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11 pages, 3127 KiB

Open AccessArticle

Effect of Foot-and-Mouth Disease Virus 2B Viroporin on Expression and Extraction of Mammalian Cell Culture Produced Foot-and-Mouth Disease Virus-like Particles

by Victoria Primavera, Janine Simmons, Benjamin A. Clark, John G. Neilan and Michael Puckette

Vaccines 2022, 10(9), 1506; https://doi.org/10.3390/vaccines10091506 - 9 Sep 2022

Cited by 2 | Viewed by 2117

Abstract

To improve the production of foot-and-mouth disease (FMD) molecular vaccines, we sought to understand the effects of the FMD virus (FMDV) 2B viroporin in an experimental, plasmid-based, virus-like particle (VLP) vaccine. Inclusion of the FMDV viroporin 2B into the human Adenovirus 5 vectored [...] Read more.

To improve the production of foot-and-mouth disease (FMD) molecular vaccines, we sought to understand the effects of the FMD virus (FMDV) 2B viroporin in an experimental, plasmid-based, virus-like particle (VLP) vaccine. Inclusion of the FMDV viroporin 2B into the human Adenovirus 5 vectored FMD vaccine enhanced transgene expression despite independent 2B expression negatively affecting cell viability. Evaluating both wildtype 2B and mutants with disrupted viroporin activity, we confirmed that viroporin activity is detrimental to overall transgene expression when expressed independently. However, the incorporation of 2B into an FMD molecular vaccine construct containing a wildtype FMDV 3C protease, a viral encoded protease responsible for processing structural proteins, resulted in enhancement of transgene expression, validating previous observations. This benefit to transgene expression was negated when using the FMDV 3C^L127P mutant, which has reduced processing of host cellular proteins, a reversion resulting from 2B viroporin activity. Inclusion of 2B into VLP production constructs also adversely impacted antigen extraction, a possible side effect of 2B-dependent rearrangement of cellular membranes. These results demonstrate that inclusion of 2B enhanced transgene expression when a wildtype 3C protease is present but was detrimental to transgene expression with the 3C^L127P mutant. This has implications for future molecular FMD vaccine constructs, which may utilize mutant FMDV 3C proteases. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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9 pages, 3017 KiB

Open AccessArticle

Factors Involved in Removing the Non-Structural Protein of Foot-and-Mouth Disease Virus by Chloroform and Scale-Up Production of High-Purity Vaccine Antigens

by Sun Young Park, Sim-In Lee, Jong Sook Jin, Eun-Sol Kim, Jae Young Kim, Ah-Young Kim, Sang Hyun Park, Jung-Won Park, Soonyong Park, Eun Gyo Lee, Jong-Hyeon Park, Young-Joon Ko and Choi-Kyu Park

Vaccines 2022, 10(7), 1018; https://doi.org/10.3390/vaccines10071018 - 24 Jun 2022

Cited by 3 | Viewed by 2292

Abstract

Foot-and-mouth disease (FMD) is an economically important and highly infectious viral disease, predominantly controlled by vaccination. The removal of non-structural proteins (NSPs) is very important in the process of FMD vaccine production, because vaccinated and naturally infected animals can be distinguished by the [...] Read more.

Foot-and-mouth disease (FMD) is an economically important and highly infectious viral disease, predominantly controlled by vaccination. The removal of non-structural proteins (NSPs) is very important in the process of FMD vaccine production, because vaccinated and naturally infected animals can be distinguished by the presence of NSP antibodies in the FMD serological surveillance. A previous study reported that 3AB protein, a representative of NSPs, was removed by chloroform treatment. Therefore, in this study, the causes of 3AB removal and factors affecting the effect of chloroform were investigated. As a result, the effectiveness of chloroform differed depending on the virus production medium and was eliminated by detergents. In addition, it was found that 3AB protein removal by chloroform is due to the transmembrane domain of the N-terminal region (59–76 amino acid domain). Further, industrial applicability was verified by applying the chloroform treatment process to scale-up FMD vaccine antigen production. A novel downstream process using ultrafiltration instead of polyethylene glycol precipitation for high-purity FMD vaccine antigen production was established. This result will contribute toward simplifying the conventional process of manufacturing FMD vaccine antigens and ultimately reducing the time and cost of vaccine production. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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17 pages, 4166 KiB

