Plant-Based Vaccines: Production and Challenges

Laere, Erna; Ling, Anna Pick Kiong; Wong, Ying Pei; Koh, Rhun Yian; Lila, Mohd Azmi Mohd; Hussein, Sobri

doi:10.1155/2016/4928637

Cited by 57 publications

(88 citation statements)

References 81 publications

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“…However, due to the unstable availability of its natural source, A. annua, the supply and price of artemisinin fluctuated dramatically (37). Although engineering plants to produce pharmaceutical compounds remains challenging, products like Ebola vaccines have been successfully produced in transgenic tobacco (52).…”

Section: Methodsmentioning

confidence: 99%

Accumulation of high-value bioproducts in planta can improve the economics of advanced biofuels

Yang

Baral

Simmons

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Coproduction of high-value bioproducts at biorefineries is a key factor in making biofuels more cost-competitive. One strategy for generating coproducts is to directly engineer bioenergy crops to accumulate bioproducts in planta that can be fractionated and recovered at biorefineries. Here, we develop quantitative insights into the relationship between bioproduct market value and target accumulation rates by investigating a set of industrially relevant compounds already extracted from plant sources with a wide range of market prices and applications, including <$10/kg (limonene, latex, and polyhydroxybutyrate [PHB]), $10 to $100/kg (cannabidiol), and >$100/kg (artemisinin). These compounds are used to identify a range of mass fraction thresholds required to achieve net economic benefits for biorefineries and the additional amounts needed to reach a target $2.50/gal biofuel selling price, using cellulosic ethanol production as a test case. Bioproduct market prices and recovery costs determine the accumulation threshold; we find that moderate- to high-value compounds (i.e., cannabidiol and artemisinin) offer net economic benefits at accumulation rates of just 0.01% dry weight (dwt) to 0.02 dwt%. Lower-value compounds, including limonene, latex, and PHB, require at least an order-of-magnitude greater accumulation to overcome additional extraction and recovery costs (0.3 to 1.2 dwt%). We also find that a diversified approach is critical. For example, global artemisinin demand could be met with fewer than 10 biorefineries, while global demand for latex is equivalent to nearly 180 facilities. Our results provide a roadmap for future plant metabolic engineering efforts aimed at increasing the value derived from bioenergy crops.

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Section: Methodsmentioning

confidence: 99%

Accumulation of high-value bioproducts in planta can improve the economics of advanced biofuels

Yang

Baral

Simmons

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Despite human viruses, this system can be utilized for animal viruses which having an unbearable impact on poultry industries due to virus infections (61,63). Apart from that, this combinatorial siRNAs approach could replace as an alternate treatment especially for plant-based vaccines which encountering difficulties during production (64).…”

Section: Discussionmentioning

confidence: 99%

Multiple gene targeting siRNAs for down regulation of Immediate Early-2 (Ie2) and DNA polymerase genes mediated inhibition of novel rat Cytomegalovirus (strain All-03)

Balakrishnan

Abdullah

Bala

et al. 2020

Preprint

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Background Cytomegalovirus (CMV) is an opportunistic pathogen that causes severe complications in congenitally infected newborns and non-immunocompetent individuals. Developing an effective vaccine is a major public health priority and current drugs are fronting resistance and side effects on recipients. In the present study, with the aim of exploring new strategies to counteract CMV replication, several anti-CMV siRNAs targeting IE2 and DNA polymerase gene regions were characterized and used as in combinations for antiviral therapy. Methods The rat embryo fibroblast (REF) cells were transfected with multi siRNA before infecting with CMV strain ALL-03. Viral growth inhibition was measured by TCID50, cytopathic effect (CPE) and droplet digital PCR (ddPCR) while IE2 and DNA polymerase gene knockdown was determined by real-time PCR. Ganciclovir was deployed as a control to benchmark the efficacy of antiviral activities of respective individual siRNAs. Results There was no cytotoxicity encountered for all the combinations of siRNAs on REF cells analyzed by MTT colorimetric assay (P > 0.05). Cytopathic effects (CPE) in cells infected by RCMV ALL-03 developed significantly less and at much slower rate compared to control group. The expression of targeted genes was downregulated successfully resulted in significant reduction (P < 0.05) of viral mRNA and DNA copies (dpb + dpc: 79%, 68%; dpb + ie2b: 68%, 60%; dpb + dpc + ie2b: 48%, 42%). Flow cytometry analysis showed a greater percentage of viable and early apoptosis of combined siRNAs-treated cells compared to control group. Notably, the siRNAs targeting gene regions were sequenced and no any mutation was identified, thereby avoiding the formation of mutant with potential resistant viruses. Conclusions In conclusion. The study demonstrated a tremendous promise of innovative approach with the deployment of combined siRNAs targeting at several genes simultaneously with the aim to control CMV replication in host cells.

