The vaccine efforts of the COVID-19 pandemic highlighted our knowledge about gaps in the immune system. Reductionist systems, such as genetically identical inbred mice, have long been the choice for immunology research, which focuses on studying the cells, tissues, and organs that make up the immune system. However, the spotlight has shifted to unravelling the complexities of the human immune system. This article outlines the challenges of conducting human immunology research in a developing country.
A different approach to study the human immune system
While model animals are valuable tools, it is apparent that they may not always accurately predict the behaviour of the human immune system. The TGN 1412 trial serves as a great example, where a drug deemed safe in animals resulted in life-threatening consequences when tested at a much lower dose in humans. Another reason to focus on human immunology is the heterogeneity in immune responses, which may not be accurately reflected in model organisms. Therefore, it is particularly valuable to characterise the baseline as well as the breadth of immune responses in India, which includes people from different ethnic groups, ages, dietary patterns, and socioeconomic backgrounds. Lastly, India faces a significant burden of tropical diseases, such as dengue, chikungunya, and malaria, and also faces a threat from emerging or rare infectious diseases. Thus, understanding the human immune system is crucial for improving disease management strategies and being prepared for future outbreaks.
Studying immune cells
The most accessible source of immune cells is blood, and a significant portion of human immunology research has been conducted using blood samples obtained from participants in regulated, ethically conducted studies with informed consent. Studying immune cells in the blood can provide insights into their behaviour and role in pathogen control. However, blood cells do not present the entire picture. Many immune cells in tissues may look and behave differently from cells in the blood, and some immune cells never enter the circulation and reside in tissues. Characterising immune cells in human tissues, such as lymph nodes obtained from surgical waste during living donor transplants or biopsies remaining after clinical use, has proven useful in addressing this gap. More recent studies have also utilised samples from recently deceased organ donors who consented to research. The advantage of using such samples over surgical explants or biopsies has been highlighted in the work by Dr Donna Farber’s group (PMID 28719147), which is not discussed in detail here.
Immunology studies in India: Steps we can take
Human immunology studies in India require several key components to support high quality research, including a regulatory framework, effective clinic-research lab partnerships, infrastructure, and funding. Recognising this, some upcoming research institutes in India have invested in these aspects to support scientists interested in human immunology.
A robust regulatory framework is necessary to address the ethical and biosafety considerations unique to human sample research. While regulatory bodies for this purpose already exist, it is essential to establish rigorous yet reasonable rules governing human subject research. High-quality training modules, contextualised for scenarios encountered in India and available in multiple languages, are crucial for training personnel at all levels to execute research with high standards. Institutional support, such as expert consultants, essential document templates, and protocols for regulatory submissions, is also vital. Finally, public engagement in research has to be sought through informal group sessions communicating the purpose of the human research in plain language.
Similarly, institutes that facilitate connections between local hospitals and research institutes play an essential role. India boasts a large community of qualified physicians and scientists, but fostering more synergistic associations between the two is necessary. This can be achieved through the creation of short-term paid positions for clinicians to train with research groups and for research groups to engage in medicine or public health-related community service. Although collaborations of this nature already exist, they tend to be concentrated in major cities. To enhance outbreak preparedness and gain valuable local information, it is important to extend these networks to smaller research institutes and hospitals in towns and rural areas.
The requirement for infrastructure encompasses not only specialised equipment but also the substructure necessary to support that equipment over an extended period. For example, frequent power outages can impact the lifespan of equipment, and backup power may not be sufficient to support power-consuming instruments. Purchasing energy-efficient equipment, rather than solely considering the lowest cost, could potentially reduce strain on power consumption.
Immunology research heavily relies on consumable reagents, such as fluorochrome-coupled monoclonal antibodies, MHC tetramers, and various types of tissue culture tubes and plates. Currently, these reagents are mostly imported through distributors, adding significantly to the cost of experiments (due to refrigerated shipping costs and import duties). Another hidden cost is the time taken for reagents to reach the lab, or in some cases, the reagents not clearing customs at all. To alleviate these challenges, local production of such reagents would reduce costs, shorten delivery times, and stretch research budgets further. However, one hurdle to local production is that reagents not involving innovation or point-of-care products are not considered market-worthy. Moreover, human immunology research in India is considered too small a market. To break this cycle of no supply no demand, increased funding for local production of research reagents by academic units (when intellectual property is not a concern) is necessary, not just for point-of-care devices or novel technologies.
Human immunology research holds promising potential in India, but it requires a collective scientific will, collaborations and increased clinical and research partnerships to gain momentum. By fostering these partnerships, investing in infrastructure and regulatory frameworks, and supporting local production of research reagents, India can pave the way for significant advancements in understanding the human immune system. This knowledge will not only contribute to better disease management strategies but also ensure preparedness for future outbreaks, benefiting the health and well-being of the Indian population and beyond.