निमेश गुप्ता
Research Interest:
Summary of Research:Our research focuses on understanding how the immune system mounts strong and lasting antibody responses to viruses. We investigate T cell–B cell interactions, with a particular emphasis on follicular helper T (Tfh) cells that drive germinal center formation and high-quality humoral immunity. By defining the unique traits and functional signatures of Tfh cells, we aim to uncover the immune mechanisms essential for broad and durable protection. The global aim is to identify and harness the positive attributes of Tfh cells for the rational design of vaccines.
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Our laboratory works at the interface of fundamental and translational immunology, with a core focus on understanding the biology of follicular helper T (Tfh) cells—a specialized subset of CD4+ T cells essential for supporting B cell function and driving germinal center–derived antibody responses. Despite two decades of progress, the precise cues that generate potent Tfh cells capable of inducing long-term, broadly protective humoral immunity remain incompletely understood. Understanding these signals is crucial for designing next-generation vaccines. We study this through two main models:
Human Vaccination - We investigate how robust and durable humoral immunity is shaped in humans following infection or vaccination, focusing on mosquito-borne viruses such as Japanese encephalitis, as well as SARS-CoV-2. By leveraging longitudinal cohorts of human vaccination and natural infection, we compare the diversity, characteristics, and function of Tfh cells triggered by vaccines versus natural infection.
Virus infection – Our dengue program explores immune responses linked to disease severity and protection. We discovered a novel IL-21+ T-cell subset in the extrafollicular niche that plays a critical role in exacerbating severe dengue by driving dysregulated antibody responses. Studying this alongside traditional Tfh cells opens new avenues for targeted therapies and safer vaccine designs, addressing challenges like Antibody-Dependent Enhancement (ADE).
Our research integrates viral immunology, deep immune phenotyping, single-cell genomics (10X Genomics), metabolomics, and ex vivo assays. We also use murine models to validate mechanistic insights from human studies. This multidisciplinary framework allows us to define Tfh signatures that correlate with long-lasting and broadly protective antibody responses. We are also interested in using this knowledge to develop T-cell based vaccines for Dengue and Japanese encephalitis.
Through this program, we are building a unique national platform for dissecting human T–B cell interactions in infection and vaccination, with direct applications in vaccine innovation and pandemic preparedness.
Group Members:
Bhushan Nikam, Someshwar Nath Jha, Suvechchha Pandit, Bhavya Ahuja, Vivekananda Barik, Shayon Mahalanobis, Samiya Bashir (PhD Scholars); Md. Umar Saad (Project Scientist); Prajwal Roopnath (Project staff); Sudipta Das, Inderjit Singh (Technical officers)
Bhushan Nikam, Someshwar Nath Jha, Suvechchha Pandit, Bhavya Ahuja, Vivekananda Barik, Shayon Mahalanobis, Samiya Bashir (PhD Scholars); Md. Umar Saad (Project Scientist); Prajwal Roopnath (Project staff); Sudipta Das, Inderjit Singh (Technical officers)
Awards:
• 2025: Global Health Travel Award of Bill and Melinda Gates Foundation for Keystone Symposia on Vaccinology to be held at Washington, DC, USA.
• 2023: Healthcare Changemaker Awards conferred at ‘Healthcare Changemakers Conclave-2023’ for contribution to the healthcare landscape in India.
• 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).
Indian Council of Medical Research
Patents:
1. WO2017/012959 (USA, Europe and Japan): Methods and pharmaceutical compositions for inducing immune tolerance by mucosal vaccination with Fc-coupled antigens.
2. US62/188,004: Prenatal therapy to induce immune tolerance.
3. 202111003148 (India): A novel method to evaluate the quality of antigen-specific T cells in infection and vaccination.
4. 202211046391 (India): A dengue virus follicular T helper (Tfh) cell specific peptide megapool and its use thereof.
5. 202411072617 (India): A robust huh7.vil stable cell line overexpressing ACE2 and TMPRSS2 and implementations thereof
Publications:
- Asgar Ansari, Shilpa Sachan, Jatin Ahuja, Sureshkumar Venkadesan, Bhushan Nikam, Vinod Kumar, Shweta Jain, Bhanu Pratap Singh, Poonam Coshic, Kapil Sikka, Naveet Wig, Alessandro Sette, Daniela Weiskopf, Debasisa Mohanty, Manish Soneja and Nimesh Gupta*. 2025. Distinct features of a peripheral T helper subset that drives the B cell response in dengue virus infection. Cell Reports, 44, 115366. https://doi.org/10.1016/j.celrep.2025.115366. (Featured in Editor’s Choice Section - Science Immunology - DOI: 10.1126/sciimmunol.ady4137)
- Jitender Jitender, Bhusarapu Vikram Kumar, Sneha Singh, Geetika Verma, Reetesh Kumar, Pranaya Manjari Mishra, Sahil Kumar, Santhosh K. Nagaraj, Joydeep Nag, Christy Margrat Joy, Bhushan Nikam, Dharmendra Singh, Pooja Pooja, Nidhi Kalidas, Shubham Singh, Mumtaz Saheb, Ashwani Kumar Bhardwaj, Dhananjay Singh Mankotia, Rajesh P. Ringe, Nimesh Gupta, Shashank Tripathi and Ravi Mishra. 2024. Mammalian cell expressed prefusion-stabilized trimeric spike protein is a potent vaccine antigen and confers near-complete protection against SARS-CoV-2 infection in preclinical model. Vaccine Aug 13;42(20):126099. doi: 10.1016/j.vaccine.2024.06.066.
- Asgar Ansari, Poonam Coshic, Ashok Sharma, Alessandro Sette, Daniela Weiskopf, and Nimesh Gupta*. 2024. T-B coculture assay for functional analysis of antigen-specific memory CD4+ T cells. STAR Protocol 5 (2) 103119 Article
- Rajesh Vikkurthi, Asgar Ansari, Anupama R Pai, Someshwar Nath Jha, Shilpa Sachan, Suvechchha Pandit, Bhushan Nikam, Anurag Kalia, Bimal Prasad Jit, Hilal Ahmad Parray, Savita Singh, Pallavi Kshetrapal, Nitya Wadhwa, Tripti Shrivastava, Poonam Coshic, Suresh Kumar, Pragya Sharma, Nandini Sharma, Juhi Taneja, Anil K Pandey, Ashok Sharma, Ramachandran Thiruvengadam, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Shinjini Bhatnagar and Nimesh Gupta*. 2022. Inactivated virus vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern. Nature Microbiology 7: 974-985. (https://doi.org/10.1038/s41564-022-01161-5)
- Sneha Singh, Bhusarapu Vikram Kumar, Jitender Jitender, Pranaya Manjari Mishra, Geetika Verma, Sahil Kumat, Suvechchha Pandit, Reetesh Kumar, Rajesh P. Ringe, Shashank Tripathi, Nimesh Gupta and Ravi Mishra. 2024. Scalable bioprocess for the high-level expression and purification of recombinant trimeric SARS-CoV-2 spike ectodomain-based immunogen (IMT-CVAX). Process Biochemistry, 332-346.
- 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, 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.
