What is it about?
We developed a new approach to improve nucleic acid vaccine that works by encoding a specific antigen that can be expressed in the body post vaccination. The improvement was achieved through reducing degradation of the nucleic acid, based on treatment of cells with sucrose that transiently inhibited lysosome function. As an application, we showed that the new approach could substantially increase intracellular expression of influenza viral antigen post DNA vaccination, which in turn led to higher immune responses to the antigen and better protection of animals against viral challenge.
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Why is it important?
The antigen expression level can be increased by increasing the DNA vaccine dose or reducing the DNA degradation in cells. The latter is more effective than the former since we demonstrate that to achieve the same expression level, the sucrose treatment is equivalent to increasing the vaccine dose by about 3000 folds, which is clinically impractical due to material restrictions and severe toxicity caused by the DNA at such a high dose.
Perspectives
I hope the study demonstrates that improving nucleic acid transport in cells is an important consideration in development of nucleic acid vaccines. Sucrose is non-toxic, inexpensive, and widely available. Thus, the approach developed in this study can be applied directly to improving clinical applications of nucleic acid-based vaccines and other therapeutics.
Dr. Fan Yuan
Duke University
Read the Original
This page is a summary of: Transient inhibition of lysosomal functions potentiates nucleic acid vaccines, Proceedings of the National Academy of Sciences, October 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2306465120.
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