Infectious Disease Biology

Despite India’s rapid economic growth and growing technological prowess, it continues to face a heavy burden of infectious diseases, including high rates of HIV/AIDS, tuberculosis, malaria, and other neglected diseases. Towards this direction with the vision to mitigate the problems associated with these diseases, the Department under Infectious Disease Biology Program solicits a wide array of projects on bacterial, viral, parasitic, and fungal diseases spanning the spectrum from basic biology of human pathogens and their interaction with human hosts, through translational and clinical research toward the development of new and improved diagnostics, drugs, and vaccines for infectious diseases.The following priorities have been envisaged for this program:

  • Understanding the molecular structure and function of known viral, bacterial, fungal and parasitic pathogens and identify new pathogens.
  • Extending insights into mechanisms of infection, pathogenicity, virulence, host-pathogen interactions, development of drug resistance for diseases such as TB, repurposing of drugs for infectious diseases and anti-microbial resistance.
  • Development of indigenous, reliable, rapid, sensitive, specific, cost-effective, and easy to use in a variety of settings diagnostic platforms and technologies.
  • Conducting research to better understand and enhance immune responses, and to identify promising new vaccine targets for infectious diseases of national as well as global health importance.
  • Identifying potential targets for developing novel approaches to broad-spectrum interventions and new strategies for developing immunotherapies, including those based on host responses.

Ongoing Activities:

  1. Bacterial disease:
  2. Under the aegis of this program various R&D efforts have been supported in the area of bacterial diseases such as Mycobacterium tuberculosis, Pseudomonas aeruginosa, Acinetobacterbaumannii, Salmonella sp., Staphylococcus sp., Helicobacter pyloi, Shigellosis, Trichomonasvaginalis, Meningitis, Urinary tract infection, etc.However, considering the huge disease burden of TB in our country, the major emphasis is being given on the support on technological interventions in terms of diagnostics, therapeutics and vaccines in the area of TB. Major activities are as follows:

    1. Tuberculosis (TB):Basic studies on various diagnostic markers for Mycobacteriumtuberculosis including MDR, XDR, ocular, extra-pulmonary TB and TB with other co-morbidities like HIV, meningitis etc., have been supported. The development of point-of-care diagnostic assays, aptamer-based diagnostic toolbox and other antibody based diagnostic assays have also been successfully implemented and further considered for proper handholding for validation and commercialization process. Other studies like identification of therapeutic leads, molecular mechanism of pathogenesis, host-pathogen interactions, immunological studies and emergence of drug resistance mechanism are also the routine efforts under this program.
    2. Antimicrobial Resistance (AMR): Various basic studies on evolution of drug resistance mechanism in bacterial pathogens like Acinetobacterbaumannii, Pseudomonas aeruginosa, ESKAPE Pathogens, identification of therapeutic interventions for combating AMR etc, are being routinely supported under this program. 
  3. Viral Diseases:
  4. The program fosters conducting and supporting research for basic disease biology, molecular mechanism of pathogenesis, host-pathogen interactions of viral infections like HIV, Dengue, Chikungunya, influenza, Hepatitis C, Hepatitis B etc. Biomedical research supported under this program provides the tools necessary to develop diagnostic tests, new and improved treatments, vaccines, and other means to combat these threats. This includes working toward HIV cohort studies, dengue diagnostics and vaccine, chikungunya diagnostics that could provide long-lasting protection against these viral threats. Major activities in this category are as follows:

