Faridabad, Haryana, India
The HIV Vaccine Translational Research (HVTR) Laboratory was established in 2012 as a joint initiative between the Translational Health Science and Technology Institute (THSTI) — an autonomous body of the Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India — and IAVI. Closely linked with a global network of laboratories supported by IAVI, including the IAVI Neutralizing Antibody Center (NAC) for technical guidance, technology transfer support, global partner linkages, and trainings, the program is primarily focused on (a) studying the genetic and functional diversities of majorly circulating HIV-1 clade C in India (compared to the strain circulating in Africa) that will inform the selection of combinations of broadly neutralizing monoclonal antibodies (mAbs) as region-specific prevention products and (b) discovery and characterization of novel mAbs against HIV-1 and SARS-CoV-2, with particular reference to ones majorly circulating in India and globally.
THSTI and IAVI expanded their collaboration in 2019 to establish the Antibody Translational Research Program (ATRP). The objective of ATRP is to enable the discovery and translation of broadly neutralizing antibodies (bnAbs) for diseases of mutual concern to IAVI, THSTI and DBT that are affordable, applicable, and accessible to low- and middle-income countries (LMICs), and, subsequently, serve as a Center of Excellence (CoE) to help address the global burgeoning disease burden, in alignment with IAVI’s NAC and the Indian government’s efforts to create regional CoEs.
The ATRP — based at the NCR Biotech Science Cluster in Faridabad, in the National Capital Region of Delhi, India — comprises an interdisciplinary group of scientists from IAVI and THSTI with unique capabilities and multifaceted experience, which enable it to drive antibody research. The program focuses on setting up technologies, assays, and protocols, expanding relevant skill sets in the areas of antibody discovery, characterization, and translation, and promoting industry collaboration on promising prevention products against HIV and COVID-19. It also continues its efforts to establish strategic partnerships with leading academic and industry partners in India and across the globe, with a special emphasis on building capacity and facilitating indigenous scientific innovation in and between LMICs. IAVI’s NAC continues to work collaboratively with scientists at the ATRP to develop innovative tools, technologies, and avenues of collaboration that could be of significant benefit for advancing the development of solutions for a wide range of global health threats, including tuberculosis (TB), neglected tropical diseases (NTDs) and emerging infectious diseases (EIDs).
Globally, multiple products (antibodies and vaccines) and novel delivery systems have entered early phase trials for diseases of concern for LMICs, e.g., HIV vaccines and HIV bnAbs. However, given the diversity of the virus, it is imperative to have products that are suitable against circulating strains. The ATRP leverages the platform established to assess the suitability of immunogens and antibodies that will be appropriate for both India and Africa. Further, given India’s manufacturing prowess, these immunogens can be indigenously manufactured and tested in clinical trials for potential introduction in the country.
Below are some of the achievements brought to the fore by the ATRP and the innovative global and national partnerships it has fostered through the years.
In 2021, the ATRP successfully isolated two novel COVID-19 monoclonal antibodies, making it the first in India (and an LMIC) to do so. This has been taken into manufacturing in collaboration with an Indian industrial partner for product development. The ATRP currently also has two projects at the proof-of-concept stage, including the isolation and identification of two novel HIV mAbs from within India, and the design and patenting of fully cleaved envelope trimers as immunogens.
Technologies and platforms
The ATRP has established 13 technology platforms in India for HIV & COVID-19 antibody and HIV vaccine research, including peripheral blood mononuclear cell isolation, cryopreservation, thawing and transportation for B-cell biology studies, sanger sequencing for HIV virus profiling, and flow cytometer-based technology for antigen-specific single memory B cells sorting, among others.
The ATRP has filed four Indian patents — COVID-19 Antibody (2021), Engineered HIV-1 Envelope Immunogen (2019), Engineered Recombinant Protein Antigen (2017), and Isolated Nucleotide Sequence for the Prevention of HIV-1 Infection (2016). It has also been awarded two international patents for its discovery of HIV-1 Clade C Envelope Glycoproteins (2016) and a Trimeric Envelope Immunogen (2016).
The team has published over 20 publications in high-impact journals.
