The Effect of Plant Tissue and Vaccine Formulation on the Oral Immunogenicity of a Model Plant-Made Antigen in Sheep

Pelosi, Assunta; Piedrafita, David; Guzman, Giorgio De; Shepherd, Robert; Hamill, John D.; Meeusen, Elza Nicole Theresia; Walmsley, Amanda Maree

doi:10.1371/journal.pone.0052907

Cited by 19 publications

(7 citation statements)

References 36 publications

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“…However, some important issue to consider are how the differences in the ruminant gut might affect the vaccine and whether the plant-bioencapsulated antigen would still be viable once the plant material reaches the intestine. Although there are numerous studies reporting immunogenicity of orally delivered plant-made vaccines in humans and small animal models, only a few have successfully demonstrated their efficacy in ruminants [70–74]. The concept of transgenic plant-based vaccines has been successfully employed by Pelosi et al in their study on antigen-specific antibody responses against a model antigen (the B subunit of the heat labile toxin of enterotoxigenic E .…”

Section: Discussionmentioning

confidence: 99%

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Immune response of rats vaccinated orally with various plant-expressed recombinant cysteine proteinase constructs when challenged with Fasciola hepatica metacercariae

et al. 2017

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BackgroundCysteine proteinases of Fasciola hepatica are important candidates for vaccine antigens because of their role in fluke biology and host-parasite relationships. In our previous experiments, we found that a recombinant cysteine proteinase cloned from adult F. hepatica (CPFhW) can protect rats against liver fluke infections when it is administered intramuscularly or intranasally in the form of cDNA. We also observed considerable protection upon challenge following mucosal vaccination with inclusion bodies containing recombinant CPFhW produced in Escherichia coli.In this study, we explore oral vaccination, which may be the desired method of delivery and is potentially capable of preventing infections at the site of helminth entry. To provide antigen encapsulation and to protect the vaccine antigen from degradation in the intestinal tract, transgenic plant-based systems are used.MethodologyIn the present study, we aimed to evaluate the protective ability of mucosal vaccinations of 12-week-old rats with CPFhW produced in a transgenic-plant-based system. To avoid inducing tolerance and to maximise the immune response induced by oral immunisation, we used the hepatitis B virus (HBV) core protein (HBcAg) as a carrier. Animals were immunised with two doses of the antigen and challenged with 25 or 30 metacercariae of F. hepatica.ConclusionsWe obtained substantial protection after oral administration of the plant-produced hybrids of CPFhW and HBcAg. The highest level of protection (65.4%) was observed in animals immunised with transgenic plants expressing the mature CPFhW enzyme flanked by Gly-rich linkers and inserted into c/e1 epitope of truncated HBcAg. The immunised rats showed clear IgG1 and IgM responses to CPFhW for 4 consecutive weeks after the challenge.

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Section: Discussionmentioning

confidence: 99%

“…The delivery resulted in antigen-specific immune responses in mucosal secretions of the abomasum, small intestine and mesenteric lymph nodes. These findings suggest that the orally administered plant-bioencapsulated antigens are still viable after the passage through the rumen and elicit mucosal and systemic immune responses in sheep [70]. …”

Section: Discussionmentioning

confidence: 99%

Immune response of rats vaccinated orally with various plant-expressed recombinant cysteine proteinase constructs when challenged with Fasciola hepatica metacercariae

et al. 2017

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“…While tomato yielded the least amount of antigen overall, the antigen accumulation was reasonable when compared to other plant systems producing LTB [57–59]. Unfortunately, oral delivery of vaccine antigens within hairy root tissue has proven less efficient than other plant tissues perhaps due to the cell walls being too thick and not releasing enough antigen from the cells at optimal locations throughout the digestive tract [60,61]. Secretion or purification of recombinant proteins from hairy roots may prove to be the more realistic approach for this platform.…”

Section: Available Molecular Tools For Protein Production In Solanmentioning

confidence: 99%

Production of Pharmaceutical Proteins in Solanaceae Food Crops

Rigano

Guzman

Walmsley

et al. 2013

IJMS

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The benefits of increased safety and cost-effectiveness make vegetable crops appropriate systems for the production and delivery of pharmaceutical proteins. In particular, Solanaceae edible crops could be inexpensive biofactories for oral vaccines and other pharmaceutical proteins that can be ingested as minimally processed extracts or as partially purified products. The field of crop plant biotechnology is advancing rapidly due to novel developments in genetic and genomic tools being made available today for the scientific community. In this review, we briefly summarize data now available regarding genomic resources for the Solanaceae family. In addition, we describe novel strategies developed for the expression of foreign proteins in vegetable crops and the utilization of these techniques to manufacture pharmaceutical proteins.

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“…Such a scenario may explain why low antibody levels were reported in pre-challenge period in our study. Further, also other studies have demonstrated plant-made vaccine efficacy in ruminating animals and have reported specific mucosal and systemic responses ( 44 – 47 ). Thus, oral delivery of plant-made vaccines is a viable alternative in ruminant vaccination.…”

Section: Discussionmentioning

confidence: 93%

A Preliminary Study of a Lettuce-Based Edible Vaccine Expressing the Cysteine Proteinase of Fasciola hepatica for Fasciolosis Control in Livestock

et al. 2018

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Oral vaccination with edible vaccines is one of the most promising approaches in modern vaccinology. Edible vaccines are an alternative to conventional vaccines, which are typically delivered by injection. Here, freeze-dried transgenic lettuce expressing the cysteine proteinase of the trematode Fasciola hepatica (CPFhW) was used to orally vaccinate cattle and sheep against fasciolosis, which is the most important trematode disease due to the parasite's global distribution, wide spectrum of host species and significant economic losses of farmers. In the study, goals such as reducing the intensity of infection, liver damage and F. hepatica fecundity were achieved. Moreover, we demonstrated that the host sex influenced the outcome of infection following vaccination, with female calves and male lambs showing better protection than their counterparts. Since differences occurred following vaccination and infection, different immunization strategies should be considered for different sexes and host species when developing new control methods. The results of the present study highlight the potential of oral vaccination with plant-made and plant-delivered vaccines for F. hepatica infection control.

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The Effect of Plant Tissue and Vaccine Formulation on the Oral Immunogenicity of a Model Plant-Made Antigen in Sheep

Cited by 19 publications

References 36 publications

Immune response of rats vaccinated orally with various plant-expressed recombinant cysteine proteinase constructs when challenged with Fasciola hepatica metacercariae

Immune response of rats vaccinated orally with various plant-expressed recombinant cysteine proteinase constructs when challenged with Fasciola hepatica metacercariae

Production of Pharmaceutical Proteins in Solanaceae Food Crops

A Preliminary Study of a Lettuce-Based Edible Vaccine Expressing the Cysteine Proteinase of Fasciola hepatica for Fasciolosis Control in Livestock

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