    1. Cohorts for HIV Resistance and Progression in Indian Children and Adults (CoHRPICA):

      Under DBT-ICMR collaborative effort on HIV/AIDS, a consortia based Cohorts for HIV Resistance and Progression in Indian Children and Adults (CoHRPICA) Program was initiated in 2017-18 with the aim to create uniform standardized cohorts across stages of HIV-infection, the first centralized state-of-the-art bio-repository at National AIDS Research Institute (NARI), Pune for access to biological samples and a National Database at National Institute of Epidemiology (NIE), Chennai to aid in identification of critical research questions and promoting multidisciplinary research collaborations to address the national HIV epidemic. While all sites have been engaged in community engagement activities in alignment with their respective community engagement plans, NARI has developed a preliminary set of experiential learning tools working with community leaders. These tools bring together ideas from behavioural sciences, social psychology, gamification, participatory theatre and the creative arts and are currently focused on educating the communities about HIV and need for biomedical research to help the communities make an informed decision on participation.
    2. Indo-South Africa Collaborative Program on HIV/TB: DBT in collaboration with DST, and Medical Research Council & Dept. of Science & Technology, Govt. of South Africa embarked on a collaborative Research Program on HIV, TB and TB/HIV. This collaborative program is under the framework of bilateral Science & Technology Cooperation agreement between the Department of Science & Technology, Ministry of Science & Technology, Governments of India and South Africa. Three joint proposals in TB, HIV, TB/HIV have been recommended under this collaborative effort.    Scientists from THSTI, Faridabad have developed a new soluble native-like Envtrimer, isolated from an elite neutralizer in India, for single B cell sorting and isolation of broadly neutralizing antibodies. A patent “Engineered HIV-1 Envelope Immunogen” has been filed. In the same project, AIIMS has isolated 2 broadly neutralizing antibodies from a paediatric elite neutralizer in India which are being characterized for their breadth and potency at THSTI. In a parallel effort, THSTI is also evaluating cross-neutralization potential of CAP256.VRC26 antibody, isolated in South Africa, to assess its suitability against Indian subtype C.
    3. Indo-Dutch Program on HIV:The Indo-Dutch Collaborative Program on HIV/AIDS focused on “Understanding disease dynamics towards effective management of prevention and treatment of HIV/AIDS” aims to bring together an interdisciplinary team of scientists from Centers of Excellence across India and Netherlands to accelerate development of new tools and interventions for effective HIV disease management. This program was officially launched in May 2018 and preparatory activities were initiated towards effective implementation of the program objectives. However, given the introduction of ‘Test and Treat’ in India, n scientific objectives were revised.
    4. Dengue: Dengue virus genome (RNA) codes for a polypeptide which harbours total ten proteins among which three are the structural proteins (Capsid, Envelop and Pre-membrane) and the seven are the non-structural proteins (NS1, NS2A, NS2B NS3, NS4A, NS4B and NS5). Scientist from University of Hyderabad developed a novel anti- NS2BNS3pro antibody based indirect ELISA test for the diagnosis of dengue virus infections.
  5. Parasitic diseases:
  6. Parasites are being increasingly recognized as important pathogens with significant global economic, environmental, and public health impacts. More than three billion people worldwide are infected with one or more parasites with varying morbidity and mortality. India carries 4% of the global malaria burden and contributes 87% of the total malaria cases in South-East Asia.The overriding goals of this program are as follows:

    1. To gain insight into the clinical syndromes associated with parasitic infections
    2. To understand and help define the pathogenesis underlying clinical disease
    3. To develop better diagnostic tools for the species-specific diagnosis of active parasitic infection
    4. To identify better therapeutic interventions for the control of these infections
    5. To support vector-control program

    Major Areas of Research

    Malaria:

    Many Centre of Excellencehave been supported in the area of Malaria. Some of the basic interventions supported under these CoEs are as follows:

    1. Molecular Machinery of Plasmodium: Signaling, Autophagy and Ubiquitin Proteasome System (UPS)
    2. Molecular dissection and inhibitor discovery against motors associated with protein translation in malaria parasites
    3. Malarial Parasite Biology: An avenue to discover new drug targets
    4. Programme Support on Molecular Parasitology
    5. Programme support on understanding critical events in biology of blood stage of malaria parasites

    Leishmania:

    R&D efforts to understand the mechanism of pathogenesis, identification of drug targets for the control of Lieshmaniasis have been implemented under this program.

