India Alliance Grantee Spotlight: Dr. Jayanta Bhattacharya

“We must invest in a one-health approach, in which multiple sectors communicate and work together to achieve better public health outcomes. With the surge in zoonotic diseases, it is also imperative to focus research on these diseases, and ensure that existing platforms and technologies, such as those developed for HIV, can be translated for emerging diseases, as we saw in the case of the COVID pandemic” says Jayanta Bhattacharya, this month’s India Alliance Grantee in Spotlight. Read this interview to learn more about his team’s research on prevention and therapy in HIV/AIDS, the role of India Alliance Team Science Grants in the achievements of the research group, interventions to manage infectious diseases, and more!

HVTR Director Jayanta Bhattacharya examining HIV infected cells through an inverted microscope at the HVTR Lab in Faridabad, India.

Let us begin with talking about your research. What are you currently working on and what impact do you envision with your work?

Our research is primarily focussed on understanding how circulating HIV diversity can impact antibody mediated prophylaxis and therapy. Our research primarily deals with HIV-1 clade C, which is the predominant subtype of HIV-1 circulating in India, and accounts for nearly 50% of global infection. We study the genetic basis of evolving diversity of the HIV-1 (both intra and inter-subtype diversities), with reference to viral envelope (env) spike gene, while also focussing on identifying broadly neutralizing human monoclonal antibodies (bnAbs) isolated from individuals in the course of infection that can overcome this enormous diversity. We are currently working to dissect the genetic variability of the circulating HIV-1 across different geographies, risk groups, and key populations, with and without comorbidities, vis-à-vis understanding neutralization diversity of the currently circulating HIV-1.

Our research will inform the choice and prioritization of bNAb combinations that can effectively dissect the circulating HIV-1 clade C diversity and help develop affordable bnAbs through further engineering and optimization for prevention and treatment over and above the existing antiretroviral drug therapy. Our laboratory at Translational Health Science and Technology Institute (THSTI), one of the R&D laboratories of IAVI along with different regional institutions, works very closely with our strong global network of research partners at different institutions in Africa, and other regions, to complement our research endeavour.

As our work mainly centres around translational aspects, we envision to translate our scientific discoveries into products that will have an impact on reducing the burden of HIV, either through preventive or therapeutic interventions.

You recently published an exciting study in PLOS Pathogens. Tell us more about it.

The work that we published in PLOS Pathogens is a result of multi-institutional collaboration led by us. We carried out this study based on our hypothesis that in the natural course of infection, the interplay between circulating virus (HIV) variants and broadly cross neutralizing antibodies developed in a subset of rare individuals (also referred to as elite neutralizers) would provide strategies for rational immunogen design.

In this particular study, we looked at the structural, antigenic and immunogenic properties of a thermostable and soluble trimeric HIV-1 envelope protein (Env) that we prepared based on a primary HIV-1 env (gp160) subtype C sequence (which we isolated from one Indian elite neutralizer). This novel trimeric Env trimer antigen demonstrated comparable antigenic, structural, and immunogenic properties that favoured several ongoing subunit vaccine design efforts, including ones that are in Phase 1 clinical trial. Very interestingly, and to our surprise, based on high resolution electron micrography, we found this novel HIV antigen induced potent neutralizing antibody response in rabbits with specificity comparable to the one mounted in the human elite neutralizer.

Our findings highlight that a better understanding of how vaccine-induced polyclonal neutralizing antibody responses compares to responses that developed in natural infections will improve our knowledge in designing better vaccine design strategies in the future.

We are now facing another massive peak in COVID infections. If you were to list three key lessons for our approach to managing infectious diseases, what would they be?

In my opinion, the three key lessons for our approach to managing infectious diseases include:

Rapidly developing pandemics necessitate rapid responses. We must invest in research on rapid diagnostics and next generation platform tools (such as genetic sequencing), vaccine approaches, and their uptake (the latter through raising awareness about hesitancy).

We have seen the emergence of a few new variants, which have contributed to the rapid spread of the virus in India. For this reason, genomic surveillance (both epidemiological as well laboratory) and mapping of infectious disease outbreaks in human populations, and their impact on human lives, is important. Subsequently, policy implementation must be evidence-driven; bridging the gap between evidence generation, dissemination of scientific information, and policy implementation is crucial.

We must invest in a one-health approach, in which multiple sectors communicate and work together to achieve better public health outcomes. With the surge in zoonotic diseases, it is also imperative to focus research on these diseases, and ensure that existing platforms and technologies, such as those developed for HIV, can be translated for emerging diseases, as we saw in the case of the COVID pandemic.

Are you beginning to see the effect of COVID-19 on other major public health challenges—like HIV, Tuberculosis, Malaria?

We can see, quite clearly, that our existing health systems are being put under an immense amount of pressure because of the COVID-19 pandemic. This has had, and what I think will continue to have, ramifications on other major health public health issues like HIV, TB, and malaria because of disruptions to preventive and curative health services for key affected populations. Additionally, the socioeconomic and psychological impact of COVID-19 on these vulnerable populations cannot be undermined. For instance, one study from the United States highlighted decreased quality of life, increased anxiety, decreased access to basic needs, fewer sexual partners, and increased use of recreational drugs due to COVID-19 in men having sex with men (MSM).

