The HIV Vaccine Translational Research (HVTR) Laboratory at the Translational Health Science & Technology Institute (THSTI), NCR Biotech Science Cluster, Faridabad is the country’s premier research laboratory dedicated to HIV vaccine research and development, which was established recognizing the need for research and clinical trial capability that will addresses the particular needs of the Indian population and the strains of HIV that predominate in India. The HVTR laboratory carries out early translational research and development under the joint partnership program between THSTI and the International AIDS Vaccine Initiative (IAVI) that follows the principles of a center of excellence with unique strengths towards accelerating the efforts towards discovery through development of broadly neutralizing antibodies (bnAbs) to HIV-1, and characterizing antigenic properties of HIV-1 envelope proteins (Env) for their suitability in informing immunogen design. The HVTR laboratory at the THSTI is comprised of interdisciplinary team of scientists, which with a breadth of experience in virology, protein design and engineering, alongside neutralizing antibody discovery and their characterization at the molecular level has been addressing its research goals through partnering with other laboratories and clinical research centers both globally and locally. The HVTR laboratory employs different approaches to drive research in antigen and antibody discovery with overall goal in early translation of product discovery through pre-clinical development via strategic and complementary partners with academia, clinics, hospital and industries both locally and globally.
R&D goals of the HVTR Laboratory at THSTI
HIV-1 uses its envelope protein (Env) which is present on its outer surface to bind to CD4 for virus entry and establish infection. A key strategy of HIV-1 vaccine design is to identify immunogens that can elicit broadly neutralizing antibodies (bnAbs). Since, HIV-1 Env is the sole target of neutralizing antibodies, the focus of the HVTR has been to identify Env sequences, with particular reference to the predominantly circulating subtype (usually subtype C) that display near native conformation with favorable antigenic properties. The scientists at the HVTR laboratory have identified HIV-1 Envs (which have been isolated from Indian patients) that possess desired antigenic properties to be considered for immunogen design. In addition, the laboratory has been working to identify HIV+ individuals who naturally produced broadly neutralizing antibodies by screening of serum samples from a large number of slow progressing patients. Under Protocol G project, with close collaboration with the IAVI-led Neutralizing Antibody Center (NAC) and our clinical partner at the YRGCARE in Chennai, scientists at the HVTR laboratory by screening 200 patients, identified eleven individuals who sera showed evidence of neutralization breadth with 60-90% breadth on a large cross-clade global isolate panel. Using a battery of approaches, the investigators at THSTI identified the epitopes that are potentially being targeted by top three antibodies. This information is currently being used to design antigen baits to enrich for the antibodies of interest through antigen-specific single memory B cell sorting and antibody cloning.
To prepare for prompt global access to affordable antibodies, the HVTR laboratory strives to promote its capacity in the space of Antibody Translational Research and is building strategic and complementary public-private partnerships to enable the discovery and development of accessible, affordable monoclonal antibodies through product optimization, low-cost manufacturing, and new policy frameworks and business models. The vision of the laboratory is to establish as a local antibody discovery and development group in India that will leverage Indian donor samples to isolate highly potent antibodies that will become effective and affordable interventions for diseases that have high burdens in India and globally. It is also working to establish itself to be able to perform in depth and affordable developability assays to screen antibody candidates to identify leads for manufacturing. Additionally, the laboratory will setup the ability to perform preclinical therapeutic or prevention efficacy studies in different animal models, including mice and non-human primates.