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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Veterinary Vaccines".

Deadline for manuscript submissions: 31 January 2024 | Viewed by 13671

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Special Issue Editors

Dr. Hsian-Yu Wang

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Guest Editor

International Program in Animal Vaccine Technology, International College, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
Interests: cell-culture-based vaccine manufacturing process; bioreactor; oral DNA vaccine vector; animal vaccine

Prof. Dr. David Benfield

E-Mail Website
Guest Editor

Department of Animal Sciences, The Ohio State University, Wooster Campus, 1680 Madison Avenue, Wooster, OH 44691, USA
Interests: virology, immunology and pathogenesis of diseases in large and companion animals; emerging viruses; RNA viruses; diagnostic virology

Special Issue Information

Dear Colleagues,

Scientists have attempted to use different kinds of novel technologies in animal vaccine development. Since the regulatory requirements of clinical trials for animal products are shorter than those in human vaccines, novel technologies are easier to commercialize in animal vaccine products. Many bacterial and eukaryotic cell-expressed recombinant proteins and viral vectors have been used for decades, and many kinds of immune potentiating materials, such as peptides, proteins, polymers, and emulsified oils, have been used in adjuvants. Biosafety and high immunization efficacy are the basic requirements of a vaccine. However, easily immunizing operation and low manufacturing cost are also essential for a successful animal vaccine product. This Special Issue will not only include novel antigen or adjuvant design but also cover large-scale production and manufacturing improvement technologies.

Dr. Hsian-Yu Wang
Prof. Dr. David Benfield
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

animal vaccines
novel antigen or adjuvant design
vaccines technologies

Published Papers (10 papers)

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Research

20 pages, 7455 KiB

Open AccessArticle

Development of Polycistronic Baculovirus Surface Display Vectors to Simultaneously Express Viral Proteins of Porcine Reproductive and Respiratory Syndrome and Analysis of Their Immunogenicity in Swine

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Vaccines 2023, 11(11), 1666; https://doi.org/10.3390/vaccines11111666 - 31 Oct 2023

Viewed by 650

Abstract

To simultaneously express and improve expression levels of multiple viral proteins of a porcine reproductive and respiratory syndrome virus (PRRSV), polycistronic baculovirus surface display vectors were constructed and characterized. We engineered polycistronic baculovirus surface display vectors, namely, pBacDual Display EGFP(BacDD)-2GP2-2GP4 and pBacDD-4GP5N34A/N51A (mtGP5), which simultaneously express and display the ectodomain of His-tagged GP2-gp64TM-CTD, His-tagged GP4-gp64TM-CTD, and His-tagged mtGP5-gp64TM-CTD fusion proteins of PRRSV on cell membrane of Sf-9 cells. Specific pathogen-free (SPF) pigs were administered intramuscularly in 2 doses at 21 and 35 days of age with genetic recombinant baculoviruses-infected cells. Our results revealed a high level of ELISA-specific antibodies, neutralizing antibodies, IL-4, and IFN-γ in SPF pigs immunized with the developed PRRSV subunit vaccine. To further assess the co-expression efficiency of different gene combinations, pBacDD-GP2-GP3-2GP4 and pBacDD-2mtGP5-2M constructs were designed for the co-expression of the ectodomain of His-tagged GP2-gp64TM-CTD, His-tagged GP3-gp64TM-CTD, and His-tagged GP4-gp64TM-CTD proteins as well as the ectodomain of His-tagged mtGP5-gp64TM-CTD and His-tagged M-gp64TM-CTD fusion proteins of PRRSV. To develop an ELISA assay for detecting antibodies against PRRSV proteins, the sequences encoding the ectodomain of the GP2, GP3, GP4, mtGP5, and M of PRRSV were amplified and subcloned into the pET32a vector and expressed in E. coli. In this work, the optimum conditions for expressing PRRSV proteins were evaluated, and the results suggested that 4 × 10⁵ of Sf-9 cells supplemented with 7% fetal bovine serum and infected with the recombinant baculoviruses at an MOI of 20 for three days showed a higher expression levels of the protein. Taken together, the polycistronic baculovirus surface display system is a useful tool to increase expression levels of viral proteins and to simultaneously express multiple viral proteins of PRRSV for the preparation of subunit vaccines. Full article

(This article belongs to the Special Issue Animals Vaccines)

