Humoral and cell-mediated immune responses to plant-produced African horse sickness virus VP7 quasi-crystals.
Abstract: African horse sickness (AHS) is a devastating viral disease affecting equines and has resulted in many disastrous epizootics. To date, no successful therapeutic treatment exists for AHS, and commercially used live-attenuated vaccines have various undesirable side effects. Previous studies have shown that mice inoculated with insoluble African horse sickness virus (AHSV) VP7 crystals are protected from live challenge with a lethal dose of AHSV. This study investigates the humoral and cell-mediated immune responses in guinea-pigs to a safer monovalent vaccine alternative based on AHSV-5 VP7 quasi-crystals produced in plants. Guinea-pigs received prime- and boost-inoculations of between 10 and 50 μg of purified plant-produced AHSV VP7. Western immunoblot analysis of the humoral response showed stimulation of high titres of anti-VP7 antibodies 28 days after the boost-inoculation in sera from three of the five experimental animals. In addition, RNA-seq transcriptome profiling of guinea-pig spleen-derived RNA highlighted thirty significantly (q ≤ 0.05) differentially expressed genes involved in innate and adaptive immunity. Differential expression of genes involved in Th1, Th2 and Th17 cell differentiation suggest a cell-mediated immune response to AHSV-5 VP7. Upregulation of several important cytokines and cytokine receptors were noted, including TNFSF14, CX3CR1, IFNLR1 and IL17RA. Upregulation of IL17RA suggests a Th17 response which has been reported as a key component in AHSV immunity. While further investigation is needed to validate these findings, these results suggest that AHSV-5 VP7 quasi-crystals produced in N. benthamiana are immunogenic and induce both humoral and cell-mediated responses.
Copyright © 2021 Elsevier B.V. All rights reserved.
Publication Date: 2021-01-06 PubMed ID: 33421520DOI: 10.1016/j.virusres.2020.198284Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research involves investigating the immune response to a monovalent vaccine derived from African horse sickness virus VP7 quasi-crystals in guinea-pigs. It found that the vaccine stimulates significant antibody response and causes changes in genes associated with innate and adaptive immunity.
Background
- The study is targeted at African horse sickness (AHS), a deadly disease affecting equines, with currently no effective therapeutic treatment. It has caused disastrous epidemics.
- Existing vaccinations based on live-attenuated vaccines have several adverse side effects.
- Past studies have demonstrated that mice vaccinated with insoluble AHS virus (AHSV) VP7 crystals showed resistant to lethal doses of AHSV.
Purpose and Method
- The research aims to study the immune responses in guinea-pigs to a safer alternative vaccine made from AHSV-5 VP7 quasi-crystals developed in plants.
- Guinea pigs were administered prime- and boost-inoculations of between 10 and 50 μg of the plant-produced AHSV VP7.
- Western immunoblot analysis was used to assess the subsequent antibody response.
- RNA-seq transcriptome profiling was used to study associated gene expression changes in spleen-derived RNA in guinea pigs.
Findings
- High levels of anti-VP7 antibodies were produced in three of the five guinea-pigs tested 28 days post-boost inoculation.
- RNA profiling identified 30 significantly differentially expressed genes associated with innate and adaptive immunity.
- Alterations in the expression of Th1, Th2 and Th17 cell differentiation genes were observed, supporting potential cell-mediated immunity response to AHSV-5 VP7.
- Key cytokines and cytokine receptors such as TNFSF14, CX3CR1, IFNLR1 and IL17RA were upregulated.
- The increased level of IL17RA, indicating Th17 response, points to it being an essential element in AHSV immunity.
Conclusion
- The research suggests that plant-produced AHSV-5 VP7 quasi-crystals have immunogenic properties, provoking both humoral and cell-mediated responses.
- Further investigation is needed to confirm these findings.
Cite This Article
APA
Fearon SH, Dennis SJ, Hitzeroth II, Rybicki EP, Meyers AE.
(2021).
Humoral and cell-mediated immune responses to plant-produced African horse sickness virus VP7 quasi-crystals.
Virus Res, 294, 198284.
https://doi.org/10.1016/j.virusres.2020.198284 Publication
Researcher Affiliations
- Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Rondebosch, Cape Town 7700, South Africa.
- Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Rondebosch, Cape Town 7700, South Africa.
- Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Rondebosch, Cape Town 7700, South Africa.
- Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Rondebosch, Cape Town 7700, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Rondebosch, Cape Town 7700, South Africa.
- Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Rondebosch, Cape Town 7700, South Africa. Electronic address: ann.meyers@uct.ac.za.
MeSH Terms
- African Horse Sickness / prevention & control
- African Horse Sickness Virus / genetics
- Animals
- Antibodies, Viral
- Guinea Pigs
- Horses
- Immunity
- Mice
- Receptors, Interferon
- Vaccines, Attenuated
- Viral Vaccines
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