Open AccessArticle

Comparison of High-Performance Liquid Chromatography with Sucrose Density Gradient Ultracentrifugation for the Quantification of Foot-and-Mouth Disease Vaccine Antigens

by Ah-Young Kim, Sun Young Park, Sang Hyun Park, Jae Young Kim, Jong Sook Jin, Eun-Sol Kim, Jong-Hyeon Park and Young-Joon Ko

Vaccines 2022, 10(5), 667; https://doi.org/10.3390/vaccines10050667 - 22 Apr 2022

Cited by 2 | Viewed by 2543

Abstract

Foot-and-mouth disease (FMD) causes substantial economic losses in the livestock industry. The protective immunizing component of the FMD virus (FMDV) is a ribonucleoprotein particle with a sedimentation coefficient of 146S. Size-exclusion high-performance liquid chromatography (SE-HPLC) was introduced to replace sucrose density gradient ultracentrifugation [...] Read more.

Foot-and-mouth disease (FMD) causes substantial economic losses in the livestock industry. The protective immunizing component of the FMD virus (FMDV) is a ribonucleoprotein particle with a sedimentation coefficient of 146S. Size-exclusion high-performance liquid chromatography (SE-HPLC) was introduced to replace sucrose density gradient ultracentrifugation (SDG), which is the gold standard for the quantification of FMDV 146S particles. SE-HPLC showed a pattern similar to that of SDG; however, the two methods resulted in different quantities for the same amount of 146S particles. This study aimed to identify the reason for this disparity and adjust the difference between the two methods by employing a standard material. While SE-HPLC displayed all the virus particles in the peak fraction by SDS-PAGE and Western blotting, the virus particles were widely dispersed in multiple fractions, including peak fractions in the SDG. To adjust the difference between the two methods, a stable surrogate virus, bovine enterovirus, was devised to draw a standard curve, and the gap was reduced to <10%. To our knowledge, this is the first report to provide experimental evidence on the difference between SDG and SE-HPLC for the quantification of FMDV particles. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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15 pages, 2100 KiB

Open AccessArticle

Validation of Pretreatment Methods for the In-Process Quantification of Foot-and-Mouth Disease Vaccine Antigens

by Ah-Young Kim, Sun Young Park, Sang Hyun Park, Jong Sook Jin, Eun-Sol Kim, Jae Young Kim, Jong-Hyeon Park and Young-Joon Ko

Vaccines 2021, 9(11), 1361; https://doi.org/10.3390/vaccines9111361 - 19 Nov 2021

Cited by 3 | Viewed by 2994

Abstract

Foot-and-mouth disease (FMD), caused by the FMD virus (FMDV), is controlled by vaccine policy in many countries. For vaccine potency, the content of intact virus particles (146S antigens) is critical, and the sucrose density gradient (SDG) fractionation is the gold standard for the [...] Read more.

Foot-and-mouth disease (FMD), caused by the FMD virus (FMDV), is controlled by vaccine policy in many countries. For vaccine potency, the content of intact virus particles (146S antigens) is critical, and the sucrose density gradient (SDG) fractionation is the gold standard for the quantification of 146S antigens. However, this method has several drawbacks. Although size-exclusion high-performance liquid chromatography (SE-HPLC) was introduced to replace the classic method, its application is generally confined to purified samples owing to the interfering signals. Therefore, we aimed to develop optimal pretreatment methods for SE-HPLC quantification in less purified samples. Crude virus infection supernatant (CVIS) and semi-purified samples with PEG precipitation (PEG-P) were used. Chloroform pretreatment was essential to remove a high level of non-specific signals in CVIS, whereas it caused loss of 146S antigens without the distinctive removal of non-specific signals in PEG-P. Benzonase pretreatment was required to improve the resolution of the target peak in the chromatogram for both CVIS and PEG-P. Through spiking tests with pure 146S antigens, it was verified that the combined pretreatment with chloroform and benzonase was optimal for the CVIS, while the sole pretreatment of benzonase was beneficial for PEG-P. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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11 pages, 1839 KiB