The investigators at the program are as follows:
- Jayanta Bhattacharya, director, IAVI, and principal investigator, THSTI
- Suprit Deshpande, scientific project manager, THSTI
- Ranajoy Mullick, senior scientist, IAVI
- Sohini Mukherjee, senior specialist, IAVI
- Jyoti Sutar, specialist, IAVI
- Priyanka Jayal, research associate, THSTI
- Mohammad Yousuf Ansari, research associate, THSTI
Scientific project management:
Selected publications by ATRP investigators and their collaborators:
Potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against SARS-CoV-2 Delta. PLOS Pathogens Apr 28;18(4): e1010465. 2022. (Open access)
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 Infect Dis. (Apr;22(4): 473-482. 2022. (Open access)
Long-term Durable Humoral Immune Response to Heterologous Antigenic Exposure Post six months by Natural SARS-CoV-2 Infection and Vaccination. medRxiv. doi: https://doi.org/10.1101/2022.02.23.22271381. 2022. (Open access)
Neutralization diversity of HIV-1 Indian subtype C envelopes obtained from cross sectional and followed up individuals against broadly neutralizing monoclonal antibodies having distinct gp120 specificities. Retrovirology 18: 12. 2021. (Open access)
Geospatial HIV-1 subtype C gp120 sequence diversity and its predicted impact on broadly neutralizing antibody sensitivity. PLoS ONE. 16(5): e0251969. 2021. (Open access)
Elicitation of potent serum neutralizing antibody responses in rabbits by immunization with an HIV-1 clade C trimeric Env derived from an Indian elite neutralizer. PLOS Pathogens 17 (4): e1008977. 2021. (Open access)
Effect of diversity in gp41 membrane proximal external region of primary HIV-1 Indian subtype C sequences on interaction with broadly neutralizing antibodies 4E10 and 10E8. Virus Res. 273: 197763. 2019. (Subscription required)
The chaperone ERp29 is required for tunneling nanotube formation by stabilizing. MSec. J Biol. Chem. May 3;294(18):7177-7193. 2019. (Subscription required)
Characterization of the membrane-bound form of the chimeric, B/C recombinant HIV-1 Env, LT5.J4b12C. J Gen. Virol 99 (10): 1438-1443. 2018. (Open access)
Broad neutralization response in a subset of HIV-1 subtype C-infected viraemic non-progressors from southern India. J Gen Virol. 2018 Mar;99(3):379-392. (Open access)
Envelope proteins of two HIV-1 clades induced different epitope-specific antibody response. Vaccine. 2018 Mar 14;36(12):1627-1636. 2018. (Subscription required)
Cell surface ectodomain integrity of a subset of functional HIV-1 envelopes is dependent on a conserved hydrophilic domain containing region in their C-terminal tail. Retrovirology. 2018 Jul 20;15(1):50. 2018. (Open Access)
Characterization of a stable HIV-1 B/C recombinant, soluble and trimeric envelope glycoprotein (Env) highly resistant to CD4-induced conformational changes. Journal of Biological Chemistry. 292 (38): 15849-15858. 2017. (Open Access)
Stabilization of a soluble, native-like trimeric form of an efficiently cleaved Indian HIV-1 clade C envelope glycoprotein. J Biol Chem. 292(20):8236-8243. 2017. (Open Access)
Dual immunity concomitantly suppresses HIV-1 progression. Trends in Microbiol. 25 (5): 334-335. 2017. (Subscription required)
Association of mutations in V3/C3 domain with enhanced sensitivity of HIV-1 clade C primary envelopes to autologous broadly neutralizing plasma antibodies. Retrovirology 13: 41. 2016. (Open Access)
HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms. Retrovirology 30;13(1):60. 2016. (Open Access)
Conformational Epitope-Specific Broadly Neutralizing Plasma Antibodies Obtained from an HIV-1 Clade C Infected Elite Neutralizer Mediate Autologous Virus Escape through Novel Mutations in V1 Loop. Journal of Virology 90 (7): 3446-3457. 2016. (Open Access)
Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an HIV-1 Infected Indian Individual. PLOS One; 2015 May 11;10(5): e0125575. 2015. (Open Access)
An efficiently cleaved HIV-1 clade C Env selectively binds to neutralizing antibodies. PLOS One; 2015 Mar 30;10(3): e0122443. 2015. (Open Access)
Determinants in V2C2 region of HIV-1 clade C primary envelopes conferred altered neutralization susceptibilities to IgG1b12 and PG9 monoclonal antibodies in context dependent manner. Virology 462-463: 266–272. 2014. (Subscription required)