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18 pages, 3204 KiB

Open AccessArticle

Assessment of an LSDV-Vectored Vaccine for Heterologous Prime-Boost Immunizations against HIV

by Ros Chapman, Michiel van Diepen, Nicola Douglass, Shireen Galant, Mohamed Jaffer, Emmanuel Margolin, Phindile Ximba, Tandile Hermanus, Penny L. Moore and Anna-Lise Williamson

Vaccines 2021, 9(11), 1281; https://doi.org/10.3390/vaccines9111281 - 5 Nov 2021

Cited by 5 | Viewed by 2709

Abstract

The modest protective effects of the RV144 HIV-1 vaccine trial have prompted the further exploration of improved poxvirus vector systems that can yield better immune responses and protection. In this study, a recombinant lumpy skin disease virus (LSDV) expressing HIV-1 CAP256.SU gp150 (Env) [...] Read more.

The modest protective effects of the RV144 HIV-1 vaccine trial have prompted the further exploration of improved poxvirus vector systems that can yield better immune responses and protection. In this study, a recombinant lumpy skin disease virus (LSDV) expressing HIV-1 CAP256.SU gp150 (Env) and a subtype C mosaic Gag was constructed (LSDVGC5) and compared to the equivalent recombinant modified vaccinia Ankara (MVAGC5). In vitro characterization confirmed that cells infected with recombinant LSDV produced Gag virus-like particles containing Env, and that Env expressed on the surface of the cells infected with LSDV was in a native-like conformation. This candidate HIV-1 vaccine (L) was tested in a rabbit model using different heterologous vaccination regimens, in combination with DNA (D) and MVA (M) vectors expressing the equivalent HIV-1 antigens. The four different vaccination regimens (DDMMLL, DDMLML, DDLMLM, and DDLLMM) all elicited high titers of binding and Tier 1A neutralizing antibodies (NAbs), and some regimens induced Tier 1B NAbs. Furthermore, two rabbits in the DDLMLM group developed low levels of autologous Tier 2 NAbs. The humoral immune responses elicited against HIV-1 Env by the recombinant LSDVGC5 were comparable to those induced by MVAGC5. Full article

(This article belongs to the Special Issue Lumpy Skin Disease Control and Vaccines)

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25 pages, 5207 KiB

Open AccessArticle

The Development of Dual Vaccines against Lumpy Skin Disease (LSD) and Bovine Ephemeral Fever (BEF)

by Nicola Douglass, Ruzaiq Omar, Henry Munyanduki, Akiko Suzuki, Warren de Moor, Paidamwoyo Mutowembwa, Alri Pretorius, Tshifhiwa Nefefe, Antoinette van Schalkwyk, Pravesh Kara, Livio Heath and Anna-Lise Williamson

Vaccines 2021, 9(11), 1215; https://doi.org/10.3390/vaccines9111215 - 20 Oct 2021

Cited by 9 | Viewed by 4909

Abstract

Dual vaccines (n = 6) against both lumpy skin disease (LSD) and bovine ephemeral fever (BEF) were constructed, based on the BEFV glycoprotein (G) gene, with or without the BEFV matrix (M) protein gene, inserted into one of two different LSDV backbones, [...] Read more.

Dual vaccines (n = 6) against both lumpy skin disease (LSD) and bovine ephemeral fever (BEF) were constructed, based on the BEFV glycoprotein (G) gene, with or without the BEFV matrix (M) protein gene, inserted into one of two different LSDV backbones, nLSDV∆SOD-UCT or nLSDVSODis-UCT. The inserted gene cassettes were confirmed by PCR; and BEFV protein was shown to be expressed by immunofluorescence. The candidate dual vaccines were initially tested in a rabbit model; neutralization assays using the South African BEFV vaccine (B-Phemeral) strain showed an African consensus G protein gene (Gb) to give superior neutralization compared to the Australian (Ga) gene. The two LSDV backbones expressing both Gb and M BEFV genes were tested in cattle and shown to elicit neutralizing responses to LSDV as well as BEFV after two inoculations 4 weeks apart. The vaccines were safe in cattle and all vaccinated animals were protected against virulent LSDV challenge, unlike a group of control naïve animals, which developed clinical LSD. Both neutralizing and T cell responses to LSDV were stimulated upon challenge. After two inoculations, all vaccinated animals produced BEFV neutralizing antibodies ≥ 1/20, which is considered protective for BEF. Full article

