Manganese-coordinated lipid nanoparticles boost VZV vaccine-induced T cell responses

Announcing a new article publication for Zoonoses journal. 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.

To achieve favorable VZV antigen and adjuvant utilization efficiency, a co-delivery system was constructed 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. Mn-LNP size and morphology were characterised through transmission electron microscopy and quantified the manganese on palmitic acid-Mn through X-ray photoelectron spectroscopy. The performance of the Mn-LNP co-delivery system in enhancing VZV vaccine-induced immune responses was evaluated in a mouse model.

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 aluminium adjuvant, significantly enhanced VZV gE antigen-specific CD4⁺ and CD8⁺ T cell responses (1.47-fold and 5.66-fold enhanced IFN-γ response for CD4⁺ T cells and CD8⁺ T cells; 2.25-fold and 2.64-fold enhanced TNF-α response for CD4⁺ T cells and CD8⁺ T cells; and 2.62-fold and 3.17-fold enhanced IL-2 response for CD4⁺ T cells and CD8⁺ T cells). Moreover, the Mn-LNPs, compared with commercial aluminium adjuvant, significantly enhanced the antigen-specific IgG2b subclass response.

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.