IIT Kanpur Scientists Research Reveals How a Promising Vaccine Booster Switches on Immune Cells

Researchers at the Indian Institute of Technology (IIT) Kanpur have exposed how an experimental molecule called EP67 switches on an imperative receptor found on human immune cells. EP67 is a candidate adjuvant, an element added to vaccines to make them work better. The finding, published in the journal Proceedings of the National Academy of Sciences (PNAS), gives scientists the first clear, close-up view of EP67 gripping its target, and hands them a blueprint for intended safer vaccines and novel immune-based management.

When they catch a bacterial or viral infection, immune cells release a small protein called C5a, which activates the immune system to fight back. However, too much C5a for too long leads to inflammation, which is harmful and damages healthy tissue. To prevent this, the body uses enzymes in the blood to break C5a down rapidly once the hazard has passed.

The investigators at IIT Kanpur took a cue from this natural safety mechanism and built a stripped-down copy of C5a, a short chain of just 10 amino acids named EP67, that keeps the useful part of C5a's activity but works more gently. It wakes up 2 kinds of immune cells, dendritic cells and macrophages, which support the body in building lasting protection. At the same time, it barely moves neutrophils, the cells most responsible for the unwanted inflammation. This is precisely what is required in a vaccine booster: a potential, longer-lasting immune response deprived of the collateral damage.

Earlier animal research supports this when EP67 was added to vaccines against some viruses in mice, involving the virus that causes COVID-19; the animals mounted a stronger immune response than with the vaccine alone and also tended to recover quickly. EP67 has shown an amazing ability to fight bacterial infections, such as MRSA, a strain of staph that is resistant to the most common antibiotics.

The IIT Kanpur team also found the mechanism of action of EP67; as deprived of meaningful information about its precise target, researchers could not enhance the molecule or shift it confidently toward the clinic. EP67 binds to and activates a receptor known as C5aR1, a member of a large family called G protein-coupled receptors, or GPCRs. These receptors sit in the outside membrane of cells and relay signals inward, and they are the single biggest group of drug targets in the body. Around 1 in 3 prescription therapeutics works by acting on a GPCR.

To pin this down, the scientists first grew human cells in the lab and confirmed that EP67 turns C5aR1 on, via a milder effect than C5a does. They then applied cryo-electron microscopy, a technology that flash-freezes molecules and images them in near-atomic detail, to capture EP67 locked in the receptor. The pictures revealed that EP67 folds into a hook shape that slots into a space at the center of the receptor and switches it on.

This level of precision in how EP67 fits its target has enabled the team to intend it, adjust the amino acid sequence to make the molecule sturdier, and advance toward hitting its mark. From here onwards, the next steps would be refining the formulation and dosing in pre-clinical tests.

The research led by the laboratory of Professor Arun K. Shukla in the Department of Biological Sciences and Bioengineering at IIT Kanpur was published in PNAS in July 2026. Donors from Professor Shukla's lab include Annu Dalal, Manish Yadav, Sudha Mishra, Manisankar Ganguly, Shachie Sinha, Nabarun Roy, Divyanshi Tiwari, Debdatta Mukherjee, Nilanjana Banerjee, and Ramanuj Banerjee. The work also drew on the laboratories of Professor Cornelius Gati at the University of Southern California and Professor Trent Woodruff at the University of Queensland, Australia.
The scientist was supported by the Indian Council of Medical Research (ICMR), the Anusandhan National Research Foundation (ANRF), the Department of Biotechnology (DBT), and the Department of Science and Technology (DST). The high-resolution structure was determined at the National cryo-EM Facility at IIT Kanpur, set up with funding from ANRF.

According to Towards Healthcare, the vaccine adjuvants market is projected to experience significant growth, with estimates suggesting the market size will increase from USD 795.67 million in 2026 to approximately USD 1394.15 million by 2035, representing a compound annual growth rate (CAGR) of 6.43% from 2026 to 2035, driven by, adjuvants supports overcome weakened immune responses experiential in certain population groups, like the ageing or infants. Adjuvants support overcoming this restraint by more efficiently stimulating the immune system, leading to enhanced protection in these vulnerable populations. The increased effectiveness of vaccines containing adjuvants significantly lessens the number of doses required to achieve adequate protection. Adjuvants extend the duration of the immune response, which leads to long-term defense against the disease.

About Indian Institute of Technology (IIT) Kanpur

IIT Kanpur has been at the forefront of research in science and technology. The various backgrounds and proficiency of IIT Kanpur faculty span engineering, humanities, sciences, and management, confirming a holistic and multidisciplinary strategy to education and research. The Indian Institute of Technology Kanpur (IIT Kanpur or IITK) is a public institute of technology located in Kanpur, Uttar Pradesh, India. As an Indian Institute of Technology (IIT), it was declared an Institute of National Importance by the Government of India under the Institutes of Technology Act.

A recent report by Towards Healthcare highlights that the vaccine adjuvants market is growing, as adjuvants support the body to produce an immune response strong enough to protect the person from the disease he or she is being immunized against. Adjuvants support the body to produce an immune response strong enough to defend the person from the disease is being vaccinated against. Adjuvanted vaccines cause more local reactions like redness, swelling, and pain at the injection site and more systemic reactions including fever, chills, and body aches than non-adjuvanted vaccines. Vaccine adjuvants rouse and amplify the body's immune response to the antigen contained in the vaccine. They act by stimulating different immune pathways, involving the activation of antigen-presenting cells (APCs) and the production of inflammatory cytokines. They therefore encourage increased antibody production and T-cell response, thus improving the overall effectiveness of the vaccine.