Open AccessArticle

Emergency FMD Serotype O Vaccines Protect Cattle against Heterologous Challenge with a Variant Foot-and-Mouth Disease Virus from the O/ME-SA/Ind2001 Lineage

by Nagendrakumar Balasubramanian Singanallur, Aldo Dekker, Phaedra Lydia Eblé, Froukje van Hemert-Kluitenberg, Klaas Weerdmeester, Jacquelyn J Horsington and Wilna Vosloo

Vaccines 2021, 9(10), 1110; https://doi.org/10.3390/vaccines9101110 - 29 Sep 2021

Cited by 7 | Viewed by 2656

Abstract

Vaccination is one of the best approaches to control and eradicate foot-and-mouth disease (FMD). To achieve this goal, vaccines with inactivated FMD virus antigen in suitable adjuvants are being used in addition to other control measures. However, only a limited number of vaccine [...] Read more.

Vaccination is one of the best approaches to control and eradicate foot-and-mouth disease (FMD). To achieve this goal, vaccines with inactivated FMD virus antigen in suitable adjuvants are being used in addition to other control measures. However, only a limited number of vaccine strains are commercially available, which often have a restricted spectrum of activity against the different FMD virus strains in circulation. As a result, when new strains emerge, it is important to measure the efficacy of the current vaccine strains against these new variants. This is important for countries where FMD is endemic but also for countries that hold an FMD vaccine bank, to ensure they are prepared for emergency vaccination. The emergence and spread of the O/ME-SA/Ind-2001 lineage of viruses posed a serious threat to countries with OIE-endorsed FMD control plans who had not reported FMD for many years. In vitro vaccine-matching results showed a poor match (r₁-value < 0.3) with the more widely used vaccine strain O₁ Manisa and less protection in a challenge test. This paper describes the use of the O3039 vaccine strain as an alternative, either alone or in combination with the O₁ Manisa vaccine strain with virulent challenge by a O/ME-SA/Ind-2001d sub-lineage virus from Algeria (O/ALG/3/2014). The experiment included challenge at 7 days post-vaccination (to study protection and emergency use) and 21 days post-vaccination (as in standard potency studies). The results indicated that the O3039 vaccine strain alone, as well as the combination with O₁ Manisa, is effective against this strain of the O/ME-SA/Ind/2001d lineage, offering protection from clinical disease even after 7 days post-vaccination with a reduction in viraemia and virus excretion. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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11 pages, 1386 KiB

Open AccessCommunication

The Potential Adjuvanticity of CAvant^®SOE for Foot-and-Mouth Disease Vaccine

by Young-Hoon Ahn, W. A. Gayan Chathuranga, Young-Jung Shim, D. K. Haluwana, Eun-Hee Kim, In-Joong Yoon, Yong-Taik Lim, Sung Ho Shin, Hyundong Jo, Seong Yun Hwang, Hyun Mi Kim, Min Ja Lee, Jong-Hyeon Park, Sung-Sik Yoo and Jong-Soo Lee

Vaccines 2021, 9(10), 1091; https://doi.org/10.3390/vaccines9101091 - 28 Sep 2021

Cited by 5 | Viewed by 4234

Abstract

Foot-and-mouth disease (FMD) is a notifiable contagious disease of cloven-hoofed mammals. A high potency vaccine that stimulates the host immune response is the foremost strategy used to prevent disease persistence in endemic regions. FMD vaccines comprise inactivated virus antigens whose immunogenicity is potentiated [...] Read more.

