Cytotoxic T lymphocyte epitopes identified from a contemporary strain of porcine reproductive and respiratory syndrome virus enhance CD4+CD8+ T, CD8+ T, and γδ T cell responses

Cao, Qian M.; Tian, Debin; Heffron, C. Lynn; Subramaniam, Sakthivel; Opriessnig, Tanja; Foss, Dennis L.; Calvert, Jay G.; Meng, Xiang‐Jin

doi:10.1016/j.virol.2019.09.006

Cited by 16 publications

(27 citation statements)

References 49 publications

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“…These data support the further evaluation of these vectors for efficacy against NiV and potentially further development as DIVA vaccines which could be prophylactically or reactively to prevent/control NiV outbreaks. The prodigious T cell responses demonstrated with the BoHV-4 vectors also supports their evaluation in the delivery of antigens from other porcine viruses for which T cells are thought to play an important role in protection of, e.g., African swine fever [85,86] and porcine reproductive and respiratory syndrome viruses [87,88].…”

Section: Discussionmentioning

confidence: 73%

Bovine Herpesvirus-4-Vectored Delivery of Nipah Virus Glycoproteins Enhances T Cell Immunogenicity in Pigs

et al. 2020

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Nipah virus (NiV) is an emergent pathogen capable of causing acute respiratory illness and fatal encephalitis in pigs and humans. A high fatality rate and broad host tropism makes NiV a serious public and animal health concern. There is therefore an urgent need for a NiV vaccines to protect animals and humans. In this study we investigated the immunogenicity of bovine herpesvirus (BoHV-4) vectors expressing either NiV attachment (G) or fusion (F) glycoproteins, BoHV-4-A-CMV-NiV-GΔTK or BoHV-4-A-CMV-NiV-FΔTK, respectively in pigs. The vaccines were benchmarked against a canarypox (ALVAC) vector expressing NiV G, previously demonstrated to induce protective immunity in pigs. Both BoHV-4 vectors induced robust antigen-specific antibody responses. BoHV-4-A-CMV-NiV-GΔTK stimulated NiV-neutralizing antibody titers comparable to ALVAC NiV G and greater than those induced by BoHV-4-A-CMV-NiV-FΔTK. In contrast, only BoHV-4-A-CMV-NiV-FΔTK immunized pigs had antibodies capable of significantly neutralizing NiV G and F-mediated cell fusion. All three vectored vaccines evoked antigen-specific CD4 and CD8 T cell responses, which were particularly strong in BoHV-4-A-CMV-NiV-GΔTK immunized pigs and to a lesser extent BoHV-4-A-CMV-NiV-FΔTK. These findings emphasize the potential of BoHV-4 vectors for inducing antibody and cell-mediated immunity in pigs and provide a solid basis for the further evaluation of these vectored NiV vaccine candidates.

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Section: Discussionmentioning

confidence: 73%

Bovine Herpesvirus-4-Vectored Delivery of Nipah Virus Glycoproteins Enhances T Cell Immunogenicity in Pigs

et al. 2020

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“…In this study, five RMA-S stable cell lines were generated, each expressing a particular SLA I allele. The SLA I alleles were carefully selected on the basis of SLA I allele distribution in US commercial swine farms from our earlier study [25]. We demonstrated that SLA I alleles SLA1*0401, SLA1*0801 and SLA2*0401 were significantly expressed on the surface of RMA-S cells in the absence of exogenous peptides at 27 °C as compared to the same cells incubated at 37 °C ().…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, a broader and more comprehensive coverage of PRRSV antigenic proteins should be considered in future studies. Another possible reason for the poor efficacy is that the piglets that we used in this study may have shown a large variation of the SLA profile compared to the SLA profile we previously identified from swine herds in the USA [25]. Although in this present study we used piglets from the same herd from which the SLA profile of pigs was obtained in our previous study, and the T cell epitopes for vaccine designs were selected based on highly prevalent SLA alleles from the swine herds, large variation of SLA alleles may occur among different batches of pigs.…”