  7. Fungal Diseases:
  8. Fungal diseases are caused by a wide variety of fungi that are commonly found in the environment. Invasive fungal infections rarely occur in healthy people, but fungi can cause serious infections in individuals with weakened immune systems.Fungal diseases are a growing threat to human health. While healthy people rarely suffer from serious fungal infections, people living with HIV/AIDS, cancer patients, organ and stem cell transplant patients, and hospitalized patients are vulnerable to infection. There are only four classes of antifungal drugs, and fungal strains resistant to these drugs are emerging. The Department is conducting and supporting basic research under this program to understand how fungal pathogens cause disease and how the immune system responds to infection. It is also conducting and supporting the science to find new ways to diagnose, treat and prevent fungal infections. Major focus is in the area of Candida albicancs based diseases and drug resistant fungal infections..

    Major initiatives launched:

    1. Repurposing of drugs: In order to discover economically viable new treatments against various diseases, the Department recently through a specific call on “Repurposing of Drugs” has supported R&D projects in disease areas covering Japanese encephalitis, chikangunya, dengue, malaria, visceral leishmaniasis and antimicrobial resistance. 
    2. Mission Antimicrobial Resistance (AMR):

      Considering Antimicrobial Resistance as global threat, during 2018-2019 FY, the Department has launched an ambitious “Mission program on Antimicrobial Resistance” with the vision to develop indigenous and cost-effective therapies against AMR; categorization of AMR-specific pathogen priority list of India; establishment of Bio-repository for AMR-specific pathogens; and development of rapid and cost-effective diagnostic kits to identify AMR-specific pathogens.

    Considering AMR as the top most national priority, the Department has notified National Centre for Microbial Resource (NCMR), National Centre of Cell Sciences, Pune (an Autonomous Institute of DBT) to function as a Bio-repository for resistant microbes/infective agents (Bacteria and Fungi)” and to carry out collection, storage, maintenance, preservation and characterization of these microbes across the country. After deliberating several consultations meeting with various pertinent stakeholders, NCMR has developed uniform SOPs for deposition, storages and transport of AMR samples.

    Recently, NCMR has been selected as State reference laboratory under Maharashtra State Antimicrobial Resistance (MAHASAR) surveillance network program of Maharashtra in collaboration with WHO. Food Safety and Standards Authority of India (FSSAI) has notified it’s all 163 laboratories and 19 referral food testing laboratories across the country to deposit their AMR-specific samples to NCMR Bio-repository, Pune. Further, DRDO and NCDC have also notified their laboratories to deposit their samples at NCMR, Pune. 

    Further, the Department is working with WHO, Country Office, New Delhi to share the information regarding National AMR-specific Pathogen priority list which will be available very soon. The Department in collaboration with BIRAC, New Delhi is preparing a landscaping report on existing rapid and cost-effective diagnostic kits to identify AMR-specific pathogens, which will be useful to focus on supporting R&D efforts in developing AMR specific rapid and cost effective diagnostic kits.

    In a process to fulfil the ambition of this program, Department of Biotechnology (DBT) in collaboration with Biotechnology Industry Research Assistance Council (BIRAC) has announced support for Projects in the area of development of new antibiotics and alternatives to antibiotics to counter AMR. Under this Call, 378 LoIs have been received by the Department. After two rounds of screening, total 10 projects have been recommended for financial support.  

    Further in this direction in order to address the rising threat of antimicrobial resistance (AMR) with a holistic and multi-sectoral (One Health) approach, “India’s One Health Initiative” to combat problems associated with AMR was launched on 18th February, 2019 in Delhi.

    Recently, India has partnered with Global AMR R&D Hub as a member of Board of Members. By partnering, with the Global AMR R&D Hub, the Department will work with all partners to leverage their existing capabilities, resources and collectively focus on new R&D intervention to address drug resistant infections.

