2. Academic Validation
  3. Chronological Management of Adjuvant Effect for Optimized mRNA Vaccine Inspired by Natural Virus Infection

Chronological Management of Adjuvant Effect for Optimized mRNA Vaccine Inspired by Natural Virus Infection

  • ACS Nano. 2024 Jul 16. doi: 10.1021/acsnano.4c04953.
Zeliang Lou 1,  Yingying Shi 1,  Xuemeng Guo 1,  Zhaolei Jin 1,  Jiaxin Huang 1,  Yilong Hu 1,  Xu Liu 1,  Jiang Zhu 2,  Rong Kuang 3,  Jian You 1 4 5 6
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China.
  • 2 Department of Ultrasound, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P. R. China.
  • 3 Zhejiang Institute for Food and Drug Control, 325 Pingle Street, Hangzhou, Zhejiang 310004, P. R. China.
  • 4 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang 310006, P. R. China.
  • 5 The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang 310006, P. R. China.
  • 6 Jinhua Institute of Zhejiang University, 498 Yiwu Street, Jinhua, Zhejiang 321299, P. R. China.
PMID: 39011561 DOI: 10.1021/acsnano.4c04953
Abstract

The efficacy and safety of mRNA vaccines both rely on a fine-tuning of specific humoral and cellular immune responses. Instead of adjustments in vaccine component, we proposed a concept of chronological management of Adjuvant effect to modulate the adaptive immune potency and preference inspired by natural virus Infection. By simulating type I interferon expression dynamics during viral Infection, three vaccine strategies employing distinct exposure sequences of Adjuvant and mRNA have been developed, namely Precede, Coincide, and Follow. Follow, the strategy of Adjuvant administration following mRNA, effectively suppressed tumor progression, which was attributed to enhanced mRNA translation, augmented p-MHC I expression, and elevated CD8+ T cell response. Meanwhile, Follow exhibited improved biosafety, characterized by reduced incidences of cardiac and liver toxicity, owing to its alteration to the vaccination microenvironment between successive injections. Our strategy highlights the importance of fine-tuning Adjuvant effect dynamics in optimizing mRNA vaccines for clinical application.

Keywords

adjuvant effect; cardiac and liver toxicity; chronological management; mRNA vaccine; vaccine efficacy.

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