Physiochemical Changes to TTCF Ensilication Investigated Using Time-Resolved SAXS

Aswin Doekhie,Asel Sartbaeva,Yun-Chu Chen,Jean M H Van Den Elsen,Francoise Koumanov,Rajeev Dattani,Karen J Edler

doi:10.3390/appliedchem1010002

Aswin Doekhie, Asel Sartbaeva + Show 5 more

Open Access

https://doi.org/10.3390/appliedchem1010002

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Abstract

Successful eradication or control of prevailing infectious diseases is linked to vaccine efficacy, stability, and distribution. The majority of protein-based vaccines are transported at fridge (2–8 °C) temperatures, cold chain, to retain potency. However, this has been shown to be problematic. Proteins are inherently susceptible to thermal fluctuations, occurring during transportation, causing them to denature. This leads to ineffective vaccines and an increase in vaccine-preventable diseases, especially in low-income countries. Our research utilises silica to preserve vaccines at room temperature, removing the need for cold chain logistics. The methodology is based upon sol–gel chemistry in which soluble silica is employed to encapsulate and ensilicate vaccine proteins. This yields a protein-loaded silica nanoparticle powder which is stored at room temperature and subsequently released using a fast chemical process. We have previously shown that tetanus toxin C fragment (TTCF) ensilication is a diffusion-limited cluster aggregation (DLCA)-based process using time-resolved small-angle x-ray scattering (SAXS). Here, we present our expanded investigation on the modularity of this system to further the understanding of ensilication via time-resolved SAXS. Our results show that variations in the ensilication process could prove useful in the transition from batch to in-flow manufacturing of ensilicated nanoparticles.

Highlights

There is an urgent demand for thermostable vaccines [1,2]
Our results show that variations in the ensilication process could prove useful in the transition from batch to in-flow manufacturing of ensilicated nanoparticles
There, we found that ensilication is a three-staged diffusion-limited cluster aggregation process (DLCA [21]) with each stage transitioning relatively rapidly, in order of seconds to minutes (Figure 1)

Summary

Introduction

There is an urgent demand for thermostable vaccines [1,2]. Most of the adjuvantbased protein vaccines are liquid formulated and have to be transported via the cold chain infrastructure. It allows for problems to occur at any stage [3,4,5,6,7]. To minimise the dependency on the cold chain, we have to enable room temperature stable vaccines. There have been many attempts to stabilise vaccines, and there are several strategies being explored [8,9,10,11,12,13,14,15,16]

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Conclusion