals persistent T cell responses after SARS-CoV-2 infection. Frontiers in Immunology 12:636768.
  • Alain Townsend, Pramila Rijal, Julie Xiao, Tiong Kit Tan, Kuan-Ying A Huang, Lisa Schimanski, Jiangdong Huo, Nimesh Gupta, ….. Etienne Joly (2021) A haemagglutination test for rapid detection of antibodies to SARS-CoV-2. Nature Communication, 12, 1951. https://doi.org/10.1038/s41467-021-22045-y
  • Chauhan S, Rathore DK, Sachan S, Desmazes SL, Gupta Nimesh, Awasthi A, Vrati S, and Kalia M (2021) Japanese encephalitis virus infected human monocyte-derived dendritic cells activate a transcriptional network leading to an antiviral inflammatory response. Frontiers in Immunology 12:638694.
  • Anurag Kalia, Mona Agrawal and Nimesh Gupta (2020) CD8+ T cells are crucial for humoral immunity establishment by SA14-14-2 live attenuated Japanese encephalitis vaccine. European Journal of Immunology. 10.1002/eji.202048745.
  • Gupta N, Culina S, Meslier Y, Dimitrov J, Delignat S, Gangadharan B, Lecerf M, Justesen S, Salomon B, Scott DW, Kaveri SV, Mallone R, Lacroix-Desmazes S (2015) Prevention of immune responses to antigens and protein therapeutics by transplacental induction of central and peripheral T-cell tolerance. Science Trans Med. 7: 275ra21.
  • Gupta N*, Wispelaere M, Lecerf M, Kalia M, Scheel T, Vrati S, Berek C, Kaveri S, Despres P, Lacroix-Desmazes S, Dimitrov J (2015) Neutralization of Japanese Encephalitis Virus by heme induced broadly reactive human monoclonal antibody. Scientific Reports. 5, 16248. *Corresponding Author
  • Culina S, Gupta N, Boisgard R, Afonso G, Gagnerault MC, Dimitrov J, Østerbye T, Justesen S, Luce S, Attias M, Kyewski B, Buus S, Wong FS, Lacroix-Desmazes S, Mallone R (2015) Materno-fetal transfer of preproinsulin through the neonatal Fc receptor prevents autoimmune diabetes. Diabetes. pii: db150024
  • Gupta N, Hegde P, Lecerf M, Nain M, Kalia M, Vrati S, Bayry J, Lacroix-Desmazes S, Kaveri S (2014) Japanese encephalitis virus expands regulatory T cells by increasing the expression of PD-L1 on dendritic cells. Eur J Immunol. 44:1363-1374.
  • Gupta N, Legoff J, Chamat S, Mercier-Delarue S, Touzelet O, Power UF, Kazatchkine MD, Simon F, Lacroix-Desmazes S, Bayry J, Kaveri S (2013) Affinity-purified Respiratory Syncytial virus antibodies from intravenous immunoglobulin exert potent antibody-dependent cellular cytotoxicity. PLoS ONE. 8(7): e69390.
  • Gupta N and Lakshmana Rao PV (2011) Transcriptomic profile of host response in Japanese encephalitis virus infection. Virol J. 8:92.
  • Gupta N, Bhaskar AS, and Lakshmana Rao PV (2011) Transcriptional regulation and activation of the mitogen-activated protein kinase pathway after Japanese encephalitis virus infection in neuroblastoma cells. FEMS Immunol Med Microbiol. 62:110-121.
  • Gupta N, Lomash V, and Lakshmana Rao PV (2010) Expression profile of Japanese encephalitis virus induced neuroinflammation and its implication in disease severity. J Clin Virol. 49:4-10.

Faculties

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