Research

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19 pages, 3532 KiB

Open AccessArticle

Bestatin, A Pluripotent Immunomodulatory Small Molecule, Drives Robust and Long-Lasting Immune Responses as an Adjuvant in Viral Vaccines

by Hyeong Won Kim, Mi-Kyeong Ko, So Hui Park, Seokwon Shin, Su-Mi Kim, Jong-Hyeon Park and Min Ja Lee

Vaccines 2023, 11(11), 1690; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines11111690 - 04 Nov 2023

Cited by 1 | Viewed by 1123

Abstract

An inactivated whole-virus vaccine is currently used to prevent foot-and-mouth disease (FMD). Although this vaccine is effective, it offers short-term immunity that requires regular booster immunizations and has several side effects, including local reactions at the vaccination site. To address these limitations, herein, [...] Read more.

An inactivated whole-virus vaccine is currently used to prevent foot-and-mouth disease (FMD). Although this vaccine is effective, it offers short-term immunity that requires regular booster immunizations and has several side effects, including local reactions at the vaccination site. To address these limitations, herein, we evaluated the efficacy of bestatin as a novel small molecule adjuvant for inactivated FMD vaccines. Our findings showed that the FMD vaccine formulated with bestatin enhanced early, intermediate-, and particularly long-term immunity in experimental animals (mice) and target animals (pigs). Furthermore, cytokines (interferon (IFN)α, IFNβ, IFNγ, and interleukin (IL)-29), retinoic acid-inducible gene (RIG)-I, and T-cell and B-cell core receptors (cluster of differentiation (CD)28, CD19, CD21, and CD81) markedly increased in the group that received the FMD vaccine adjuvanted with bestatin in pigs compared with the control. These results indicate the significant potential of bestatin to improve the efficacy of inactivated FMD vaccines in terms of immunomodulatory function for the simultaneous induction of potent cellular and humoral immune response and a long-lasting memory response. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Adjuvants against Viral Diseases)

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15 pages, 3275 KiB

Open AccessArticle

Recombinant Porcine Interferon-α Decreases Pseudorabies Virus Infection

by Bowen Song, Wenkang Wei, Xueyi Liu, Yaoyao Huang, Shuaiqi Zhu, Lin Yi, Eerdunfu, Hongxing Ding, Mingqiu Zhao and Jinding Chen

Vaccines 2023, 11(10), 1587; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines11101587 - 12 Oct 2023

Viewed by 1187

Abstract

Interferon (IFN) is a cell-secreted cytokine possessing biological activities including antiviral functioning, immune regulation, and others. Interferon-alpha (IFN-α) mainly derives from plasmacytoid dendritic cells, which activate natural killer cells and regulate immune responses. IFN-α responds to the primary antiviral mechanism in the innate [...] Read more.

Interferon (IFN) is a cell-secreted cytokine possessing biological activities including antiviral functioning, immune regulation, and others. Interferon-alpha (IFN-α) mainly derives from plasmacytoid dendritic cells, which activate natural killer cells and regulate immune responses. IFN-α responds to the primary antiviral mechanism in the innate immune system, which can effectively cure acute infectious diseases. Pseudorabies (PR) is an acute infectious disease caused by pseudorabies virus (PRV). The clinical symptoms of PRV are as follows: reproductive dysfunction among pregnant sows and high mortality rates among piglets. These pose a severe threat to the swine industry. Related studies show that IFN-α has broad applications in preventing and treating viral diseases. Therefore, a PRV mouse model using artificial infection was established in this study to explore the pathogenic effect of IFN-α on PRV. We designed a sequence with IFN-α4 (M28623, Genbank) and cloned it on the lentiviral vector. CHO-K1 cells were infected and identified using WB and RT-PCR; a CHO-K1 cell line with a stable expression of the recombinant protein PoIFN-α was successfully constructed. H&E staining and virus titer detection were used to investigate the recombinant protein PoIFN-α’s effect on PR in BALB/c mice. The results show that the PoIFN-α has a preventive and therapeutic impact on PR. In conclusion, the recombinant protein can alleviate symptoms and reduce the replication of PRV in vivo. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Adjuvants against Viral Diseases)