Foot-and-mouth disease (FMD) is a notifiable contagious disease of cloven-hoofed mammals. A high potency vaccine that stimulates the host immune response is the foremost strategy used to prevent disease persistence in endemic regions. FMD vaccines comprise inactivated virus antigens whose immunogenicity is potentiated by immunogenic adjuvants. Oil-based adjuvants have clear advantages over traditional adjuvant vaccines; however, there is potential to develop novel adjuvants to increase the potency of FMD vaccines. Thus, we aimed to evaluate the efficacy of a novel water-in-oil emulsion, called CAvant^®SOE, as a novel vaccine adjuvant for use with inactivated FMD vaccines. In this study, we found that inactivated A22 Iraq virus plus CAvant^®SOE (iA22 Iraq-CAvant^®SOE) induced effective antigen-specific humoral (IgG, IgG1, and IgG2a) and cell-mediated immune responses (IFN-γ and IL-4) in mice. Immunization of pigs with a single dose of iA22 Iraq-CAvant^®SOE also elicited effective protection, with no detectable clinical symptoms against challenge with heterologous A/SKR/GP/2018 FMDV. Levels of protection are strongly in line with vaccine-induced neutralizing antibody titers. Collectively, these results indicate that CAvant^®SOE-adjuvanted vaccine is a promising candidate for control of FMD in pigs. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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16 pages, 1772 KiB

Open AccessArticle

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

by Ntungufhadzeni M. Rathogwa, Katherine A. Scott, Pamela Opperman, Jacques Theron and Francois F. Maree

Vaccines 2021, 9(9), 996; https://doi.org/10.3390/vaccines9090996 - 7 Sep 2021

Cited by 7 | Viewed by 3076

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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15 pages, 14970 KiB

Open AccessArticle

Four Simple Biomimetic Mineralization Methods to Improve the Thermostability and Immunogenicity of Virus-like Particles as a Vaccine against Foot-and-Mouth Disease

by Mengnan Guo, Jiajun Li, Zhidong Teng, Mei Ren, Hu Dong, Yun Zhang, Jiaxi Ru, Ping Du, Shiqi Sun and Huichen Guo

Vaccines 2021, 9(8), 891; https://doi.org/10.3390/vaccines9080891 - 12 Aug 2021

Cited by 9 | Viewed by 2963

Abstract

The need for a cold chain system during storage and transport substantially increases the cost of vaccines. Virus-like particles (VLPs) are among the best countermeasures against foot and mouth disease virus (FMDV). However, VLPs are composed of pure proteins, and thus, are susceptible [...] Read more.

The need for a cold chain system during storage and transport substantially increases the cost of vaccines. Virus-like particles (VLPs) are among the best countermeasures against foot and mouth disease virus (FMDV). However, VLPs are composed of pure proteins, and thus, are susceptible to heat. To address this problem, four simple biomimetic mineralization methods with the use of calcium phosphate were developed to improve heat tolerance via biomineralization. The results showed that biomineralization can significantly improve the heat resistance of VLPs. The biomineralized VLPs can be stored at low as 25 °C for eight days, and 37 °C for four days. Animal experiments showed that biomineralization had no effect on the immunogenicity of VLPs or the expression of specific antibodies (Abs) and neutralizing Abs. Even after heat treatment at 37 °C for four days, the biomineralized VLPs remained immunogenic and produced highly specific and neutralizing Abs with a high rate of protection. These results suggest that these biomineralization approaches can promote the thermal stability of VLPs against and significantly reduce dependence on cold storage and delivery systems. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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20 pages, 2919 KiB

Open AccessArticle

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

by Haozhou Li, Aldo Dekker, Shiqi Sun, Alison Burman, Jeroen Kortekaas and Michiel M. Harmsen

Vaccines 2021, 9(6), 620; https://doi.org/10.3390/vaccines9060620 - 8 Jun 2021

Cited by 8 | Viewed by 3314

Abstract

Foot-and-mouth disease (FMD) vaccine efficacy is mainly determined by the content of intact virions (146S) and empty capsids (75S). Both particles may dissociate into 12S subunits upon vaccine manufacturing, formulation, and storage, reducing vaccine potency. We report the isolation of capsid-specific llama single-domain [...] Read more.

