The Transformative Potential of Lipid Nanoparticle-Protein Corona for Next-Generation Vaccines and Therapeutics

Abstract

The integration of the lipid nanoparticle (LNP)-protein corona as a pioneering approach for the development of vaccines against the present and future SARS-CoV-2 variants of concern marks a significant shift in the field. This concept holds great promise, offering a universal platform that can be adaptable to combat future pandemics caused by unknown viruses. Understanding the complex interactions among the protein corona, LNPs, and receptors is crucial for harnessing its potential. This knowledge will allow optimal vaccine formulations and improve their effectiveness. Safety assessments are essential to ensure suitability for human use, compliance with regulatory standards, and rigorous quality control in manufacturing. This transformative workflow requires collaborative efforts, expanding our foundational knowledge and translating advancements from the laboratory to clinical reality. The LNP-protein corona approach represents a paradigmatic shift with far-reaching implications. Its principles and insights can be leveraged beyond specific applications against SARS-CoV-2, enabling a universal platform for addressing viral threats, cancer, and genetic diseases.

Keywords: SARS-CoV-2; lipid nanoparticle; protein corona; vaccination.

Figure 1

Cartoon underscores the primary challenges and drawbacks associated with LNP vaccines, while also highlighting potential opportunities. One significant opportunity lies in the ability to modify the protein corona composition, which can help mitigate off-target accumulation and enhance the interaction of LNPs with antigen-presenting cells and dendritic cells. This, in turn, has the potential to significantly improve vaccine efficacy.

Figure 2

DNA vaccines targeting SARS-CoV-2 can be created through recombinant DNA technology, utilizing the commercially available pcDNA3.1-SARS2-Spike plasmid (e.g., obtained from Addgene, MA) as the template. A DNA plasmid encoding the extracellular domain of the spike protein is loaded into a lipid nanoparticle (LNP). Next, the production of LNP-protein corona DNA vaccines will follow, achieved by incubating DNA-loaded LNPs with donor-derived interstitial fluid (DIF) obtained from healthy human volunteers, employing standardized protocols. The protein corona will consist of numerous proteins, here represented by a single green protein for simplicity. Our focus will shift toward exploiting the protein corona as a natural targeting entity, with particular attention to certain proteins, known as protein corona fingerprints (PCFs), which hold promise as potential targeting ligands. The internalization of LNP-protein corona DNA vaccines into target cells, such as antigen-presenting cells (APCs) and dendritic cells (DCs), ensues via a receptor-mediated mechanism. Protein corona fingerprints lock onto receptors of APCs stimulating massive vaccine internalization, which then churns out copies of the virus’s spike protein. Activation of adaptive immunity leads to the production of neutralizing antibodies and cell-mediated immune responses against SARS-CoV-2. For simplicity, the cell-mediated immune response is not depicted in the figure, but for a complete description, the reader may refer to.