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17 pages, 2475 KiB

Open AccessArticle

Self-Adjuvanting Calcium-Phosphate-Coated Microcrystal-Based Vaccines Induce Pyroptosis in Human and Livestock Immune Cells

Yolanda Corripio-Miyar

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Vaccines 2023, 11(7), 1229; https://doi.org/10.3390/vaccines11071229 - 11 Jul 2023

Cited by 1 | Viewed by 802

Abstract

Successful vaccines require adjuvants able to activate the innate immune system, eliciting antigen-specific immune responses and B-cell-mediated antibody production. However, unwanted secondary effects and the lack of effectiveness of traditional adjuvants has prompted investigation into novel adjuvants in recent years. Protein-coated microcrystals modified with calcium phosphate (CaP-PCMCs) in which vaccine antigens are co-immobilised within amino acid crystals represent one of these promising self-adjuvanting vaccine delivery systems. CaP-PCMCs has been shown to enhance antigen-specific IgG responses in mouse models; however, the exact mechanism of action of these microcrystals is currently unclear. Here, we set out to investigate this mechanism by studying the interaction between CaP-PCMCs and mammalian immune cells in an in vitro system. Incubation of cells with CaP-PCMCs induced rapid pyroptosis of peripheral blood mononuclear cells and monocyte-derived dendritic cells from cattle, sheep and humans, which was accompanied by the release of interleukin-1β and the activation of Caspase-1. We show that this pyroptotic event was cell–CaP-PCMCs contact dependent, and neither soluble calcium nor microcrystals without CaP (soluble PCMCs) induced pyroptosis. Our results corroborate CaP-PCMCs as a promising delivery system for vaccine antigens, showing great potential for subunit vaccines where the enhancement or find tuning of adaptive immunity is required. Full article

(This article belongs to the Special Issue Animals Vaccines)

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12 pages, 1216 KiB

Open AccessArticle

Establishment and Application of Indirect ELISAs for Detecting Antibodies against Goose Astrovirus Genotype 1 and 2

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Vaccines 2023, 11(3), 664; https://doi.org/10.3390/vaccines11030664 - 15 Mar 2023

Viewed by 1042

Abstract

Goose astrovirus (GAstV) was classified into GAstV-1 and GAstV-2, and both caused gosling viral gout. Recently, there has been no effective commercial vaccine to control the infection. It is important to establish serological methods to distinguish between the two genotypes. In this study, we reported the development and application of two indirect enzyme-linked immunosorbent assays (ELISAs) using the GAstV-1 virus and a recombinant GAstV-2 capsid protein as specific antigens to detect antibodies against GAstV-1 and GAstV-2, respectively. The optimal coating antigen concentration of indirect GAstV-1-ELISA and GAstV-2-Cap-ELISA was 1.2 µg/well and 125 ng/well, respectively. In addition, the antigen coating temperature and time, sera dilution and reaction time, and the dilution and reaction time of HRP-conjugated secondary antibody were optimized. The cut-off values were 0.315 and 0.305, and the analytical sensitivity was 1:6400 and 1:3200 for indirect GAstV-1-ELISA and GAstV-2-Cap-ELISA, respectively. The assays were able to differentiate specific sera against GAstVs, TUMV, GPV, and H9N2-AIV. The intra- and inter-plate variabilities of indirect ELISAs were less than 10%. The coincidence rate of positive sera was higher than 90%. The indirect ELISAs were further applied to test 595 goose serum samples. The results showed that the detection rates were 33.3% and 71.4% in GAstV-1-ELISA and GAstV-2-Cap-ELISA, respectively, and the co-detection rate was 31.1%, which indicates that the seroprevalence rate of GAstv-2 was higher than that of GastV-1, and the co-infection existed between GAstV-1 and GAstV-2. In summary, the developed GAstV-1-ELISA and GAstV-2-Cap-ELISA have high specificity, sensitivity, and reproducibility and can be used in the clinical detection of the antibody against GAstV-1 and GAstV-2. Full article

(This article belongs to the Special Issue Animals Vaccines)

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14 pages, 2309 KiB

Open AccessArticle

Establish a Pregnant Sow–Neonate Model to Assess Maternal Immunity of a Candidate Influenza Vaccine

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Vaccines 2023, 11(3), 646; https://doi.org/10.3390/vaccines11030646 - 14 Mar 2023