(This article belongs to the Special Issue Lumpy Skin Disease Control and Vaccines)

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13 pages, 4698 KiB

Open AccessArticle

Advancements in the Growth and Construction of Recombinant Lumpy Skin Disease Virus (LSDV) for Use as a Vaccine Vector

by Michiel van Diepen, Rosamund Chapman, Nicola Douglass, Leah Whittle, Nicole Chineka, Shireen Galant, Christian Cotchobos, Akiko Suzuki and Anna-Lise Williamson

Vaccines 2021, 9(10), 1131; https://doi.org/10.3390/vaccines9101131 - 4 Oct 2021

Cited by 9 | Viewed by 3511

Abstract

Attenuated vaccine strains of lumpy skin disease virus (LSDV) have become increasingly popular as recombinant vaccine vectors, to target both LSDV, as well as other pathogens, including human infectious agents. Historically, these vaccine strains and recombinants were generated in primary (lamb) testis (LT) [...] Read more.

Attenuated vaccine strains of lumpy skin disease virus (LSDV) have become increasingly popular as recombinant vaccine vectors, to target both LSDV, as well as other pathogens, including human infectious agents. Historically, these vaccine strains and recombinants were generated in primary (lamb) testis (LT) cells, Madin–Darby bovine kidney (MDBK) cells or in eggs. Growth in eggs is a laborious process, the use of primary cells has the potential to introduce pathogens and MDBK cells are known to harbor bovine viral diarrhea virus (BVDV). In this study, data is presented to show the growth of an attenuated LSDV strain in baby hamster kidney (BHK-21) cells. Subsequently, a recombinant LSDV vaccine was generated in BHK-21 cells. Partial growth was also observed in rabbit kidney cells (RK13), but only when the vaccinia virus host range gene K1L was expressed. Despite the limited growth, the expression of K1L was enough to serve as a positive selection marker for the generation of recombinant LSDV vaccines in RK13 cells. The simplification of generating (recombinant) LSDV vaccines shown here should increase the interest for this platform for future livestock vaccine development and, with BHK-21 cells approved for current good manufacturing practice, this can be expanded to human vaccines as well. Full article

(This article belongs to the Special Issue Lumpy Skin Disease Control and Vaccines)

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16 pages, 1031 KiB

Open AccessArticle

The Importance of Quality Control of LSDV Live Attenuated Vaccines for Its Safe Application in the Field

by Andy Haegeman, Ilse De Leeuw, Meruyert Saduakassova, Willem Van Campe, Laetitia Aerts, Wannes Philips, Akhmetzhan Sultanov, Laurent Mostin and Kris De Clercq

Vaccines 2021, 9(9), 1019; https://doi.org/10.3390/vaccines9091019 - 13 Sep 2021

Cited by 22 | Viewed by 3921

Abstract

Vaccination is an effective approach to prevent, control and eradicate diseases, including lumpy skin disease (LSD). One of the measures to address farmer hesitation to vaccinate is guaranteeing the quality of vaccine batches. The purpose of this study was to demonstrate the importance [...] Read more.

Vaccination is an effective approach to prevent, control and eradicate diseases, including lumpy skin disease (LSD). One of the measures to address farmer hesitation to vaccinate is guaranteeing the quality of vaccine batches. The purpose of this study was to demonstrate the importance of a quality procedure via the evaluation of the LSD vaccine, Lumpivax (Kevevapi). The initial PCR screening revealed the presence of wild type LSD virus (LSDV) and goatpox virus (GTPV), in addition to vaccine LSDV. New phylogenetic PCRs were developed to characterize in detail the genomic content and a vaccination/challenge trial was conducted to evaluate the impact on efficacy and diagnostics. The characterization confirmed the presence of LSDV wild-, vaccine- and GTPV-like sequences in the vaccine vial and also in samples taken from the vaccinated animals. The analysis was also suggestive for the presence of GTPV-LSDV (vaccine/wild) recombinants. In addition, the LSDV status of some of the animal samples was greatly influenced by the differentiating real-PCR used and could result in misinterpretation. Although the vaccine was clinically protective, the viral genomic content of the vaccine (being it multiple Capripox viruses and/or recombinants) and the impact on the diagnostics casts serious doubts of its use in the field. Full article

(This article belongs to the Special Issue Lumpy Skin Disease Control and Vaccines)