Section: Discussionmentioning

confidence: 99%

“…This server looks at each possible 9-mer and generates a score based on a weighted average of: (1) predicted binding affinity, (2) predicted proteasome cleavage efficiency and (3) predicted TAP transport efficiency. After removing 9-mers that included 1 or more cysteine residues, the 30 highest ranking T cell epitope peptides were selected for each of 5 highly prevalent SLA I alleles (SLA1*0401, SLA1*0801, SLA2*0401, SLA2*0202 and SLA3*0502) in commercial swine herds in the USA, including the same swine herd from which the pigs were used for this present study [25]. The selected peptides were synthesized commercially (Genscript) with at least 95 % purity and the peptide stocks were made in sterile water or DMSO according to the manufacturer determined solubility data.…”

Section: Methodsmentioning

confidence: 99%

“…A total of 30 PRRSV-negative piglets at 4 weeks of age were randomly divided into 3 groups of 10 piglets per group housed in separate rooms. The piglets were purchased from the same swine herd from which the SLA allele profile of the pigs had previously been determined and characterized, and the highly prevalent SLA alleles in our previous study were used to select T cell epitope peptides in this present study [25]. Piglets in each group were intramuscularly injected into neck muscles with the recombinant adenovirus expressing poly-T cell epitope antigen or LacZ as control ().…”

Section: Methodsmentioning

confidence: 99%

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Construction and efficacy evaluation of novel swine leukocyte antigen (SLA) class I and class II allele-specific poly-T cell epitope vaccines against porcine reproductive and respiratory syndrome virus

Tian

Subramaniam

Heffron

et al. 2020

Journal of General Virology

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Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically important global swine disease. Here we report the development of subunit PRRSV-2 vaccines by expressing swine leucocyte antigen (SLA) class I and class II allele-specific epitope antigens in a robust adenovirus vector. SLA I-specific CD8 and SLA II-specific CD4 T cell epitopes of PRRSV-2 NADC20 were predicted in silico. Stable murine leukaemia cell lines (RMA-S), which are TAP-deficient and lacking endogenous class I epitope loading, were established to express different SLA I alleles. The binding stability of PRRSV T cell epitope peptides with SLA I alleles expressed on RMA-S cells was characterized. Two PRRSV poly-T cell epitope peptides were designed. NADC20-PP1 included 39 class I epitopes, consisting of 8 top-ranked epitopes specific to each of 5 SLA I alleles, and fused to 5 class II epitopes specific to SLA II alleles. NADC20-PP2, a subset of PP1, included two top-ranked class I epitopes specific to each of the five SLA I alleles. Two vaccine candidates, Ad-NADC20-PP1 and Ad-NADC20-PP2, were constructed by expressing the polytope peptides in a replication-incompetent human adenovirus 5 vector. A vaccination and challenge study in 30 piglets showed that animals vaccinated with the vaccines had numerically lower gross and histopathology lung lesions, and numerically lower PRRSV RNA loads in lung and serum after challenge compared to the controls, although there was no statistical significance. The results suggested that the Ad-NADC20-PP1 and Ad-NADC20-PP2 vaccines provided little or no protection, further highlighting the tremendous challenges faced in developing an effective subunit PRRSV-2 vaccine.

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Identification of potential SLA-I-specific T-cell epitopes within the structural proteins of porcine deltacoronavirus

Wen

Chen

Yang

et al. 2023

International Journal of Biological Macromolecules

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Cytotoxic T lymphocyte epitopes identified from a contemporary strain of porcine reproductive and respiratory syndrome virus enhance CD4+CD8+ T, CD8+ T, and γδ T cell responses

Cited by 16 publications

References 49 publications

Bovine Herpesvirus-4-Vectored Delivery of Nipah Virus Glycoproteins Enhances T Cell Immunogenicity in Pigs

Bovine Herpesvirus-4-Vectored Delivery of Nipah Virus Glycoproteins Enhances T Cell Immunogenicity in Pigs

Construction and efficacy evaluation of novel swine leukocyte antigen (SLA) class I and class II allele-specific poly-T cell epitope vaccines against porcine reproductive and respiratory syndrome virus

Identification of potential SLA-I-specific T-cell epitopes within the structural proteins of porcine deltacoronavirus

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