Long-term stability and immunogenicity of lipid nanoparticle COVID-19 mRNA vaccine is affected by particle size

ABSTRACT

Messenger ribonucleic acid (mRNA) technology has been rapidly applied for the development of the COVID-19 vaccine. However, naked mRNA itself is inherently unstable. Lipid nanoparticles (LNPs) protect mRNAs from extracellular ribonucleases and facilitate mRNA trafficking. For mRNA vaccines, antigen-presenting cells utilize LNPs through uptake to elicit antigen-specific immunity. There are reports on the impact of various physical characteristics of LNPs, particularly those with sizes less than 200 nm, especially 50 to 150 nm, on the overall stability and protective efficacy of mRNA vaccines. To address this, a single change in the size of LNPs using the same mRNA stock solution was assessed for the physicochemical characterization of the resulting mRNA-LNPs vaccine, along with the evaluation of their protective efficacy. Particles of smaller sizes generally disperse more effectively in solutions, with minimized occurrence of particle precipitation and aggregation. Here, we demonstrate that the vaccine containing 80–100 nm mRNA-LNPs showed the best stability and protection at 4°C and −20°C. Furthermore, we can conclude that freezing the vaccine at −20°C is more appropriate for maintaining stability over the long term. This effort is poised to provide a scientific basis for improving the quality of ongoing mRNA vaccine endeavors and providing information on the development of novel products.

GRAPHICAL ABSTRACT

KEYWORDS:

• mRNA vaccine
• SARS-CoV-2
• lipid nanoparticle
• particle size
• stability
• biological activity

Acknowledgments

This work was done with contributions from all authors.SR and LX conceived the project and provided discussions.ML and WS performed the experiments and visualized the data. WY and SL contributed to the analysis of the data. All authors have approved the final version of the manuscript. The authors would like to thank all the reviewers who participated in the review, as well as the MJ Editor for providing English editing services during the preparation of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics statement

The researchers diligently adhered to the “Guidelines for the Care and Use of Laboratory Animals” set forth by the National Research Council’s Committee on Life Sciences. The mouse studies were conducted under protocols approved by the Animal Care and Use Committee of the Hebei Drug and Medical Device Inspection Institute. All animal experiments were carried out following national and local policies and were conducted within facilities accredited by the China Association for Laboratory Animal Care and Accreditation (AAALAC), ensuring the proper care and maintenance of animals.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2024.2342592

Additional information

Funding

This study was supported by the Hebei Provincial Key Research and Development Project Program, the Hebei Institute of Medical Device Inspection, North China Pharmaceutical Biotechnology Co. Ltd, and CSPC Zhong Qi Pharmaceutical Technology Co. Ltd.