A research team led by Professor Yong Taik Lim at the Sungkyunkwan Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, has developed a next-generation vaccine platform that mimics the multidimensional immune responses induced by natural infections, providing long-term and broad protection against various viral infections.

In this study, the researchers successfully developed a Kinetically Engineered Vaccine (KE-VAC) that mimics the key immunological features of recovered patients. At the microscopic level, the team regulated the timing of action of Toll-like receptor (TLR) agonists, and at the macroscopic level, they controlled the supply kinetics of antigens and adjuvants, thereby inducing immune responses similar to those observed in natural infection. The vaccine enables prolonged activation of antigen-presenting cells (APCs) without exhaustion and enhances both antibody production and T cell responses by extending the interaction time within the lymph nodes.

This research was published online in the world-renowned journal Nature Communications (IF = 14.7) on March 25, 2025.

Conventional artificial vaccines primarily use single antigens or universal adjuvants such as aluminum (Alum) to induce stable antibody responses. However, they fall short of replicating the complex immune responses seen in natural infections, resulting in limited T cell activation and insufficient long-term protection. To overcome these limitations, the team designed a kinetically activated TLR7/8 agonist (m-TLR7/8a), which was encapsulated in nanoliposomes and formulated with Alum to enable gradual delivery of both antigens and immune signals to the lymph nodes. This formulation mimics the gradual replication of pathogens in vivo, successfully inducing sustained immune responses in lymph nodes for up to six weeks.

The KE-VAC platform demonstrated strong humoral and cellular immune responses in animal models using model antigens such as OVA. Furthermore, in collaborative studies with the Korea Virus Research Institute (Director: Young Ki Choi) and the College of Veterinary Medicine at Chungnam National University (Professor Jong-Soo Lee), KE-VAC showed exceptional and long-lasting protective efficacy against spike proteins from SARS-CoV-2, the sM2HA2 antigen from influenza viruses, and the SFTS virus through both immune response analysis and survival studies.

KE-VAC can simultaneously induce both antibody and T cell responses through a single formulation, making it a highly versatile immune platform that can be quickly adapted to emerging infectious diseases or viral variants. Its ability to replicate the depth and durability of immune responses observed in natural infection highlights its promise not only for infectious disease prevention but also for next-generation cancer vaccine development.

Author: Sang Nam Lee (1st authof, Postdoctoral Researcher), Ryounho Eun (co-1st author, Researcher), Sei Hyun Park (Co-author, Ph.D student), Janghun Heo (Co-author, Ph.D student), Yong Taik Lim (Corresponding Author, Professor, Sungkyunkwan University)

Title: Kinetically activating nanovaccine mimicking multidimensional immunomodulation of natural infection for broad protection against heterologous viruses in animal models (Nature Communications; IF=14.7, March 25, 2025)