Foot-and-mouth disease (FMD) vaccine efficacy is mainly determined by the content of intact virions (146S) and empty capsids (75S). Both particles may dissociate into 12S subunits upon vaccine manufacturing, formulation, and storage, reducing vaccine potency. We report the isolation of capsid-specific llama single-domain antibodies (VHHs) with broad strain recognition that can be used to quantify intact capsids in FMD vaccines by double antibody sandwich (DAS) ELISA. One capsid-specific VHH displayed remarkably broad strain reactivity, recognizing 14 strains representing the 13 most important lineages of serotype A, and two VHHs cross-reacted with other serotypes. We additionally show that the newly isolated VHHs, as well as previously characterized VHHs, can be used to identify antigenic differences between authentic 146S and 75S capsids, as well as corresponding genetically engineered virus-like particles (VLPs). Our work underscores that VHHs are excellent tools for monitoring the quantity and stability of intact capsids during vaccine manufacturing, formulation, and storage, and additionally shows that VHHs can be used to predict the native-like structure of VLPs. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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13 pages, 1765 KiB

Open AccessArticle

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

by Soonyong Park, Ji Yul Kim, Kyoung-Hwa Ryu, Ah-Young Kim, Jaemun Kim, Young-Joon Ko and Eun Gyo Lee

Vaccines 2021, 9(5), 505; https://doi.org/10.3390/vaccines9050505 - 13 May 2021

Cited by 13 | Viewed by 6204

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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9 pages, 2126 KiB

Open AccessArticle

Effect of Foot-and-Mouth Disease Vaccination on Acute Phase Immune Response and Anovulation in Hanwoo (Bos taurus coreanae)

by Daehyun Kim, Joonho Moon, Jaejung Ha, Doyoon Kim and Junkoo Yi

Vaccines 2021, 9(5), 419; https://doi.org/10.3390/vaccines9050419 - 22 Apr 2021

Cited by 7 | Viewed by 2957

Abstract

Vaccination against foot-and-mouth disease is the most common method for preventing the spread of the disease; the negative effects include miscarriage, early embryo death, lower milk production, and decreased growth of fattening cattle. Therefore, in this study, we analyze the side effects of [...] Read more.

Vaccination against foot-and-mouth disease is the most common method for preventing the spread of the disease; the negative effects include miscarriage, early embryo death, lower milk production, and decreased growth of fattening cattle. Therefore, in this study, we analyze the side effects of vaccination by determining the acute immune response and ovulation rate after vaccinating cows for foot-and-mouth disease. The test axis was synchronized with ovulation using 100 Hanwoo (Bos taurus coreanae) cows from the Gyeongsangbuk-do Livestock Research Institute; only individuals with estrus confirmed by ovarian ultrasound were used for the test. All test axes were artificially inseminated 21 days after the previous estrus date. The control group was administered 0.9% normal saline, the negative control was injected intramuscularly with lipopolysaccharide (LPS; 0.5 µg/kg), and the test group was administered a foot-and-mouth disease virus vaccine (FMDV vaccine; bioaftogen, O and A serotypes, inactivated vaccine) 2, 9, and 16 days before artificial insemination. White blood cells and neutrophils increased significantly 1 day after vaccination, and body temperature in the rumen increased for 16 h after vaccination. Ovulation was detected 1 day after artificial fertilization by ovarian ultrasound. The ovulation rates were as follows: control 89%, LPS 60%, FMDV vaccine (−2 d) 50%, FMDV vaccine (−9 d) 75%, and FMDV vaccine (−16 d) 75%. In particular, the FMDV vaccine (−2 d) test group confirmed that ovulation was delayed for 4 days after artificial insemination. In addition, it was confirmed that it took 9 days after inoculation for the plasma contents of haptoglobin and serum amyloid A to recover to the normal range as the main acute immune response factors. The conception rate of the FMDV vaccine (−2 d) group was 20%, which was significantly lower than that of the other test groups. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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10 pages, 2150 KiB

Open AccessArticle

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

by Ah-Young Kim, Hyejin Kim, Sun Young Park, Sang Hyun Park, Jae-Seok Kim, Jung-Won Park, Jong-Hyeon Park and Young-Joon Ko

Vaccines 2021, 9(3), 252; https://doi.org/10.3390/vaccines9030252 - 12 Mar 2021

Cited by 5 | Viewed by 4211

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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14 pages, 832 KiB

