Development of Long-Term Stability of Enveloped rVSV Viral Vector Expressing SARS-CoV-2 Antigen Using a DOE-Guided...

Area of Science:

• Vaccinology
• Biotechnology
• Virology

Background:

• Liquid formulations offer advantages over lyophilized vaccines, including cost-effectiveness and ease of manufacturing and distribution.
• However, enveloped viral vector vaccines in liquid form often lack long-term stability.
• This study addresses the stability challenge for enveloped viral vector vaccines, specifically a recombinant Vesicular Stomatitis Virus (VSV) expressing the SARS-CoV-2 spike glycoprotein.

Purpose of the Study:

• To develop and optimize stable liquid formulations for an enveloped recombinant VSV-SARS-CoV-2 vaccine.
• To identify critical factors influencing viral vector stability under various stress conditions.
• To establish optimal long-term storage conditions for the liquid vaccine formulation.

Main Methods:

• Utilized a Design of Experiments (DOE) approach to efficiently assess viral vector stability dynamics.
• Conducted initial stability studies to identify key excipients (trehalose, gelatin, histidine) and stress conditions (freeze-thaw, varying temperatures).
• Implemented DOE with accelerated stress conditions (37 °C) to identify optimal formulations and guide long-term storage evaluations.

Main Results:

• Trehalose, gelatin, and histidine were found to maintain functional viral titers during freeze-thaw and temperature stress.
• DOE analysis identified optimal liquid formulations under accelerated stress conditions.
• Several formulations containing sugars (sucrose, trehalose, sorbitol), gelatin, and histidine buffer demonstrated improved stability of rVSV-SARS-CoV-2 at 4 °C for six months.

Conclusions:

• This research presents an effective strategy for developing stable liquid formulations for enveloped viral vector vaccines.
• The optimized formulations enhance the thermostability of rVSV-SARS-CoV-2, crucial for vaccine efficacy.
• The findings contribute valuable knowledge to the field of enveloped viral vector vaccine development and storage.