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14 pages, 483 KiB

Open AccessArticle

Safety of the Administration of an Inactivated PCV2a/PCV2b/Mycoplasma Hyopneumoniae Vaccine to Pregnant and Lactating Sows and Gilts

by Elena Pérez, Cristina Venegas-Vargas, Andrea Heinz, Megan Smutzer, Lucas P. Taylor, Yvette Diamondidis, Nevena Mangarova, Tara Hansen, José Angulo, Meggan Bandrick and Monica Balasch

Vaccines 2023, 11(9), 1483; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines11091483 - 14 Sep 2023

Viewed by 1134

Abstract

Porcine Circovirus type 2 (PCV2) vaccination of gilts during acclimation has become a routine practice in commercial pig farms to homogenize herd immunity to PCV2 and reduce the impact of diseases associated with PCV2 infection, namely reproductive, respiratory, systemic, and other PCV2-associated diseases. [...] Read more.

Porcine Circovirus type 2 (PCV2) vaccination of gilts during acclimation has become a routine practice in commercial pig farms to homogenize herd immunity to PCV2 and reduce the impact of diseases associated with PCV2 infection, namely reproductive, respiratory, systemic, and other PCV2-associated diseases. The periodic mass vaccination of sows, with the same objectives, is also common. To ensure mass vaccination is an appropriate health management tool, demonstrating that the vaccine is safe in different sow/gilt physiological stages is necessary. The objective of the present studies was to evaluate safety of a PCV2a/PCV2b/Mycoplasma hyopneumoniae (PCV2a2bMHP) killed vaccine in sows and gilts during gestation and lactation, under controlled experimental pen conditions, and during gestation, mimicking mass vaccination, under field conditions. Safety was assessed by monitoring for immediate adverse reactions after vaccination, rectal temperatures after vaccination (controlled experimental pen studies only), local and systemic reactions, and reproductive performance (studies conducted during pregnancy) or lactation performance (studies conducted during lactation). In total, 416 sows/gilts were enrolled, and more than 4000 piglets were observed during their first week of life, under field conditions. In both controlled experimental and field studies, no immediate anaphylactic type reactions were observed after vaccination and the incidence of adverse events, such as depression or decreased appetite, was acceptable for what is expected in a swine herd. In the studies conducted during gestation, vaccination did not significantly increase rectal temperature of the vaccinated animals. Sow reproductive outcomes were not affected by vaccination. The farrowing rate of animals participating in the field study was higher than the historic averages of the farms. In the laboratory studies conducted during the first and second half of gestation, no differences in reproductive outcome were observed between vaccinated and non-vaccinated animals. However, sows vaccinated during lactation experienced a transient hyperthermia which did not affect milk production since the piglets’ average daily weight gain was not affected. The previously described results confirm that the administration of a PCV2a2bMHP vaccine was safe in the tested conditions. All the anticipated benefits of sow and gilt PCV2 vaccination, such as homogenization of PCV2 antibody titers or reduction in PCV2 circulation in the herd, would not be masked by potential adverse events due to herd vaccination. In conclusion, the administration of a PCV2a2bMHP vaccine to sows and gilts during different stages of gestation and during lactation is safe. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Adjuvants against Viral Diseases)

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13 pages, 1413 KiB

Open AccessArticle

A Plant-Derived Maternal Vaccine against Porcine Epidemic Diarrhea Protects Piglets through Maternally Derived Immunity

by Eun-Ju Sohn, Hyangju Kang, Kyungmin Min, Minhee Park, Ju-Hun Kim, Hwi-Won Seo, Sang-Joon Lee, Heeyeon Kim, Dongseob Tark, Ho-Seong Cho, Bo-Hwa Choi and Yeonsu Oh

Vaccines 2023, 11(5), 965; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines11050965 - 09 May 2023

Cited by 2 | Viewed by 1762

Abstract

Newborn piglets are susceptible to a highly contagious enteritis caused by the porcine epidemic diarrhea virus (PEDV), associated with high levels of mortality worldwide. There is pressing need for a rapid, safe, and cost-effective vaccine to safeguard pigs from getting infected by PEDV. [...] Read more.