Open AccessArticle

Targeted Modification of the Foot-And-Mouth Disease Virus Genome for Quick Cell Culture Adaptation

by Veronika Dill, Aline Zimmer, Martin Beer and Michael Eschbaumer

Vaccines 2020, 8(4), 583; https://doi.org/10.3390/vaccines8040583 - 3 Oct 2020

Cited by 5 | Viewed by 2897

Abstract

Foot-and-mouth disease virus (FMDV) causes the highly contagious foot-and-mouth disease, which is characterized by the appearance of vesicles in and around the mouth and feet of cloven-hoofed animals. BHK-21 cells are the cell line of choice for the propagation of FMDV for vaccine [...] Read more.

Foot-and-mouth disease virus (FMDV) causes the highly contagious foot-and-mouth disease, which is characterized by the appearance of vesicles in and around the mouth and feet of cloven-hoofed animals. BHK-21 cells are the cell line of choice for the propagation of FMDV for vaccine production worldwide but vary in their susceptibility for different FMDV strains. Previous studies showed that the FMDV resistance of a certain BHK cell line can be overcome by using a closely related but permissive cell line for the pre-adaptation of the virus, but the adapted strains were found to harbor several capsid mutations. In this study, these adaptive mutations were introduced into the original Asia-1 Shamir isolate individually or in combination to create a panel of 17 Asia-1 mutants by reverse genetics and examine the effects of the mutations on receptor usage, viral growth, immunogenicity and stability. A single amino acid exchange from glutamic acid to lysine at position 202 in VP1 turned out to be of major importance for productive infection of the suspension cell line BHK-2P. In consequence, two traditionally passage-derived strains and two recombinant viruses with a minimum set of mutations were tested in vivo. While the passaged-derived viruses showed a reduced particle stability, the genetically modified viruses were more stable but did not confer a protective immune response against the original virus isolate. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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11 pages, 1959 KiB

Open AccessArticle

Efficient Removal of Non-Structural Protein Using Chloroform for Foot-and-Mouth Disease Vaccine Production

by Sun Young Park, Jung-Min Lee, Ah-Young Kim, Sang Hyun Park, Sim-In Lee, Hyejin Kim, Jae-Seok Kim, Jong-Hyeon Park, Young-Joon Ko and Choi-Kyu Park

Vaccines 2020, 8(3), 483; https://doi.org/10.3390/vaccines8030483 - 27 Aug 2020

Cited by 6 | Viewed by 5310

Abstract

To differentiate foot-and-mouth disease (FMD)-infected animals from vaccinated livestock, non-structural proteins (NSPs) must be removed during the FMD vaccine manufacturing process. Currently, NSPs cannot be selectively removed from FMD virus (FMDV) culture supernatant. Therefore, polyethylene glycol (PEG) is utilized to partially separate FMDV [...] Read more.

To differentiate foot-and-mouth disease (FMD)-infected animals from vaccinated livestock, non-structural proteins (NSPs) must be removed during the FMD vaccine manufacturing process. Currently, NSPs cannot be selectively removed from FMD virus (FMDV) culture supernatant. Therefore, polyethylene glycol (PEG) is utilized to partially separate FMDV from NSPs. However, some NSPs remain in the FMD vaccine, which after repeated immunization, may elicit NSP antibodies in some livestock. To address this drawback, chloroform at a concentration of more than 2% (v/v) was found to remove NSP efficiently without damaging the FMDV particles. Contrary to the PEG-treated vaccine that showed positive NSP antibody responses after the third immunization in goats, the chloroform-treated vaccine did not induce NSP antibodies. In addition to this enhanced vaccine purity, this new method using chloroform could maximize antigen recovery and the vaccine production time could be shortened by two days due to omission of the PEG processing phase. To our knowledge, this is the first report to remove NSPs from FMDV culture supernatant by chemical addition. This novel method could revolutionize the conventional processes of FMD vaccine production. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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22 pages, 2610 KiB

