Boosting DNA vaccine power by lipid nanoparticles surface engineered with amphiphilic bioresorbable copolymer

Chung-Hsiang Yang; Kuan-Yin Shen; Hui-Min Ho; Chiung-Yi Huang; Yu-Jhen Cheng; Chih-Chun Pu; Fang-Feng Chiu; Wan-Chun Huang; Hung-Chun Liao; Hsin-Wei Chen; Ching-Len Liao; Shih-Jen Liu; Ming-Hsi Huang

doi:10.1016/j.omtn.2024.102261

Boosting DNA vaccine power by lipid nanoparticles surface engineered with amphiphilic bioresorbable copolymer

Mol Ther Nucleic Acids. 2024 Jun 17;35(3):102261. doi: 10.1016/j.omtn.2024.102261. eCollection 2024 Sep 10.

Authors

Chung-Hsiang Yang¹, Kuan-Yin Shen¹, Hui-Min Ho¹, Chiung-Yi Huang¹, Yu-Jhen Cheng¹, Chih-Chun Pu¹, Fang-Feng Chiu¹, Wan-Chun Huang¹, Hung-Chun Liao¹, Hsin-Wei Chen^{1

2

3}, Ching-Len Liao¹, Shih-Jen Liu^{1

2

3}, Ming-Hsi Huang^{1

2

3

4}

Affiliations

¹ National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
² Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan.
³ Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁴ Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan.

Abstract

Successful DNA vaccination generally requires the aid of either a viral vector within vaccine components or an electroporation device into the muscle or skin of the host. However, these systems come with certain obstacles, including limited transgene capacity, broad preexisting immunity in humans, and substantial cell death caused by high voltage pulses, respectively. In this study, we repurposed the use of an amphiphilic bioresorbable copolymer (ABC), called PLA-PEG, as a surface engineering agent that conciliates lipid nanoparticles (LNPs) between stability during preparation and biocompatibility post-vaccination. The LNP carrier can be loaded with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific DNA; in this form, the DNA-LNP is immunogenic in hamsters and elicits protective immunity following DNA-LNP vaccination against heterologous virus challenge or as a hybrid-type vaccine booster against SARS-CoV-2 variants. The data provide comprehensive information on the relationships between LNP composition, manufacturing process, and vaccine efficacy. The outcomes of this study offer new insights into designing next-generation LNP formulations and pave the way for boosting vaccine power to combat existing and possible emerging infectious diseases/pathogens.

Keywords: ABC; COVID-19 vaccine; DNA delivery; LNP; MT: Delivery Strategies; amphiphilic bioresorbable copolymer; hybrid vaccination; lipid nanoparticle.