Newborn piglets are susceptible to a highly contagious enteritis caused by the porcine epidemic diarrhea virus (PEDV), associated with high levels of mortality worldwide. There is pressing need for a rapid, safe, and cost-effective vaccine to safeguard pigs from getting infected by PEDV. PEDV belongs to the coronavirus family and is characterized by high levels of mutability. The primary goal of a PEDV vaccine is to provide immunity to newborn piglets through vaccination of sows. Plant-based vaccines are becoming more popular because they have low manufacturing costs, are easily scalable, have high thermostability, and a long shelf life. This is in contrast to conventional vaccines which include inactivated, live, and/or recombinant types that can be expensive and have limited ability to respond to rapidly mutating viruses. The binding of the virus to host cell receptors is primarily facilitated by the N-terminal subunit of the viral spike protein (S1), which also contains several epitopes that are recognized by virus-neutralizing antibodies. As a result, we generated a recombinant S1 protein using a plant-based vaccine platform. We found that the recombinant protein was highly glycosylated, comparable to the native viral antigen. Vaccination of pregnant sows at four and two weeks before farrowing led to the development of humoral immunity specific to S1 in the suckling piglets. In addition, we noted significant viral neutralization titers in both vaccinated sows and piglets. When challenged with PEDV, piglets born from vaccinated sows displayed less severe clinical symptoms and significantly lower mortality rates compared to piglets born from non-vaccinated sows. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Adjuvants against Viral Diseases)

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22 pages, 4126 KiB

Open AccessArticle

Efficacy of a Novel Multiepitope Vaccine Candidate against Foot-and-Mouth Disease Virus Serotype O and A

by W. A. Gayan Chathuranga, Chamith Hewawaduge, N. A. Nadeeka Nethmini, Tae-Hwan Kim, Ju Hun Kim, Young-Hoon Ahn, In-Joong Yoon, Sung-Sik Yoo, Jong-Hyeon Park and Jong-Soo Lee

Vaccines 2022, 10(12), 2181; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10122181 - 19 Dec 2022

Cited by 8 | Viewed by 2022

Abstract

Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease in cloven-hoofed animals. To prevent the spread of FMD virus (FMDV), traditional inactivated vaccines are used to immunize susceptible animals in disease-endemic countries. However, the inactivated FMD vaccine has several limitations, including [...] Read more.

Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease in cloven-hoofed animals. To prevent the spread of FMD virus (FMDV), traditional inactivated vaccines are used to immunize susceptible animals in disease-endemic countries. However, the inactivated FMD vaccine has several limitations, including safety concerns. To overcome these limitations, subunit proteins have been studied as alternative vaccine candidates. In this study, we designed two multiepitope recombinant proteins (OVM and AVM) containing antigenic sites (residue of VP1 132–162 and residue of VP1 192–212) of three topotypes of FMDV serotype O or three topotypes of FMDV serotype A. Each recombinant protein was efficiently expressed in Escherichia coli with high solubility, and the immunogenicity and protective efficacy of the proteins as FMD vaccine candidates were evaluated. The results showed that OVM and AVM emulsified with ISA201 adjuvant induced effective antigen-specific humoral and cell-mediated immune responses and successfully protected mice from O/Jincheon/SKR/2014, O/VET/2013, and A/Malaysia/97 viruses. In addition, intramuscular immunization of pigs with the OVM and AVM emulsified with ISA201 elicited effective levels of neutralizing antibodies to the viruses with homologous epitopes. Importantly, OVM-AVM emulsified with CAvant^®SOE-X adjuvant conferred 100% protection against the O/Jincheon/SKR/2014 virus with homologous residues and 75% protection against A/SKR/GP/2018 with heterologous residues. The results presented in this study suggest that the combination of OVM and AVM protein with an effective adjuvant could yield an effective and safe vaccine candidate for the prevention and control of foot-and-mouth disease. In addition, our results provide a vaccine platform that can safely, cost-efficiently, and rapidly generate protective vaccine candidates against diverse FMDVs. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Adjuvants against Viral Diseases)

