Investigation of the Optimal Medium and Application Strategy for Foot‐and‐mouth Disease Vaccine Antigen Production

2021 ◽  
Author(s):  
Ah‐Young Kim ◽  
Hyejin Kim ◽  
Sun Young Park ◽  
Sang Hyun Park ◽  
Jung‐Min Lee ◽  
...  
Keyword(s):  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Vaccine Antigen ◽  
Antigen Production ◽  
Foot And Mouth ◽  
Optimal Medium

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

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 252
Author(s):  
Ah-Young Kim ◽  
Hyejin Kim ◽  
Sun Young Park ◽  
Sang Hyun Park ◽  
Jae-Seok Kim ◽  
...  
Keyword(s):  
Foot And Mouth Disease ◽  
Structural Instability ◽  
Mouth Disease ◽  
Candidate Vaccine ◽  
Vaccine Antigen ◽  
Long Term Storage ◽  
Vaccine Antigens ◽  
Foot And Mouth ◽  
Term Storage

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.

scholarly journals Production of a Foot-and-Mouth Disease Vaccine Antigen Using Suspension-Adapted BHK-21 Cells in a Bioreactor

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 505
Author(s):  
Soon-Yong Park ◽  
Ji-Yul Kim ◽  
Kyoung-Hwa Ryu ◽  
Ah-Young Kim ◽  
Jae-Mun Kim ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Density ◽  
Virus Titer ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Vaccine Antigen ◽  
Vaccine Production ◽  
Serum Free ◽  
Fmd Virus ◽  
Foot And Mouth

The baby hamster kidney-21 (BHK-21) cell line is a continuous cell line used to propagate foot-and-mouth disease (FMD) virus for vaccine manufacturing. BHK-21 cells are anchorage-dependent, although suspension cultures would enable rapid growth in bioreactors, large-scale virus propagation, and cost-effective vaccine production with serum-free medium. Here, we report the successful adaptation of adherent BHK-21 cells to growth in suspension to a viable cell density of 7.65 × 106 cells/mL on day 3 in serum-free culture medium. The suspension-adapted BHK-21 cells showed lower adhesion to five types of extracellular matrix proteins than adherent BHK-21 cells, which contributed to the suspension culture. In addition, a chemically defined medium (selected by screening various prototype media) led to increased FMD virus production yields in the batch culture, even at a cell density of only 3.5 × 106 cells/mL. The suspension BHK-21 cell culture could be expanded to a 200 L bioreactor from a 20 mL flask, which resulted in a comparable FMD virus titer. This platform technology improved virus productivity, indicating its potential for enhancing FMD vaccine production.

scholarly journals Application of Heparin Affinity Chromatography to Produce a Differential Vaccine without Eliciting Antibodies against the Nonstructural Proteins of the Serotype O Foot-and-Mouth Disease Viruses

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1405
Author(s):  
Sun Young Park ◽  
Jung-Min Lee ◽  
Ah-Young Kim ◽  
Sang Hyun Park ◽  
Jae-Seok Kim ◽  
...  
Keyword(s):  
Affinity Chromatography ◽  
Neutralizing Antibodies ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Vaccine Antigen ◽  
Nonstructural Proteins ◽  
Serotype O ◽  
Intact Virus ◽  
Foot And Mouth ◽  
Heparin Affinity

Although polyethylene glycol (PEG) application is the most widely used method in removing nonstructural proteins (NSPs) for foot-and-mouth disease (FMD) vaccine production, some NSPs remaining in the antigen could elicit antibodies against these proteins after repeated vaccinations in livestock. Therefore, the purpose of this study was to purify the FMD virus (FMDV) via affinity chromatography using a heparin ligand to remove most proteins, including NSPs. Chromatography showed an intact virus (146S) particle recovery of 70% or more for three different strains of serotype O FMDV (two locally isolated strains and one genetically modified strain). The experimental vaccine made with antigens eluted via heparin affinity chromatography elicited virus-neutralizing antibodies against homologous viruses but did not induce antibodies against NSPs even after five immunizations in goats; this indicated that the NSPs were effectively removed from the vaccine antigen. This method can then be used to produce a higher-quality vaccine compared with PEG application in terms of the purity of the FMD vaccine. Therefore, this result would be an important groundwork for advanced FMD vaccine manufacturing in the near future.