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15 pages, 10134 KiB

Open AccessArticle

Investigation of Post Vaccination Reactions of Two Live Attenuated Vaccines against Lumpy Skin Disease of Cattle

by Zahra Bamouh, Jihane Hamdi, Siham Fellahi, Slimane Khayi, Mohammed Jazouli, Khalid Omari Tadlaoui, Ouafaa Fassi Fihri, Eeva Tuppurainen and Mehdi Elharrak

Vaccines 2021, 9(6), 621; https://doi.org/10.3390/vaccines9060621 - 8 Jun 2021

Cited by 21 | Viewed by 4537

Abstract

Lumpy skin disease virus (LSDV) causes an economically important disease in cattle. The only method for successful control is early diagnosis and efficient vaccination. Adverse effects of vaccination such as local inflammation at the injection site and localized or generalized skin lesions in [...] Read more.

Lumpy skin disease virus (LSDV) causes an economically important disease in cattle. The only method for successful control is early diagnosis and efficient vaccination. Adverse effects of vaccination such as local inflammation at the injection site and localized or generalized skin lesions in some vaccinated animals have been reported with live vaccines. The aim of this work was to compare the safety of two lumpy skin disease (LSD) vaccine strains, Kenyan (Kn) Sheep and Goat Pox (KSGP O-240) and LSDV Neethling (Nt) strain, and to determine the etiology of the post-vaccination (pv) reactions observed in cattle. Experimental cattle were vaccinated under controlled conditions with Nt- and KSGP O-240-based vaccines, using two different doses, and animals were observed for 3 months for any adverse reactions. Three out of 45 cattle vaccinated with LSDV Nt strain (6.7%) and three out of 24 cattle vaccinated with Kn strain (12.5%) presented LSD-like skin nodules, providing evidence that the post-vaccination lesions may not be strain-dependent. Lesions appeared 1–3 weeks after vaccination and were localized in the neck or covering the whole body. Animals recovered after 3 weeks. There is a positive correlation between the vaccine dose and the appearance of skin lesions in vaccinated animals; at the 105 dose, 12% of the animals reacted versus 3.7% at the 104 dose. Both strains induced solid immunity when protection was measured by neutralizing antibody seroconversion. Full article

(This article belongs to the Special Issue Lumpy Skin Disease Control and Vaccines)

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11 pages, 2911 KiB

Open AccessArticle

Differentiation of Capripox Viruses by Nanopore Sequencing

by Kamal H. Eltom, Anna Christina Althoff, Sören Hansen, Susanne Böhlken-Fascher, Ausama Yousif, Hussein A. El-Sheikh, Ahmed A. ElWakeel, Mahmoud A. Elgamal, Hadeer M. Mossa, Emad A. Aboul-Soud, Janika Wolff, Christian Korthase, Bernd Hoffmann, Nabawia M. Adam, Sanaa A. Abdelaziz, Mohamed A. Shalaby and Ahmed Abd El Wahed

Vaccines 2021, 9(4), 351; https://doi.org/10.3390/vaccines9040351 - 6 Apr 2021

Cited by 5 | Viewed by 3853

Abstract

The genus capripoxvirus (CaPV), family Poxviridae, includes three virus species: goatpox virus (GPV), sheeppox virus (SPV) and lumpy skin disease virus (LSDV). CaPV causes disease outbreaks with consequent economic losses in Africa and the Middle East. LSDV has recently spread to Southeast [...] Read more.

The genus capripoxvirus (CaPV), family Poxviridae, includes three virus species: goatpox virus (GPV), sheeppox virus (SPV) and lumpy skin disease virus (LSDV). CaPV causes disease outbreaks with consequent economic losses in Africa and the Middle East. LSDV has recently spread to Southeast Europe. As CaPVs share 96–97% genetic similarity along the length of the entire genome and are difficult to distinguish using serological assays, simple, reliable and fast methods for diagnosis and species differentiation are crucial in cases of disease outbreak. The present study aimed to develop a field-applicable CaPV differentiation method. Nanopore technology was used for whole genome sequencing. A local database of complete CaPV genomes and partial sequences of three genes (RPO30, P32 and GPCR) was established for offline Basic Local Alignment Search Tool (BLAST). Specificities of 98.04% in whole genome and 97.86% in RPO30 gene runs were obtained among the three virus species, while other databases were less specific. The total run time was shortened to approximately 2 h. Functionality of the developed procedure was proved by samples with high host background sequences. Reliable differentiation options for the quality and capacity of hardware, and sample quality of suspected cases, were derived from these findings. The whole workflow can be performed rapidly with a mobile suitcase laboratory and mini-computer, allowing application at the point-of-need with limited resource settings. Full article