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“…Despite human viruses, this system can be utilized for animal viruses which having an unbearable impact on poultry industries due to virus infections (62,64). Apart from that, this combinatorial siRNAs approach could replace as an alternate treatment especially for plant-based vaccines which encountering difficulties during production (65).…”

Section: Knocking Down Efficiencymentioning

confidence: 99%

Multiple gene targeting siRNAs for down regulation of Immediate Early-2 (Ie2) and DNA polymerase genes mediated inhibition of novel rat Cytomegalovirus (strain All-03)

Balakrishnan

Abdullah

Bala

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Cytomegalovirus (CMV) is an opportunistic pathogen that causes severe complications in congenitally infected newborns and non-immunocompetent individuals. Developing an effective vaccine is a major public health priority and current drugs are fronting resistance and side effects on recipients. In the present study, with the aim of exploring new strategies to counteract CMV replication, several anti-CMV siRNAs targeting IE2 and DNA polymerase gene regions were characterized and used as in combinations for antiviral therapy. Methods: The rat embryo fibroblast (REF) cells were transfected with multi siRNA before infecting with CMV strain ALL-03. Viral growth inhibition was measured by tissue culture infectious dose (TCID50), cytopathic effect (CPE) and droplet digital PCR (ddPCR) while IE2 and DNA polymerase gene knockdown was determined by real-time PCR. Ganciclovir was deployed as a control to benchmark the efficacy of antiviral activities of respective individual siRNAs.Results: There was no significant cytotoxicity encountered for all the combinations of siRNAs on REF cells analyzed by MTT colorimetric assay (P>0.05). Cytopathic effects (CPE) in cells infected by RCMV ALL-03 had developed significantly less and at much slower rate compared to control group. The expression of targeted genes was downregulated successfully resulted in significant reduction (P<0.05) of viral mRNA and DNA copies (dpb+dpc: 79%, 68%; dpb+ie2b: 68%, 60%; dpb+dpc+ie2b: 48%, 42%). Flow cytometry analysis showed a greater percentage of viable and early apoptosis of combined siRNAs-treated cells compared to control group. Notably, the siRNAs targeting gene regions were sequenced and mutations were not encountered, thereby avoiding the formation of mutant with potential resistant viruses. Conclusions: In conclusion. The study demonstrated a tremendous promise of innovative approach with the deployment of combined siRNAs targeting at several genes simultaneously with the aim to control CMV replication in host cells.

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Plant-Based Vaccines: Production and Challenges

Cited by 57 publications

References 81 publications

Accumulation of high-value bioproducts in planta can improve the economics of advanced biofuels

Accumulation of high-value bioproducts in planta can improve the economics of advanced biofuels

Multiple gene targeting siRNAs for down regulation of Immediate Early-2 (Ie2) and DNA polymerase genes mediated inhibition of novel rat Cytomegalovirus (strain All-03)

Multiple gene targeting siRNAs for down regulation of Immediate Early-2 (Ie2) and DNA polymerase genes mediated inhibition of novel rat Cytomegalovirus (strain All-03)

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