Viewed by 1126

Abstract

While it is well appreciated that maternal immunity can provide neonatal protection, the contribution of maternal vaccination toward generating such immunity is not well characterized. In our previous work, we created a candidate influenza vaccine using our chimeric hemagglutinin (HA) construct, HA-129. The HA-129 was expressed as part of a whole-virus vaccine that was built on the A/swine/Texas/4199-2/98-H3N2 backbone to generate the recombinant virus TX98-129. The TX98-129 candidate vaccine has the ability to induce broadly protective immune responses against genetically diversified influenza viruses in both mice and nursery pigs. In the current study, we established a pregnant sow–neonate model to evaluate the maternal immunity induced by this candidate vaccine to protect pregnant sows and their neonatal piglets against influenza virus infection. In pregnant sows, the results consistently show that TX98-129 induced a robust immune response against the TX98-129 virus and the parental viruses that were used to construct HA-129. After challenge with a field strain of influenza A virus, a significant increase in antibody titers was observed in vaccinated sows at both 5 and 22 days post challenge (dpc). The challenge virus was detected at a low level in the nasal swab of only one vaccinated sow at 5 dpc. Evaluation of cytokine responses in blood and lung tissue showed that levels of IFN-α and IL-1β were increased in the lung of vaccinated sows at 5 dpc, when compared to unvaccinated pigs. Further analysis of the T-cell subpopulation in PBMCs showed a higher ratio of IFN-γ-secreting CD4⁺CD8⁺ and CD8⁺ cytotoxic T cells in vaccinated sows at 22 dpc after stimulation with either challenge virus or vaccine virus. Finally, we used a neonatal challenge model to demonstrate that vaccine-induced maternal immunity can be passively transferred to newborn piglets. This was observed in the form of both increased antibody titers and deceased viral loads in neonates born from immunized sows. In summary, this study provides a swine model system to evaluate the impact of vaccination on maternal immunity and fetal/neonatal development. Full article

(This article belongs to the Special Issue Animals Vaccines)

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11 pages, 2320 KiB

Open AccessArticle

A Simple and Cost-Efficient Platform for a Novel Porcine Circovirus Type 2d (PCV2d) Vaccine Manufacturing

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Vaccines 2023, 11(1), 169; https://doi.org/10.3390/vaccines11010169 - 12 Jan 2023

Cited by 1 | Viewed by 1661

Abstract

Porcine circovirus type 2d (PCV2d) is becoming the predominant PCV genotype and considerably affects the global pig industry. Nevertheless, currently, no commercial PCV2d vaccine is available. Preventing and controlling the disease caused by PCV2d is therefore based on other genotype-based vaccines. However, their production platforms are laborious, limited in expression level, and relatively expensive for veterinary applications. To address these challenges, we have developed a simple and cost-efficient platform for a novel PCV2d vaccine production process, using fed-batch E. coli fermentation followed by cell disruption and filtration, and a single purification step via cation exchange chromatography. The process was developed at bench scale and then pilot scale, where the PCV2d subunit protein yield was approximately 0.93 g/L fermentation volume in a short production time. Moreover, we have successfully implemented this production process at two different sites, in Southeast Asia and Europe. This demonstrates transferability and the high potential for successful industrial production. Full article

(This article belongs to the Special Issue Animals Vaccines)

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14 pages, 1582 KiB

Open AccessArticle

Immunostimulating Effect of Inactivated Parapoxvirus Ovis on the Serological Response to Equine Influenza Booster Vaccination

Pierre-Olivier Vidalain

and

Stéphane Pronost

Vaccines 2022, 10(12), 2139; https://doi.org/10.3390/vaccines10122139 - 14 Dec 2022

Viewed by 1468

Abstract

Equine influenza virus (EIV) is responsible for recurring outbreaks that are detrimental to the equine industry. Vaccination is key for prevention, but the effectiveness and duration of protection provided by existing vaccines is often insufficient. In order to improve vaccine efficacy, we evaluated the benefit of immune stimulation with inactivated Parapoxvirus ovis (iPPVO) on the antibody response induced by a vaccine boost against EIV. A whole inactivated ISCOMatrix-adjuvanted equine influenza vaccine was administered alone (n = 10) or combined with iPPVO injections at D0, D2 and D4 post vaccination (n = 10) to adult horses that required a vaccine boost 6 months after the last immunization, as now recommended by the WOAH. Antibody levels were measured with the single radial haemolysis (SRH) assay at 1, 3 and 6 months post-vaccination. Results revealed that horses that received iPPVO had higher antibody levels than the control group injected with the EI vaccine alone. Although the vaccine used contains only a clade 1 and European lineage strain, the increase in protective antibodies was also observed against a clade 2 strain. Thus, immune stimulation with iPPVO, a substance already marketed as an immunostimulant, could be used to improve vaccination protocols in horses and potentially other species. Full article