While data suggests that people living with HIV (PLHIV) who are on effective treatment have the same risk of having COVID-19 as people who do not have HIV, several studies show that PLHIV are at greater risk of mortality from COVID-19. The only large study so far from South Africa (a country with highest prevalence of HIV) found that PLHIV were two-to-three times more likely to die from COVID-19, even after considering the impact of known risk factors such as age and diabetes. Further, PLHIV who are not on treatment, or who are not virally suppressed, may have a compromised immune system and may be at a greater risk of acquiring SARS-CoV-2 infection.

The synergistic effect of COVID-19 and HIV has not been studied extensively yet, and this could be crucial as it may or may not have implications on the disease progression of either disease. This becomes pertinent to India with the third largest HIV-epidemic in the world with 2.1 million people living with HIV, of which only 56% are on antiretroviral therapy (ART) and also grapple with tuberculosis and other comorbidities (cardiovascular diseases, diabetes, and obesity, among others).

It is therefore important that we must prioritize maintaining these preventive and curative services for at-risk populations and reduce the overall impact of COVID-19.

The current pandemic underscores the need for collaborative science including better cooperation at the science–policy–society interface. What systemic interventions do you think can meaningfully facilitate this?

I would imagine the following directions that would possibly facilitate the research collaboration in a meaningful way and would also be productive.

Firstly, the scientific community must continue to share knowledge and data to promote collaborative research and ensure that scientific information is more accessible, especially in the context of low- and middle-income countries (LMIC) where technological, infrastructural and policy barriers may hinder this knowledge creation. Secondly, it is very important to strengthen national capacities for science-based decision making. Thirdly, it is important to continue to promote a multi-sectoral, private-public partnership model, much like on the lines of the Coalition for Epidemic Preparedness Innovations (CEPI) mission, in order to ensure that lifesaving therapeutics and vaccines are reaching those people who most need them. Finally, public trust and confidence in science is critical to the science-policy-society interface and is key for science-based policies to succeed. Therefore, I think it is imperative for governments, and scientific organizations, to engage transparently with the public to ensure that the correct information is being disseminated in the public sphere.

How has the India Alliance Grant helped you with your research goals so far? Could you share some tips for potential aspirants of the Team Science Grants?

The Team Science Grant has helped us immensely in bringing research groups with complementary and diverse skill sets together to optimally address our research goals. Our team comprises of unique scientific leaderships from different institutions with specialization in molecular virology, immunology, bioinformatics, structural biology, virus, and antibody deep sequencing and analysis. Additionally, it has given us an opportunity to collaborate with clinicians, stakeholders and epidemiologists, with cross disciplinary expertise across different regions of India, towards achieving our goal.

The Team Science Grant provides a unique opportunity to make use of interdisciplinary strengths and efforts critical for cutting edge scientific discovery and translational research outcomes. It is therefore important for those who plan to apply for the grant to ensure that they identify highly integrated and interactive research teams, who could share several features that contribute to success within multidisciplinary research projects over time. It is also important to ensure that lead scientists, and other co-investigators, can develop a shared vision, build as strong a team as possible with a clear purpose, strategically identify team members who can bring in distinct skill sets to complement and contribute significantly. Additionally, the team should promote a healthy environment with clear expectations for sharing credit and authorships.

What is the one thing you would like to change about the research culture in India and one thing you would not want to?

The one thing I would like to highlight within research culture in India is enabling the creation of a safe environment for researchers to express their ideas, making it more financially attractive, and providing more transparency to attract a large talent pool. Subsequently, this could also mean providing adequate opportunities for talent returning to India from other countries. Given our line of work, I would also urge the promotion of translational research as a separate domain and facilitate public-private partnerships that will help in supporting these programs. There should also be a greater, and continued, emphasis on science communication with the public.

There is already a consortium like approach to research in India, one which emphasizes on broader vision and ensures access to resources, including technologies and technical know-how. This approach must continue to be leveraged.

Has the pandemic changed how a typical day of your research activities looks like? If so, how?

The pandemic indeed has changed what a typical day of our research activities looks like for us; we are adapting to a more hybrid way of working. Also, with constant lockdowns and curbs on movement, most of the researchers and lab members who form our team are largely forced to stay put at home. There are virtual interactions and brainstorming on scientific ideas, but execution to fullest capacity remains a challenge currently.

What do you look forward to the most, once things get better?

Amongst the few things that I am very much looking forward to once things get better is having our lab working in full swing, and full work force, with people coming to the lab more consistently without any apprehension and fear. I also want to resume visiting our partner laboratories and clinical sites, which are an integral part of our research endeavour. Additionally, I look forward to returning to attending the in-person meetings and conferences that I have missed dearly due to the pandemic restriction.

This interview was originally published by DBT/Wellcome Trust India Alliance.