Abstract
Biologics can be combined with liquid polymer materials and electrospun to produce a dry nanofibrous scaffold. Unlike spray-drying and freeze-drying, electrospinning minimizes the physiological stress on sensitive materials, and nanofiber mat properties such as hydrophobicity, solubility, and melting temperature can be tuned based on the polymer composition. In this study, we explored the dry formulation of a virus-like particle (VLP) vaccine by electrospinning VLP derived from rabbit hemorrhagic disease virus modified to carry the MHC-I gp100 tumor-associated antigen epitope. VLP were added to a polyvinylpyrrolidone (PVP) solution (15% w/v) followed by electrospinning at 24 kV. Formation of a nanofibrous mat was confirmed by scanning electron microscopy, and the presence of VLP was confirmed by transmission electron microscopy and Western blot. VLP from the nanofibers induced T-cell activation and interferon- (IFN-) γ production in vitro. To confirm in vivo cytotoxicity, Pmel mice treated by injection with gp100 VLP from nanofibers induced a gp100 specific immune response, lysing approximately 65% of gp100-pulsed target cells, comparable to mice vaccinated with gp100 VLP in PBS. VLP from nanofibers also induced an antibody response. This work shows that electrospinning can be used to dry-formulate VLP, preserving both humoral and cell-mediated immunity.
Highlights
Virus-like particles (VLP) have been extensively explored as vaccine material, with current VLP vaccines comprising liquid suspensions
Results confirm that the 60 kDa protein was VP60 and that loading was relatively consistent across the mat. These results indicate that VLP can be electrospun into a dry nanofibrous mat and that intact VLP can be recovered upon dissolution of the mat
Results of the in vivo experiments demonstrate that VLP formulated in the nanofibers were able to stimulate a cell-mediated and humoral immune response without loss of functionality when compared to VLP that had not been incorporated into nanofibers
Summary
Virus-like particles (VLP) have been extensively explored as vaccine material, with current VLP vaccines comprising liquid suspensions. A broken cold chain could result in wasted vaccine stock or the administration of ineffective vaccines. This problem is often compounded in countries where cold chain infrastructures may be suboptimal [14]. One possible approach to minimize the reliance on cold-chain handling is to prepare a dry formulation of the vaccine material, which can be reconstituted into a liquid suspension prior to administration. Dry formulations are less prone to temperature-induced degradation, leading to reduced reliance on the cold chain, fewer wasted vaccine stocks, and an increase in cost-effectiveness and shelf life [16]
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