Development of a Potent Stabilizer for Long-Term Storage of Foot-and-Mouth Disease Vaccine Antigens

Abstract

A local virus isolate, O/SKR/JC/2014 (O JC), has been considered as a candidate vaccine strain in the development of a domestic foot-and-mouth disease (FMD) vaccine in Korea. However, producing and preserving a sufficient quantity of intact vaccine antigens from the O JC strain was difficult owing to its distinctive structural instability compared to other candidate vaccine strains. Based on this feature, the O JC strain was adopted as a model virus for the stabilization study to determine the optimal stabilizer composition, which enables long-term storage of the FMD vaccine antigen in both aqueous and frozen phases. In contrast to O JC vaccine antigens stored in routinely used Tris-buffered or phosphate-buffered saline, those stored in Tris-KCl buffer showed extended shelf-life at both 4 °C and −70 °C. Additionally, the combined application of 10% sucrose and 5% lactalbumin hydrolysate could protect O JC 146S particles from massive structural breakdown in an aqueous state for up to one year. The stabilizer composition was also effective for other FMDV strains, including serotypes A and Asia 1. With this stabilizer composition, FMD vaccine antigens could be flexibly preserved during the general production process, pending status under refrigeration and banking under ultrafreezing.

Calcium Chloride as a Novel Stabilizer for Foot-and-Mouth Disease Virus and Its Application in the Vaccine Formulation

“…Likewise, the obvious instability of the type O Jincheon virus (SEA/Mya-98 lineage), a Korean isolate, was confirmed to be highly labile in our previous study [35]. To overcome this, we developed a stabilizing agent-SLA, which is a mixture of sucrose and lactalbumin hydrolysate (SLA) [35]. However, since this is a composition that can support the growth of microorganisms, it was found to be vulnerable to the growth of bacteria and fungi, even when stored at 4 • C, and it forms protein precipitates.…”

“…In particular, type O has been reported to have relatively lower stability than other FMDV serotypes [11,34]. Likewise, the obvious instability of the type O Jincheon virus (SEA/Mya-98 lineage), a Korean isolate, was confirmed to be highly labile in our previous study [35]. To overcome this, we developed a stabilizing agent-SLA, which is a mixture of sucrose and lactalbumin hydrolysate (SLA) [35].…”

Novel Capsid-Specific Single-Domain Antibodies with Broad Foot-and-Mouth Disease Strain Recognition Reveal Differences in Antigenicity of Virions, Empty Capsids, and Virus-Like Particles

“…The currently available capsid-specific VHHs M170F and M210F do not bind strain O/TAW/3/97 [23] nor O/BY/CHA/2010 (Figure 2). Here we could not isolate novel capsid-specific VHHs using strain O/TAW/3/97, which could be due to the low stability of strains from the serotype O lineage circulating in South East Asia [10]. The novel serotype Asia 1 capsid-specific VHH M658F had high sequence homology to the earlier isolated M332F [24].…”

“…Incubation of intact capsids at high temperatures or low pH leads to irreversible dissociation into 12S subunits, resulting in a strongly reduced immunogenicity [6][7][8]. Consequently, the 146S content of conventional vaccines and 75S content of VLP vaccines determines vaccine quality and should thus be monitored closely during vaccine manufacturing, formulation, and storage [9][10][11][12].…”

Cross-Serotype Reactivity of ELISAs Used to Detect Antibodies to the Structural Proteins of Foot-and-Mouth Disease Virus

“…The procedure for virus inactivation is often a critical step in antigen preparation as it cannot be done at refrigeration temperatures and may need to be carried out twice for safety reasons. Freezing and thawing antigens should be avoided and cryoprotectants can stabilize antigens for storage at sub-zero temperatures [ 34 , 35 , 36 ].…”