(This article belongs to the Special Issue Animals Vaccines)

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13 pages, 2504 KiB

Open AccessArticle

An IgY Effectively Prevents Goslings from Virulent GAstV Infection

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Vaccines 2022, 10(12), 2090; https://doi.org/10.3390/vaccines10122090 - 07 Dec 2022

Cited by 3 | Viewed by 1060

Abstract

Goose astrovirus (GAstV) leads to viscera and joints urate deposition in 1- to 20-day-old goslings, with a mortality rate of up to 50%, posing a severe threat to entire colonies; however, there is no efficient prevention and control method for GAstV infection. This study describes a prophylactic anti-GAstV strategy based on the specific immunoglobulin Y (IgY) from egg yolk. The specific IgY was produced by 22-week-old laying hens intramuscularly immunized with the inactivated GAstV three consecutive times, with 2-week intervals. The egg yolk was collected weekly after the immunization and the anti-GAstV IgY titer was monitored using an agar gel immune diffusion assay (AGID). The results revealed that the AGID titer began to increase on day 7, reached a peak on day 49, and remained at a high level until day 77 after the first immunization. The specific IgY was prepared from the combinations of egg yolk from day 49 to day 77 through PEG-6000 precipitation. Animal experiments were conducted to evaluate the effects of prevention and treatment. The result of the minimum prophylactic dose of the IgY showed that the protection rate was 90.9% when 2.5 mg was administrated. Results of the prevention and the treatment experiments showed prevention and cure rates of over 80% when yolk antibody was administered in the early stages of the GAstV infection. These results suggested that the specific IgY obtained from immunized hens with the inactivated GAstV could be a novel strategy for preventing and treating GAstV infection. Full article

(This article belongs to the Special Issue Animals Vaccines)

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15 pages, 3911 KiB

Open AccessArticle

Nanoformulations with Leishmania braziliensis Antigens Triggered Controlled Parasite Burden in Vaccinated Golden Hamster (Mesocricetus auratus) against Visceral Leishmaniasis

Vaccines 2022, 10(11), 1848; https://doi.org/10.3390/vaccines10111848 - 31 Oct 2022

Cited by 2 | Viewed by 1407

Abstract

Leishmaniasis is a widespread vector-borne disease in Brazil, with Leishmania (Leishmania) infantum as the primary etiological agent of visceral leishmaniasis (VL). Dogs are considered the main reservoir of this parasite, whose treatment in Brazil is restricted to the use of veterinary medicines, which do not promote a parasitological cure. Therefore, efficient vaccine development is the best approach to Canine Visceral Leishmaniasis (CVL) control. With this in mind, this study used hamsters (Mesocricetus auratus) as an experimental model in an anti-Leishmania preclinical vaccine trial to evaluate the safety, antigenicity, humoral response, and effects on tissue parasite load. Two novel formulations of nanoparticles made from poly(D, L-lactic) acid (PLA) polymer loading Leishmania braziliensis crude antigen (LB) exhibiting two different particle sizes were utilized: LBPSmG (570 nm) and LBPSmP (388 nm). The results showed that the nanoparticles were safe and harmless to hamsters and were antigenic with the induction in LBSap, LBPSmG, and LBPSmG groups of total anti-Leishmania IgG antibodies 30 days after challenge, which persists 200 days in LBSap and LBPSmP. At the same time, a less pronounced hepatosplenomegaly in LBSap, LBPSmG, and LBPSmP was found when compared to control groups, as well as a less pronounced inflammatory infiltrate and granuloma formation in the spleen. Furthermore, significant reductions of 84%, 81%, and 90% were observed in spleen parasite burden accessed by qPCR in the LBSap, LBPSmG, and LBPSmP groups, respectively. In this way, LBSap, LBPSmG, and LBPSmP formulations showed better results in vaccinated and L. infantum-challenged animals in further reducing parasitic load in the spleen and attenuating lesions in liver and splenic tissues. This results in safe, harmless nanoformulation vaccines with significant immunogenic and infection control potential. In addition, animals vaccinated with LBPSmP had an overall reduction in parasite burden in the spleen, indicating that a smaller nanoparticle could be more efficient in targeting antigen-presenting cells. Full article