scholarly journals Structures of Coxsackievirus A16 Capsids with Native Antigenicity: Implications for Particle Expansion, Receptor Binding, and Immunogenicity

2015 ◽  
Vol 89 (20) ◽  
pp. 10500-10511 ◽  
Author(s):  
Jingshan Ren ◽  
Xiangxi Wang ◽  
Ling Zhu ◽  
Zhongyu Hu ◽  
Qiang Gao ◽  
...  
Keyword(s):  
High Resolution ◽  
Insect Cells ◽  
Vaccine Development ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Vaccine Antigen ◽  
Coxsackievirus A16 ◽  
Structure Based Drug Design ◽  
Foot And Mouth

ABSTRACTEnterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the primary causes of the epidemics of hand-foot-and-mouth disease (HFMD) that affect more than a million children in China each year and lead to hundreds of deaths. Although there has been progress with vaccines for EV71, the development of a CVA16 vaccine has proved more challenging, and the EV71 vaccine does not give useful cross-protection, despite the capsid proteins of the two viruses sharing about 80% sequence identity. The structural details of the expanded forms of the capsids, which possess nonnative antigenicity, are now well understood, but high resolution information for the native antigenic form of CVA16 has been missing. Here, we remedy this with high resolution X-ray structures of both mature and natural empty CVA16 particles and also of empty recombinant viruslike particles of CVA16 produced in insect cells, a potential vaccine antigen. All three structures are unexpanded native particles and antigenically identical. The recombinant particles have recruited a lipid moiety to stabilize the native antigenic state that is different from the one used in a natural virus infection. As expected, the mature CVA16 virus is similar to EV71; however, structural and immunogenic comparisons highlight differences that may have implications for vaccine production.IMPORTANCEHand-foot-and-mouth disease is a serious public health threat to children in Asian-Pacific countries, resulting in millions of cases. EV71 and CVA16 are the two dominant causative agents of the disease that, while usually mild, can cause severe neurological complications, leading to hundreds of deaths. EV71 vaccines do not provide protection against CVA16. A CVA16 vaccine or bivalent EV71/CVA16 vaccine is therefore urgently needed. We report atomic structures for the mature CVA16 virus, a natural empty particle, and a recombinant CVA16 virus-like particle that does not contain the viral genome. All three particles have similar structures and identical antigenicity. The recombinant particles, produced in insect cells (a system suitable for making vaccine antigen), are stabilized by recruiting from the insect cells a small molecule that is different from that used by the virus in a normal infection. We present structural and immunogenic comparisons with EV71 to facilitate structure-based drug design and vaccine development.

scholarly journals Efficacy of SAT2 Foot-and-Mouth Disease Vaccines Formulated with Montanide ISA 206B and Quil-A Saponin Adjuvants

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 996
Author(s):  
Ntungufhadzeni M. Rathogwa ◽  
Katherine A. Scott ◽  
Pamela Opperman ◽  
Jacques Theron ◽  
Francois F. Maree
Keyword(s):  
Antibody Response ◽  
Foot And Mouth Disease ◽  
Neutralizing Antibody ◽  
Mouth Disease ◽  
Antigenic Drift ◽  
Cold Chain ◽  
Vaccine Antigen ◽  
Effective Control ◽  
Adjuvanted Vaccine ◽  
Foot And Mouth