    Significant Achievements:

    1. Dengue Day 1 test:
    2. Dengue Day 1 Test is a rapid solid phase immuno- chromatographic test for the qualitative detection of Dengue NS1 Antigen and differential detection of IgM and IgG antibodies to dengue virus in human serum / plasma. This test is for in vitro diagnostic use only and is intended as an aid to an early diagnosis of dengue infection & presumptive diagnosis between primary and secondary dengue infection. The disease is prevalent in third world tropical regions and spreading to sub-tropical developed countries - including the United States. WHO estimates that 50-80 million cases of dengue fever occur worldwide each year, including a potentially deadly form of the disease called dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).

      Primary infection with dengue virus results in a self-limiting disease characterized by mild to high fever lasting 3 to 7 days, severe headache with pain behind the eyes, muscle and joint pain, rash and vomiting. Secondary infection is the more common form of the disease in many parts of Southeast Asia and South America. Primary dengue virus infection is characterized by elevations in specific NS1 antigen levels 0 to 9 days after the onset of symptoms; this generally persistsupto 15 days. Earlier diagnosis of Dengue reduces risk of complication such as DHF or DSS, especially in countries where dengue is endemic.

      With support from DBT, the ICGEB team has designed and developed a highly sensitive, specific and yet highly affordable rapid dengue test. Unlike the other imported competitor's tests, this is capable of detecting dengue virus infection from Day 1 of fever. This three-in-one unique test detects all stages (first time or repeat episode) of dengue infections. The test is now a market leader with capturing >70% of the Indian market. It is purchased as bulk under the annual rate contracts by several states in India. It is also exported to several countries like Sri Lanka, Indonesia, Thailand Canada, USA, and a few African nations.

    3. SeeTB, क्षयदृष्टि:

    Traditionally, India has imported technologies, which is costly, rather than build its own. 25000+ primary healthcare centres in India still use cheap, not so effective sputum smear microscopy (SSM) method to diagnose TB. 36% of the cases undetected in SSM tests. An imported technology, GeneXpert tool costs Rs.12 Lakh which need uninterrupted electricity and AC. In such scenario, a Team led by IIT-Delhi has worked to build diagnostic platforms for cheaper and faster diagnosis for infections such as TB, Typhoid and gastroenteritis. SeeTB developed by an IIT-Delhi team which costs Rs. 50000/- with following salient features:

    • Portable and can be strapped on a microscope to enhance performance
    • Shortens sample analysis time by 1/10th
    • Improves diagnosis is rate to 80%

    Technologies Transferred & Commercialized:

    Outcome of Last 5 years

    State-wise Projects Funded

    National Facilities Supported:

    1. National Liver Disease Biobank (NLDB), ILBS, New Delhi: This is a first of its kind national biobank, executed as a joint initiative of Department of Biotechnology (DBT) and Institute of Liver & Biliary Sciences for translational research in liver and allied diseases.
    2. Advanced Technology Platform Centre (ATPC), RCB, Faridabad: ATPC has six operational platform facilities- Flow Cytometry Facility, Mass Spectrometry Facility, Protein Purification and Molecular Interactions Facility, Genomics Facility, Optical Microscopy Facility and Electron Microscopy Facility equipped with the various high-end technologies for aiding biotechnology start-ups and researchers.
    3. HIV Vaccine Translational Research (HVTR) Laboratory: The HIV Vaccine Translational Research (HVTR) Laboratory at THSTI has been carrying out early translational research and development under the joint partnership program between THSTI and the International AIDS Vaccine Initiative (IAVI). The HVTR laboratory has established capacity in isolating antigen-specific broadly neutralizing monoclonal antibodies (bnAbs) from peripheral blood mononuclear cells (PBMC) obtained from a well-defined HIV-infected elite neutralizer as a part of technology transfer under ongoing partnership program from the IAVI-Neutralizing Antibody Center (NAC). One patent entitled engineered recombinant protein antigen of trimeric mimic of hiv-1 envelope glycoprotein spike has been obtained under this project.
    4. Biobank facilities at National AIDS Research Institute (NARI), Pune: It is the first centralized state-of-art bio repository for access to biological samples across various stages of HIV-infection.