(This article belongs to the Special Issue Animals Vaccines)

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11 pages, 2563 KiB

Open AccessArticle

Lumpy Skin Disease Virus with Four Knocked Out Genes Was Attenuated In Vivo and Protects Cattle from Infection

Olga Chervyakova

Aisha Issabek

Kulyaisan Sultankulova

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Vaccines 2022, 10(10), 1705; https://doi.org/10.3390/vaccines10101705 - 12 Oct 2022

Cited by 1 | Viewed by 1899

Abstract

Vaccination with live attenuated vaccines is a key element in the prevention of lumpy skin disease. The mechanism of virus attenuation by long-term passaging in sensitive systems remains unclear. Targeted inactivation of virulence genes is the most promising way to obtain attenuated viruses. Four virulence genes in the genome of the lumpy skin disease virus (LSDV) Dermatitis nodulares/2016/Atyrau/KZ were sequentially knocked out by homologous recombination under conditions of temporary dominant selection. The recombinant LSDV Atyrau-5BJN(IL18) with a knockout of the LSDV005, LSDV008, LSDV066 and LSDV142 genes remained genetically stable for ten passages and efficiently replicated in cells of lamb testicles, saiga kidney and bovine kidney. In vivo experiments with cattle have shown that injection of the LSDV Atyrau-5BJN(IL18) at a high dose does not cause disease in animals or other deviations from the physiological norm. Immunization of cattle with the LSDV Atyrau-5BJN(IL18) induced the production of virus-neutralizing antibodies in titers of 4–5 log2. The challenge did not cause disease in immunized animals. The knockout of four virulence genes resulted in attenuation of the virulent LSDV without loss of immunogenicity. The recombinant LSDV Atyrau-5BJN(IL18) is safe for clinical use, immunogenic and protects animals from infection with the virulent LSDV. Full article

(This article belongs to the Special Issue Animals Vaccines)

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13 pages, 1780 KiB

Open AccessArticle

Evaluation of the Immune Response Afforded by Combined Immunization with Orf Virus DNA and Subunit Vaccine in Mice

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Vaccines 2022, 10(9), 1499; https://doi.org/10.3390/vaccines10091499 - 08 Sep 2022

Cited by 3 | Viewed by 1511

Abstract

Contagious ecthyma (Orf) is a highly contagious disease caused by Orf virus (ORFV) infection. Orf is prevalent all over the world and, not only affects the healthy development of sheep husbandry, but also threatens human health. However, there are no safe and effective vaccines or drugs for the prevention and treatment of Orf at present. In this study, we constructed a DNA plasmid expressing ORFV B2L and F1L genes as a DNA vaccine candidate, with purified B2L full-length protein and F1L truncated protein as subunit vaccine candidates. BALB/c mice were immunized with the DNA vaccine, subunit vaccine, as well as DNA prime-protein boost strategies. The results showed that compared with the DNA vaccine and subunit vaccine alone, the DNA prime-protein boost immunization group had a higher level of specific antibodies, stronger lymphocyte proliferation, and higher expression of cytokines such as IL-2, IL-4, IL-6, IFN-γ, and TNF-α, which are considered to cause a Th1/Th2 mixed cytokine response. Our results demonstrated that the DNA prime-protein boost immunization strategy induced stronger humoral and cellular immune responses, which have potential advantages in preventing ORFV infection. Full article

(This article belongs to the Special Issue Animals Vaccines)

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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: A Simple and Cost-Efficient Platform for a Novel Porcine Circovirus Type 2d (PCV2d) Vaccine Manufacturing
Author:
Highlights: • We demonstrate, for the first time, a simple and cost-efficient manufacturing process of PCV2d vaccines • A 20-L fed-batch fermentation and one-step purification yield 1g/L which is sufficient to vaccinate as many as 200,000 pigs with one dose • The platform has been evaluated by technology transfer to UK site and shown to achieve high yields of PCV2d vaccine

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