The effective control of foot-and-mouth disease (FMD) relies strongly on the separation of susceptible and infected livestock or susceptible livestock and persistently infected wildlife, vaccination, and veterinary sanitary measures. Vaccines affording protection against multiple serotypes for longer than six months and that are less reliant on the cold chain during handling are urgently needed for the effective control of FMD in endemic regions. Although much effort has been devoted to improving the immune responses elicited through the use of modern adjuvants, their efficacy is dependent on the formulation recipe, target species and administration route. Here we compared and evaluated the efficacy of two adjuvant formulations in combination with a structurally stabilized SAT2 vaccine antigen, designed to have improved thermostability, antigen shelf-life and longevity of antibody response. Protection mediated by the Montanide ISA 206B-adjuvanted or Quil-A Saponin-adjuvanted SAT2 vaccines were comparable. The Montanide ISA 206B-adjuvanted vaccine elicited a higher SAT2 neutralizing antibody response and three times higher levels of systemic IFN-γ responses at 14- and 28-days post-vaccination (dpv) were observed compared to the Quil-A Saponin-adjuvanted vaccine group. Interestingly, serum antibodies from the immunized animals reacted similarly to the parental vaccine virus and viruses containing mutations in the VP2 protein that simulate antigenic drift in nature.

scholarly journals Modelling the Influence of Foot-and-Mouth Disease Vaccine Antigen Stability and Dose on the Bovine Immune Response

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e30435 ◽  
Author(s):  
David Schley ◽  
Reiko J. Tanaka ◽  
Kritsada Leungchavaphongse ◽  
Vahid Shahrezaei ◽  
John Ward ◽  
...  
Keyword(s):  
Immune Response ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Vaccine Antigen ◽  
Foot And Mouth

Biophysical Measurement of Molecular Weight of Foot-and-Mouth Disease RNA Fragments

1974 ◽  
Vol 32 ◽  
pp. 262-263
Author(s):  
Sydney S. Breese ◽  
Howard L. Bachrach
Keyword(s):  
Chemical Properties ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Distilled Water ◽  
Bovine Plasma ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Carbon Coated ◽  
Rna Fragments ◽  
Physical And Chemical

Continuing studies on the physical and chemical properties of foot-and-mouth disease virus (FMDV) have included electron microscopy of RNA strands released when highly purified virus (1) was dialyzed against demlneralized distilled water. The RNA strands were dried on formvar-carbon coated electron microscope screens pretreated with 0.1% bovine plasma albumin in distilled water. At this low salt concentration the RNA strands were extended and were stained with 1% phosphotungstic acid. Random dispersions of strands were recorded on electron micrographs, enlarged to 30,000 or 40,000 X and the lengths measured with a map-measuring wheel. Figure 1 is a typical micrograph and Fig. 2 shows the distributions of strand lengths for the three major types of FMDV (A119 of 6/9/72; C3-Rezende of 1/5/73; and O1-Brugge of 8/24/73.

High resolution surface structure of foot-and-mouth disease virus

1978 ◽  
Vol 36 (2) ◽  
pp. 376-377
Author(s):  
S. S. Breese ◽  
H. L. Bachrach
Keyword(s):  
Electron Microscopy ◽  
High Resolution ◽  
Surface Structure ◽  
Disease Virus ◽  
Potassium Phosphate ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Physical Measurements ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Models for the structure of foot-and-mouth disease virus (FMDV) have been proposed from chemical and physical measurements (Brown, et al., 1970; Talbot and Brown, 1972; Strohmaier and Adam, 1976) and from rotational image-enhancement electron microscopy (Breese, et al., 1965). In this report we examine the surface structure of FMDV particles by high resolution electron microscopy and compare it with that of particles in which the outermost capsid protein VP3 (ca. 30, 000 daltons) has been split into smaller segments, two of which VP3a and VP3b have molecular weights of about 15, 000 daltons (Bachrach, et al., 1975).Highly purified and concentrated type A12, strain 119 FMDV (5 mg/ml) was prepared as previously described (Bachrach, et al., 1964) and stored at 4°C in 0. 2 M KC1-0. 5 M potassium phosphate buffer at pH 7. 5. For electron microscopy, 1. 0 ml samples of purified virus and trypsin-treated virus were dialyzed at 4°C against 0. 2 M NH4OAC at pH 7. 3, deposited onto carbonized formvar-coated copper screens and stained with phosphotungstic acid, pH 7. 3.

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