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9 pages, 8048 KiB

Open AccessArticle

A Sandwich ELISA for Quality Control of PCV2 Virus-like Particles Vaccine

by Mingxia Sun, Shanghui Wang, Zheng Fang, Man Zhao, Yanfei Gao, Tongqing An, Yabin Tu, Haiwei Wang and Xuehui Cai

Vaccines 2022, 10(12), 2175; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10122175 - 18 Dec 2022

Viewed by 1678

Abstract

Porcine circovirus type 2 (PCV2) is a highly prevalent virus in pig farms worldwide that causes significant economic losses in the swine industry. The PCV2 virus-like particles (VLPs) are potent subunit vaccines that are widely used. Currently, the adopted quality control of VLPs [...] Read more.

Porcine circovirus type 2 (PCV2) is a highly prevalent virus in pig farms worldwide that causes significant economic losses in the swine industry. The PCV2 virus-like particles (VLPs) are potent subunit vaccines that are widely used. Currently, the adopted quality control of VLPs vaccines is mainly based in animal testing, the titration of neutralizing antibodies, or other biochemical/biophysical assays. In this study, we generated a monoclonal antibody that can distinguish assembled PCV2 VLPs from the capsid proteins. Subsequently, a convenient Sandwich ELISA was developed based on the monoclonal antibody (mAb) that recognizes the PCV2 VLPs specifically. This assay can be used for the quantity and quality control of PCV2 VLPs vaccines for both the intermediate or final products with high accuracy. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Adjuvants against Viral Diseases)

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13 pages, 2706 KiB

Open AccessArticle

The Deletion of US3 Gene of Pseudorabies Virus (PRV) ΔgE/TK Strain Induces Increased Immunogenicity in Mice

by Meng-Meng Deng, Ya-Wei Sun, Chen-Meng Ding, Xi-Ya Xu, Zi-Yi Guo, Zi-Wei Han, Chen-Zhe Lv, Jiang-Kun Qi, Yong-Tao Li, Xia Yang, Lin-Yang Yu and Lu Chen

Vaccines 2022, 10(10), 1603; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10101603 - 23 Sep 2022

Cited by 1 | Viewed by 1723

Abstract

Re-emerging pseudorabies (PR) caused by pseudorabies virus (PRV) variant has been prevailing among immunized herds in China since 2011, indicating that commercially available PR vaccine strains couldn’t provide complete protection against novel, epidemic PRV variant. Before this study, a gE/TK-gene-deleted virus (PRV ΔgE/TK) [...] Read more.

Re-emerging pseudorabies (PR) caused by pseudorabies virus (PRV) variant has been prevailing among immunized herds in China since 2011, indicating that commercially available PR vaccine strains couldn’t provide complete protection against novel, epidemic PRV variant. Before this study, a gE/TK-gene-deleted virus (PRV ΔgE/TK) was constructed from PRV QYY2012 variant through homologous recombination and Cre/LoxP system. Here, PRV ΔgE/TK/US3 strain was generated by deleting US3 gene based on PRV ΔgE/TK strain using the same method. The growth characteristics of PRV ΔgE/TK/US3 were analogous to that of PRV ΔgE/TK. Moreover, the deletion of US3 gene could promote apoptosis, upregulate the level of swine leukocyte antigen class I molecule (SLA-I) in vitro, and relieve inflammatory response in inoculated BALB/c mice. Subsequently, the safety and immunogenicity of PRV ΔgE/TK/US3 was evaluated as a vaccine candidate in mice. The results revealed that PRV ΔgE/TK/US3 was safe for mice, and mice vaccinated with PRV ΔgE/TK/US3 could induce a higher level of PRV-specific neutralizing antibodies and cytokines, including IFN-γ, IL-2 and IL-4, also higher level of CD8⁺ CD69⁺ Tissue-Resident Memory T cells (TRM). The results show that the deletion of US3 gene of PRV ΔgE/TK strain could induce increased immunogenicity, indicating that the PRV ΔgE/TK/US3 strain is a promising vaccine candidate for preventing and controlling of the epidemic PR in China. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Adjuvants against Viral Diseases)