(This article belongs to the Special Issue Lumpy Skin Disease Control and Vaccines)

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30 pages, 9314 KiB

Open AccessArticle

Development of a Safe and Highly Efficient Inactivated Vaccine Candidate against Lumpy Skin Disease Virus

by Janika Wolff, Tom Moritz, Kore Schlottau, Donata Hoffmann, Martin Beer and Bernd Hoffmann

Vaccines 2021, 9(1), 4; https://doi.org/10.3390/vaccines9010004 - 23 Dec 2020

Cited by 37 | Viewed by 8781

Abstract

Capripox virus (CaPV)-induced diseases (lumpy skin disease, sheeppox, goatpox) are described as the most serious pox diseases of livestock animals, and therefore are listed as notifiable diseases under guidelines of the World Organisation for Animal Health (OIE). Until now, only live-attenuated vaccines are [...] Read more.

Capripox virus (CaPV)-induced diseases (lumpy skin disease, sheeppox, goatpox) are described as the most serious pox diseases of livestock animals, and therefore are listed as notifiable diseases under guidelines of the World Organisation for Animal Health (OIE). Until now, only live-attenuated vaccines are commercially available for the control of CaPV. Due to numerous potential problems after vaccination (e.g., loss of the disease-free status of the respective country, the possibility of vaccine virus shedding and transmission as well as the risk of recombination with field strains during natural outbreaks), the use of these vaccines must be considered carefully and is not recommended in CaPV-free countries. Therefore, innocuous and efficacious inactivated vaccines against CaPV would provide a great tool for control of these diseases. Unfortunately, most inactivated Capripox vaccines were reported as insufficient and protection seemed to be only short-lived. Nevertheless, a few studies dealing with inactivated vaccines against CaPV are published, giving evidence for good clinical protection against CaPV-infections. In our studies, a low molecular weight copolymer-adjuvanted vaccine formulation was able to induce sterile immunity in the respective animals after severe challenge infection. Our findings strongly support the possibility of useful inactivated vaccines against CaPV-infections, and indicate a marked impact of the chosen adjuvant for the level of protection. Full article

(This article belongs to the Special Issue Lumpy Skin Disease Control and Vaccines)

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Review

Jump to: Research

22 pages, 1373 KiB

Open AccessReview

Review: Vaccines and Vaccination against Lumpy Skin Disease

by Eeva Tuppurainen, Klaas Dietze, Janika Wolff, Hannes Bergmann, Daniel Beltran-Alcrudo, Anna Fahrion, Charles Euloge Lamien, Frank Busch, Carola Sauter-Louis, Franz J. Conraths, Kris De Clercq, Bernd Hoffmann and Sascha Knauf

Vaccines 2021, 9(10), 1136; https://doi.org/10.3390/vaccines9101136 - 6 Oct 2021

Cited by 88 | Viewed by 10241

Abstract

The geographical distribution of lumpy skin disease (LSD), an economically important cattle disease caused by a capripoxvirus, has reached an unprecedented extent. Vaccination is the only way to prevent the spread of the infection in endemic and newly affected regions. Yet, in the [...] Read more.

The geographical distribution of lumpy skin disease (LSD), an economically important cattle disease caused by a capripoxvirus, has reached an unprecedented extent. Vaccination is the only way to prevent the spread of the infection in endemic and newly affected regions. Yet, in the event of an outbreak, selection of the best vaccine is a major challenge for veterinary authorities and farmers. Decision makers need sound scientific information to support their decisions and subsequent actions. The available vaccine products vary in terms of quality, efficacy, safety, side effects, and price. The pros and cons of different types of live attenuated and inactivated vaccines, vaccination strategies, and associated risks are discussed. Seroconversion, which typically follows vaccination, places specific demands on the tools and methods used to evaluate the effectiveness of the LSD vaccination campaigns in the field. We aimed to give a comprehensive update on available vaccines and vaccination against LSD, to better prepare affected and at-risk countries to control LSD and ensure the safe trade of cattle. Full article

(This article belongs to the Special Issue Lumpy Skin Disease Control and Vaccines)

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