Open AccessArticle

Advanced Foot-And-Mouth Disease Vaccine Platform for Stimulation of Simultaneous Cellular and Humoral Immune Responses

by Min Ja Lee, Hyundong Jo, So Hui Park, Mi-Kyeong Ko, Su-Mi Kim, Byounghan Kim and Jong-Hyeon Park

Vaccines 2020, 8(2), 254; https://doi.org/10.3390/vaccines8020254 - 28 May 2020

Cited by 19 | Viewed by 3711

Abstract

Currently available commercial foot-and-mouth disease (FMD) vaccines have various limitations, such as the slow induction and short-term maintenance of antibody titers. Therefore, a novel FMD vaccine that can rapidly induce high neutralizing antibody titers to protect the host in early stages of an [...] Read more.

Currently available commercial foot-and-mouth disease (FMD) vaccines have various limitations, such as the slow induction and short-term maintenance of antibody titers. Therefore, a novel FMD vaccine that can rapidly induce high neutralizing antibody titers to protect the host in early stages of an FMD virus infection, maintain high antibody titers for long periods after one vaccination dose, and confer full protection against clinical symptoms by simultaneously stimulating cellular and humoral immunity is needed. Here, we developed immunopotent FMD vaccine strains A-3A and A-HSP70, which elicit strong initial cellular immune response and induce humoral immune response, including long-lasting memory response. We purified the antigen (inactivated virus) derived from these immunopotent vaccine strains, and evaluated the immunogenicity and efficacy of the vaccines containing these antigens in mice and pigs. The immunopotent vaccine strains A-3A and A-HSP70 demonstrated superior immunogenicity compared with the A strain (backbone strain) in mice. The oil emulsion-free vaccine containing A-3A and A-HSP70 antigens effectively induced early, mid-term, and long-term immunity in mice and pigs by eliciting robust cellular and humoral immune responses through the activation of co-stimulatory molecules and the secretion of proinflammatory cytokines. We successfully derived an innovative FMD vaccine formulation to create more effective FMD vaccines. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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Jump to: Research

9 pages, 1192 KiB

Open AccessCase Report

Increased Ruminoreticular Temperature and Body Activity after Foot-and-Mouth Vaccination in Pregnant Hanwoo (Bos taurus coreanae) Cows

by Daehyun Kim, Jaejung Ha, Joonho Moon, Doyoon Kim, Wonhee Lee, Chanwoo Lee, Danil Kim and Junkoo Yi

Vaccines 2021, 9(11), 1227; https://doi.org/10.3390/vaccines9111227 - 22 Oct 2021

Cited by 6 | Viewed by 2636

Abstract

How does vaccination against foot-and-mouth disease (FMD) affect pregnant cows? Vaccination is the most effective method of preventing the spread of FMD, but it is linked to sporadic side effects, such as abortion and premature birth, which result in economic loss. In this [...] Read more.

How does vaccination against foot-and-mouth disease (FMD) affect pregnant cows? Vaccination is the most effective method of preventing the spread of FMD, but it is linked to sporadic side effects, such as abortion and premature birth, which result in economic loss. In this study, ruminoreticular temperature and body activity were measured before and after FMD vaccination using a ruminoreticular biocapsule sensor in Hanwoo cows at different stages of pregnancy. Compared to the unvaccinated groups, the ruminoreticular temperature increased 12 h after vaccination in the vaccinated groups. This increase in temperature is significantly correlated to vaccination. Compared to the nonpregnant and early pregnancy groups, the ruminoreticular temperature of the late pregnancy group increased sharply by more than 40 °C. Moreover, in nonpregnant and early pregnancy groups, a rapid increase in body activity was observed after FMD vaccinations. Of the 73 pregnant vaccinated cows in the study, a total of five cases had side effects (four abortions and one premature birth). Therefore, changes in the ruminoreticular temperature and activity in pregnant cows can be used as raw data to further clarify the association of FMD vaccination with the loss of a fetus and possibly predict abortion, miscarriage, and premature birth following FMD vaccination. Full article

(This article belongs to the Special Issue Foot and Mouth Disease Virus and Novel Vaccines Developments)

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