Design of a multi-epitope protein as a subunit vaccine against lumpy skin disease using an immunoinformatics approach

Kar, Prajna Parimita; Araveti, Prasanna Babu; Kuriakose, Akshay; Srivastava, Anand

doi:10.1038/s41598-022-23272-z

Cited by 12 publications

(13 citation statements)

References 65 publications

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“…There is some hesitancy to introduce live attenuated LSDV vaccines into areas with no LSDV, not only for safety considerations, but also because of the impact on the “disease free status” of the country [ 85 ]. Therefore, there has been an effort to develop inactivated and subunit vaccines [ 86 , 87 ]. As a result, developments have been made to produce safer LSDV vaccines and to further improve their immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

Lumpy Skin Disease—An Emerging Cattle Disease in Europe and Asia

2023

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Lumpy skin disease virus (LSDV) is a member of the Capripoxvirus genus, mainly infecting cattle and buffalo, which until relatively recently was only endemic in parts of Africa and then spread to the Middle East and lately Europe and Asia. Lumpy skin disease (LSD) is a notifiable disease with a serious impact on the beef industry as it causes mortality of up to 10% and has impacts on milk and meat production, as well as fertility. The close serological relationship between LSDV, goat poxvirus (GTPV) and sheep poxvirus (SPPV) has led to live attenuated GTPV and SPPV vaccines being used to protect against LSD in some countries. There is evidence that the SPPV vaccine does not protect from LSD as well as the GTPV and LSDV vaccines. One of the LSD vaccines used in Eastern Europe was found to be a combination of different Capripoxviruses, and a series of recombination events in the manufacturing process resulted in cattle being vaccinated with a range of recombinant LSDVs resulting in virulent LSDV which spread throughout Asia. It is likely that LSD will become endemic throughout Asia as it will be very challenging to control the spread of the virus without widespread vaccination.

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Section: Introductionmentioning

confidence: 99%

Lumpy Skin Disease—An Emerging Cattle Disease in Europe and Asia

2023

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“…Quite recently, Kar et al. ( 40 ) predicted the 3-D structure of bovine TLR2 as a reliable computational tool. However, the structures of bovine TLR1 and TLR6 are unavailable.…”

Section: Discussionmentioning

confidence: 99%

Sperm activate TLR2/TLR1 heterodimerization to induce a weak proinflammatory response in the bovine uterus

et al. 2023

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Toll-like receptor 2 (TLR2) signaling pathway is involved in the sperm-triggered uterine inflammatory response at insemination, but its precise mechanism at molecular-level remains unknown. According to the ligand specificity, TLR2 forms a heterodimer with TLR1 or TLR6 as an initial step to mediate intracellular signaling, leading to a specific type of immune response. Hence, the present study aimed to identify the active TLR2 heterodimer (TLR2/1 or TLR2/6) that is involved in sperm-uterine immune crosstalk in bovine using various models. First, in-vitro (bovine endometrial epithelial cells, BEECs) and ex-vivo (bovine uterine explant) models were employed to test different TLR2 dimerization pathways in endometrial epithelia after exposure to sperm or TLR2 agonists; PAM3 (TLR2/1 agonist), and PAM2 (TLR2/6 agonist). Additionally, in-silico approaches were performed to confirm the dimer stability using de novo protein structure prediction model for bovine TLRs. The in-vitro approach revealed that sperm triggered the mRNA and protein expression of TLR1 and TLR2 but not TLR6 in BEECs. Moreover, this model disclosed that activation of TLR2/6 heterodimer, triggers a much stronger inflammatory response than TLR2/1 and sperm in bovine uterine epithelia. In the ex-vivo model that mimics the intact uterine tissue at insemination, sperm also induced the protein expression of both TLR1 and TLR2, but not TLR6, in bovine endometrium, particularly in uterine glands. Importantly, PAM3 and sperm induced similar and low mRNA expression of pro-inflammatory cytokines and TNFA protein to a lesser extent than PAM2 in endometrial epithelia. This implied that sperm might trigger a weak inflammatory response via TLR2/TLR1 activation which is similar to that of PAM3. Additionally, the in-silico analyses showed that the existence of bridging ligands is essential for heterodimer stability in bovine TLR2 with either TLR1 or TLR6. Altogether, the present findings revealed that sperm utilize TLR2/1, but not TLR2/6, heterodimerization to trigger a weak physiological inflammatory response in the bovine uterus. This might be the way to remove excess dead sperm remaining in the uterine lumen without tissue damage for providing an ideal uterine environment for early embryo reception and implantation.

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“…The first successful instance of mRNA therapeutics was reported in 1990, and since then effective and versatile mRNA vaccines have been developed against HIV-1, Zika, rabies, influenza virus, and other viruses [ 47 , 48 , 49 , 50 , 51 ]. LSDV surface proteins were prioritized to predict potential T- and B-cell epitopes for designing a multi-peptide-based vaccine construct capable of eliciting a strong CD4+ and CD8+ T-cell-associated immune response [ 52 ]. Kar et al (2022) predicted a vaccine model based on MHC-I and B-cell epitopes based on limited protein sequences of the LSDV.…”

Section: Discussionmentioning

confidence: 99%

Annotation of Potential Vaccine Targets and Designing of mRNA-Based Multi-Epitope Vaccine against Lumpy Skin Disease Virus via Reverse Vaccinology and Agent-Based Modeling

et al. 2023

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Lumpy skin disease is a fatal emerging disease of cattle, which has started to gain extensive attention due to its rapid incursions across the globe. The disease epidemic causes economic loss and cattle morbidity. Currently, there are no specific treatments and safe vaccines against the lumpy skin disease virus (LSDV) to halt the spread of the disease. The current study uses genome-scan vaccinomics analyses to prioritize promiscuous vaccine candidate proteins of the LSDV. These proteins were subjected to top-ranked B- and T-cell epitope prediction based on their antigenicity, allergenicity, and toxicity values. The shortlisted epitopes were connected using appropriate linkers and adjuvant sequences to design multi-epitope vaccine constructs. Three vaccine constructs were prioritized based on their immunological and physicochemical properties. The model constructs were back-translated to nucleotide sequences and codons were optimized. The Kozak sequence with a start codon along with MITD, tPA, Goblin 5′, 3′ UTRs, and a poly(A) tail sequences were added to design a stable and highly immunogenic mRNA vaccine. Molecular docking followed by MD simulation analysis predicted significant binding affinity and stability of LSDV-V2 construct within bovine immune receptors and predicted it to be the top-ranked candidate to stimulate the humeral and cellular immunogenic responses. Furthermore, in silico restriction cloning predicted feasible gene expression of the LSDV-V2 construct in a bacterial expression vector. It could prove worthwhile to validate the predicted vaccine models experimentally and clinically against LSDV.

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Design of a multi-epitope protein as a subunit vaccine against lumpy skin disease using an immunoinformatics approach

Cited by 12 publications

References 65 publications

Lumpy Skin Disease—An Emerging Cattle Disease in Europe and Asia

Lumpy Skin Disease—An Emerging Cattle Disease in Europe and Asia

Sperm activate TLR2/TLR1 heterodimerization to induce a weak proinflammatory response in the bovine uterus

Annotation of Potential Vaccine Targets and Designing of mRNA-Based Multi-Epitope Vaccine against Lumpy Skin Disease Virus via Reverse Vaccinology and Agent-Based Modeling

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