Manganese-Coordinated Lipid Nanoparticles for Co-Delivery of VZV Antigen and CpG Adjuvant Enhance Vaccine Efficacy
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Compuscript Ltd
2025-05-01
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| Series: | Zoonoses |
| Online Access: | https://www.scienceopen.com/hosted-document?doi=10.15212/ZOONOSES-2024-0056 |
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| Summary: | <div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section">
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<h5 class="section-title" id="d1449262e134">Objective:</h5>
<p dir="auto" id="d1449262e136">Because varicella zoster virus (VZV) infections are continually increasing, vaccine
efficacy must be enhanced. To date, the inefficient in vivo utilization of antigens
and adjuvants has limited vaccine-induced immune protection against VZV infection.
Therefore, improving the antigen and adjuvant utilization efficiency is crucial to
enhance VZV vaccine performance.
</p>
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<h5 class="section-title" id="d1449262e139">Methods:</h5>
<p dir="auto" id="d1449262e141">To achieve favorable VZV antigen and adjuvant utilization efficiency, we constructed
a co-delivery system based on manganese-coordinated lipid nanoparticles (Mn-LNPs).
Palmitic acid was coordinated with manganese through hydrothermal synthesis. Furthermore,
1.6 molar palmitic acid-Mn was added to four commercial lipid nanoparticle components
(SM-102:DSPC:CHO-HP:DSG-PEG2000 in a 50:10:37.5:2.5 molar ratio) to encapsulate VZV
glycoprotein E (gE) antigen and CpG adjuvant by using a microfluidic chip. We characterized
Mn-LNP size and morphology through transmission electron microscopy and quantified
the manganese on palmitic acid-Mn through X-ray photoelectron spectroscopy. We also
evaluated the performance of the Mn-LNP co-delivery system in enhancing VZV vaccine-induced
immune responses in a mouse model.
</p>
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<h5 class="section-title" id="d1449262e144">Results:</h5>
<p dir="auto" id="d1449262e146">The Mn-LNPs comprised positively charged spherical particles of approximately 270
nm in diameter, which encapsulated VZV gE antigen and CpG adjuvant in a 1:2 mass ratio.
The Mn-LNP co-delivery system, compared with aluminum adjuvant, significantly enhanced
VZV gE antigen-specific CD4
<sup>+</sup> and CD8
<sup>+</sup> T cell responses (1.47-fold and 5.66-fold enhanced IFN-γ response for CD4
<sup>+</sup> T cells and CD8
<sup>+</sup> T cells; 2.25-fold and 2.64-fold enhanced TNF-α response for CD4
<sup>+</sup> T cells and CD8
<sup>+</sup> T cells; and 2.62-fold and 3.17-fold enhanced IL-2 response for CD4
<sup>+</sup> T cells and CD8
<sup>+</sup> T cells). Moreover, the Mn-LNPs, compared with commercial aluminum adjuvant, significantly
enhanced the antigen-specific IgG2b subclass response.
</p>
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<h5 class="section-title" id="d1449262e174">Conclusion:</h5>
<p dir="auto" id="d1449262e176">The Mn-LNP co-delivery system efficiently delivered both VZV antigen and CpG adjuvant,
and markedly improved the VZV vaccine-induced T cell response. Thus, this Mn-LNP co-delivery
system has promising potential in promoting VZV vaccine efficacy.
</p>
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| ISSN: | 2737-7466 2737-7474 |