Kinetically activating nanovaccine mimicking multidimensional immunomodulation of natural infection for broad protection against heterologous viruses in animal models

Sang Nam Lee, Young-Il Kim, Jaemoo Kim, D. K. Haluwana, Ryounho Eun, Sei Hyun Park, Janghun Heo, Juryeon Gil, Yebin Seong, Min-Ho Lee, Young-Woock Noh, Jong-Soo Lee (), Young Ki Choi () and Yong Taik Lim ()
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Sang Nam Lee: Sungkyunkwan University
Young-Il Kim: Korea Virus Research Institute (KVRI), Institute for Basic Science (IBS)
Jaemoo Kim: Korea Virus Research Institute (KVRI), Institute for Basic Science (IBS)
D. K. Haluwana: Chungnam National University
Ryounho Eun: Sungkyunkwan University
Sei Hyun Park: Sungkyunkwan University
Janghun Heo: Sungkyunkwan University
Juryeon Gil: Korea Virus Research Institute (KVRI), Institute for Basic Science (IBS)
Yebin Seong: Chungnam National University
Min-Ho Lee: Osong Medical Innovation Foundation
Young-Woock Noh: Osong Medical Innovation Foundation
Jong-Soo Lee: Chungnam National University
Young Ki Choi: Korea Virus Research Institute (KVRI), Institute for Basic Science (IBS)
Yong Taik Lim: Sungkyunkwan University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Immunity by vaccination can protect human against heterologous viruses. However, protective abilities of artificial vaccines are still weaker than natural infections. Here we develop a kinetically engineered vaccine (KE-VAC) that mimics the multidimensional immunomodulation in natural infections via dynamic activation of antigen presenting cells with masked TLR7/8 agonist and sustained supplies of antigens and adjuvants to lymph nodes, leading to follicular helper T and germinal centre B cell activation in vaccinated mice. KE-VAC demonstrates superior efficacy than traditional alum and mRNA vaccines, achieving a 100% survival rate with increased neutralizing antibodies titers and polyfunctional CD8+ T cells, recognizing heterologous SARS-CoV-2 variants, and inducing broad and long-term protection against multiple strains of influenza viruses. Prime/boost vaccination with KE-VAC also protect aged ferrets from severe fever with thrombocytopenia syndrome virus infection, with no virus detected in any organs at day 6 p.i. The efficacy of KE-VAC across various pathogens thus highlights its potential as an effective vaccine against emerging infectious risks.

Date: 2025
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DOI: 10.1038/s41467-025-58006-y

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