    COVID-19 Initiative:

    Today’s world witnesses the urgent international efforts to develop vaccines and other therapies for the current COVID-19 pandemic. Patient sample collection, processing, and analyses are at the forefront of this emergency.

    1. Therapeutic interventions:
    2. Considering current COVID crisis, the Department took immediate initiative on COVID-19 Research Consortium to support R&D efforts to tackle this infective agent through all sorts of technological interventions in terms of diagnostics, therapeutics, vaccines, repurposing of drugs and other mechanism to understand the clinical and pathological aspects of this pandemic agent.   Under this COVID Research Consortium, R&D efforts in Therapeutic sector do have significant value.  In order to check the significant burden of this pandemic infection, there is an urgent need to have some therapeutic interventions specific to this pathogen. Some of the proposals with good plan of work to target the pathogen are approved for initiating the work.

    3. Bio-bank:

    Although often operating in the background, bio-banking plays a critical role in the diagnosis and development of treatments for a variety of diseases. However, as the Bio-specimen issues have long been important factors in handling the response to emerging infectious diseases. Keeping a watch on the present situation, this pandemic is expected to continue to be the most critical international concern for years to come, from a public health perspective, as well as from the resulting economic impact. As the number of cases continues to mount, as well as the unfortunate loss of life, bio-banks will continue to work in the background to handle their roles in the response. From the perspective of Bio-preservation and Bio-banking, the role of bio-banks for COVID-19 samples can be envisaged as follows:

    a)  Development of a vaccine and treatments;

    b)  Guidance regarding handling, including nasopharyngeal swabs; and

    c)  Conditions under which the higher BSL-3 practices should be followed for example, when working with cultures of the coronavirus specimens. 

    The Department aims to support Bio-bank facility with well strategized future plan so that all sorts of technological interventions can be developed in due course of time. Towards this effort, the Department is exploring feasible facilities in already supported national bio-banks with immediate plan of work. As per the recent ICMR notification, following DBT institutions have been identified as designates bio-repository for COVID-19.

    S.N

    Institute

    1.

    NCR-Biotech Science Cluster,

    a.  Translational Health Science and Technology Institute (THSTI), Faridabad and

    b.  Regional Centre for Biotechnology (RCB), Faridabad

    2.

    Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore

    3.

    Institute of Life Sciences (ILS), Bhubaneswar

    4.

    National Centre for Cell Science (NCCS), Pune

    5.

    Institute of Liver and Biliary Sciences (ILBS), New Delhi (DBT-supported Bio-repository)

    Proposed Future Activities:

    • One-health approach to AMR: Antibiotics are used in a large number of health, veterinary, agriculture, animal husbandry, and food processing industry. AMR dynamics in the environment and novel strategies to identify and intervene are necessary for spread of AMR. Machine learning algorithm for prediction of antibiotic resistance and type of resistance.
    • Antibody as immuno-therapeutics: Since monoclonal antibodies as immuno-therapeutics are gaining momentum as they offer versatility, low toxicity, pathogen specificity, enhancement of immune function, and favourable pharmacokinetics, the Department has also envisioned spurring research and innovation in this area specifically targeting HIV, Influenza, AMR, RSV, and Snakebite.
    • Vector borne diseases:  Each year, millions of people in our country are disabled or killed by various vector borne diseases such as malaria, leishmania, dengue and chikungunya, a comprehensive and well strategized program is needed to develop in order to make our country free from these diseases.
    • Emerging and re-emerging infectious diseases: Considering the huge impact of these diseases, there is an immense necessity of accelerated efforts in this direction in order to support research on basic microbiology of and host response to these pathogens as well as development of medical countermeasures.
    • Sexually transmitted diseases (STDs) other than HIV: STDs are an important global health priority because of their devastating impact on women and infants and their inter-relationships with HIV/AIDS. Realizing this fact, accelerated efforts are needed to strategize towards the development of novel diagnostics, topical medications, and vaccines for STDs. 
    • Adjuvant discovery and development: There is a critical need for the identification and characterization of novel adjuvants to boost immunity and increase the efficacy of new or existing vaccines. A robust adjuvant program is needed to be initiated in both discovery and development mode with the ultimate goal of advancing candidate adjuvants towards licensure for human use.

