Abstract
Effective vaccine delivery and coverage to rural and resource-poor countries is hindered by the dependence on cold chain storage. As such, developments of cold chain-free technologies are highly sought. Although spray dried adenoviral vectors have shown long term stability at ambient temperatures and relatively low humidity, it remains to be determined whether similar excipient formulations are applicable to other viral vectors. To address this, we have spray dried vesicular stomatitis virus (VSV)-vectors with a panel of well-characterized sugar excipients to determine the optimal formulation for vector stabilization. Upon reconstitution, we show that trehalose conferred superior stability of VSV both in vitro and in vivo. Importantly, following cold chain-free storage at elevated temperatures at 37 °C for 15 days, we show that a VSV-vectored vaccine retains its in vivo immunogenicity, whereas a liquid control completely lost its immune-stimulating ability. Our results provide foundational evidence that spray drying with properly tested excipients can stabilize viral vectors such as VSV, allowing them to be stored long-term at elevated temperatures without dependency on cold chain conditions.
Highlights
Effective vaccine delivery and coverage to rural and resource-poor countries is hindered by the dependence on cold chain storage
Through spray drying of the model vesicular stomatitis virus (VSV) vector expressing green fluorescent protein (VSVGFP), we have identified excipients that minimize the loss of viral activity resulting from the spray drying process
We first sought to profile excipients that best stabilize VSV by utilizing an in vitro endpoint dilution assay to assess the infectivity of a VSV vector expressing Green Fluorescent Protein (GFP) (VSVGFP); stability trends found with the excipients for the viral vector are expected to be reflected with VSVAg85A but the scope of the in vitro studies would have been severely limited without the relatively rapid quantification of viral activity based on detection of a fluorescent response
Summary
Effective vaccine delivery and coverage to rural and resource-poor countries is hindered by the dependence on cold chain storage. Our results provide foundational evidence that spray drying with properly tested excipients can stabilize viral vectors such as VSV, allowing them to be stored long-term at elevated temperatures without dependency on cold chain conditions. To mitigate the need for cold chain storage of liquid vaccines, research continues to be directed towards developing thermally stable vaccines, through the vitrification of excipients encapsulating these biologics into glassy powders[8]. This stability does not eliminate the need for cooler transport/storage conditions, especially in hot climates, but eases the technology demands and extends the length of time that the cold chain can be broken before the vaccine needs to be discarded. The spray drying of powdered vaccines against measles, tuberculosis, hepatitis B, and influenza for example, has been explored with demonstrated improvements in t hermostability[9,13,14,15]
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