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16 pages, 3642 KiB

Open AccessArticle

Age-Dependent Dynamics of Maternally Derived Antibodies (MDAs) and Understanding MDA-Mediated Immune Tolerance in Foot-and-Mouth Disease-Vaccinated Pigs

by Sehee Shin, So Hui Park, Jong-Hyeon Park, Su-Mi Kim and Min Ja Lee

Vaccines 2022, 10(5), 677; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10050677 - 24 Apr 2022

Cited by 5 | Viewed by 2155

Abstract

Vaccine-induced active immunity in young animals may be compromised via interference caused by maternally derived antibodies (MDAs). Since the level, titer, and half-life of MDAs vary per individual, it is difficult to determine the appropriate timing of foot-and-mouth disease (FMD) vaccination in the [...] Read more.

Vaccine-induced active immunity in young animals may be compromised via interference caused by maternally derived antibodies (MDAs). Since the level, titer, and half-life of MDAs vary per individual, it is difficult to determine the appropriate timing of foot-and-mouth disease (FMD) vaccination in the field. In order to better understand the age-dependent characteristics of MDA in sows and piglets as well as the phenomenon of reduced vaccine-mediated active immunity due to MDAs, this study sought to determine antibody titers through structural protein (SP) O, A ELISA analyses, and virus-neutralizing (VN) antibody titers as well as their half-lives in the sera of sows and piglets derived from FMD-vaccinated mother. Furthermore, immunoglobulin (Ig) subtypes, such as IgG, IgM, and IgA, in serum were also evaluated. To understand the correlation between the inhibition of vaccine-mediated active immunity by MDA-mediated passive immunity and regulatory T (T_reg) cells, T_reg-related cytokine levels were explored. Our findings will help to predict the optimal timing of vaccination for overcoming MDAs and inducing a robust vaccine-mediated immune response in young individuals vaccinated against FMD. They also add to our understanding of MDA characteristics and interference, providing insight for the development of innovative strategies and novel FMD vaccine for overcoming such interference. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Adjuvants against Viral Diseases)

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Review

Jump to: Research

17 pages, 1262 KiB

Open AccessReview

Development of Foot-and-Mouth Disease Vaccines in Recent Years

by Zhimin Lu, Shu Yu, Weijun Wang, Wenxian Chen, Xinyan Wang, Keke Wu, Xiaowen Li, Shuangqi Fan, Hongxing Ding, Lin Yi and Jingding Chen

Vaccines 2022, 10(11), 1817; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10111817 - 28 Oct 2022

Cited by 5 | Viewed by 3059

Abstract

Foot-and-mouth disease (FMD) is a serious disease affecting the global graziery industry. Once an epidemic occurs, it can lead to economic and trade stagnation. In recent decades, FMD has been effectively controlled and even successfully eradicated in some countries or regions through mandatory [...] Read more.

Foot-and-mouth disease (FMD) is a serious disease affecting the global graziery industry. Once an epidemic occurs, it can lead to economic and trade stagnation. In recent decades, FMD has been effectively controlled and even successfully eradicated in some countries or regions through mandatory vaccination with inactivated foot-and-mouth disease vaccines. Nevertheless, FMD still occurs in some parts of Africa and Asia. The transmission efficiency of foot-and-mouth disease is high. Both disease countries and disease-free countries should always be prepared to deal with outbreaks of FMD. The development of vaccines has played a key role in this regard. This paper summarizes the development of several promising vaccines including progress and design ideas. It also provides ways to develop a new generation of vaccines for FMDV and other major diseases. Full article

(This article belongs to the Special Issue Veterinary Vaccines and Adjuvants against Viral Diseases)

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