    Other Major Initiatives launched during last FY:

    1. Drug Development Program
    2. India is a leader in global generic pharmaceuticals manufacturing. However, many generics manufactured in India are at the end of their respective product life cycle, with limited new research and development taking place on new drugs. Furthermore, our country has a high burden of both communicable and non-communicable diseases and is vulnerable to epidemics. In order to keep pace with global innovation and to improve health outcomes, there is a need to foster R&D for new and cost-effective therapies. With the aim to take India at global map in terms of R&D innovations in the area of drug development in our country, the Department has initiated a new program on “Drug Development” with a vision to develop indigenous and cost-effective new drugs against diseases prevalent in our country.

      With the announcement of this new program in its portfolio under Medical Biotechnology Program, the Department initiated major new efforts in the area of development of therapeutics.

      Major New Efforts:

      Department of Biotechnology (DBT) in collaboration with its Public Sector Undertaking, Biotechnology Industry Research Assistance Council (BIRAC) announced a Joint Call to invite proposals in the area of “Development of Drugs from existing leads with established proof of concept” against the following diseases:

      • Communicable Diseases
        1. Tuberculosis
      • Non-Communicable Diseases
        1. Cardio-Vascular Diseases (CVD),
        2. Chronic Obstructive Pulmonary Diseases (COPD) and
        3. Cancer (oral, head and neck, cervical and breast cancer)
    3. Mission- Next Generation Treatment for Snakebite (NGTS): Considering snakebites as one of the well-known medical emergencies in many parts of the world, especially in rural setup, World Health Organisation (WHO) has included snakebite into Category A of neglected tropical diseases. Since, India accounts around 50% of mortality and morbidity due to snakebite in the world, there is an immense need to support research and innovation for the development of health products for the patients of snakebite.
    4. Considering Snakebite Envenomation as a major problem in our country, the Department has initiated a major Mission program, Mission- Next Generation Treatment for Snakebite (NGTS) with a vision to develop an indigenous, cost-effective and globally accessible technology with the aim to cater the needs of the affected people and facilitate employment generation through training and skill development under Make-in-India and Skill India missions of the Government.
    5. Novel Monoclonal Antibody (mAb) based Immuno therapeutics: Considering Immuno-therapies an important area for disease management, and to tap the huge potential of novel antibody as immuno-therapeutics, Department has announced a Joint call with BIRAC on “Globally Accessible and Cost-Effective Novel Antibodies”. This programme aims to discover and develop cost affordable and globally accessible novel antibodies against Antimicrobial Resistance (AMR), Human Immunodeficiency Virus (HIV) and Snakebite Envenoming (SBE).  

    Contacts

    Programme HeadDr. Sundeep Sarin, Scientist G
    Emailsundeep[at]dbt[dot]nic[dot]in
    Phone No. 011-24362931
    Programme OfficerDr. Vinita N. Chaudhary, Scientist E
    Emailvinita[dot]chaudhary[at]nic[dot]in
    Phone No. 011-24362885
    Attached OfficerDr. Varshneya Singh, Scientist C
    Emailvarshneya[dot]singh[at]dbt[dot]nic[dot]in