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      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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          Abstract

          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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          Most cited references54

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          Immunology of gut mucosal vaccines.

          Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. © 2010 John Wiley & Sons A/S.
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            Immunogenicity in humans of an edible vaccine for hepatitis B.

            A double-blind placebo-controlled clinical trial evaluated the immunogenicity of hepatitis B surface antigen (HBsAg) expressed in potatoes and delivered orally to previously vaccinated individuals. The potatoes accumulated HBsAg at approximately 8.5 microg/g of potato tuber, and doses of 100 g of tuber were administered by ingestion. The correlate of protection for hepatitis B virus, a nonenteric pathogen, is blood serum antibody titers against HBsAg. After volunteers ate uncooked potatoes, serum anti-HBsAg titers increased in 10 of 16 volunteers (62.5%) who ate three doses of potatoes; in 9 of 17 volunteers (52.9%) who ate two doses of transgenic potatoes; and in none of the volunteers who ate nontransgenic potatoes. These results were achieved without the coadministration of a mucosal adjuvant or the need for buffering stomach pH. We conclude that a plant-derived orally delivered vaccine for prevention of hepatitis B virus should be considered as a viable component of a global immunization program.
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              Fasciola hepatica vaccine: We may not be there yet but we’re on the right road

              Major advances have been made in identifying potential vaccine molecules for the control of fasciolosis in livestock but we have yet to reach the level of efficacy required for commercialisation. The pathogenesis of fasciolosis is associated with liver damage that is inflicted by migrating and feeding immature flukes as well as host inflammatory immune responses to parasite-secreted molecules and tissue damage alarm signals. Immune suppression/modulation by the parasites prevents the development of protective immune responses as evidenced by the lack of immunity observed in naturally and experimentally infected animals. In our opinion, future efforts need to focus on understanding how parasites invade and penetrate the tissues of their hosts and how they potentiate and control the ensuing immune responses, particularly in the first days of infection. Emerging ‘omics’ data employed in an unbiased approach are helping us understand liver fluke biology and, in parallel with new immunological data, to identify molecules that are essential to parasite development and accessible to vaccine-induced immune responses.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                13 November 2018
                2018
                : 9
                : 2592
                Affiliations
                [1] 1Polish Academy of Sciences, Witold Stefanski Institute of Parasitology , Warsaw, Poland
                [2] 2Polish Academy of Sciences, Institute of Bioorganic Chemistry , Poznan, Poland
                [3] 3Department of Bioengineering, Institute of Biotechnology and Antibiotics , Warsaw, Poland
                Author notes

                Edited by: Rashika El Ridi, Cairo University, Egypt

                Reviewed by: Pornanan Kueakhai, Burapha University, Thailand; Fernando L. García Carreño, Centro de Investigación Biológica del Noreste (CIBNOR), Mexico; Ileana Corvo, Universidad de la República, Uruguay

                *Correspondence: Agnieszka Wesołowska a.wesolowska@ 123456twarda.pan.pl

                This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology

                †Present Address: Monika Kozak Ljunggren, Centre for Biomedical Resources, Linköping University, Linköping, Sweden

                Article
                10.3389/fimmu.2018.02592
                6244665
                30483259
                4a1d60f7-c255-42de-b502-058cc989eb5d
                Copyright © 2018 Wesołowska, Kozak Ljunggren, Jedlina, Basałaj, Legocki, Wedrychowicz and Kesik-Brodacka.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 September 2018
                : 22 October 2018
                Page count
                Figures: 4, Tables: 4, Equations: 0, References: 56, Pages: 11, Words: 8124
                Categories
                Immunology
                Original Research

                Immunology
                lettuce-derived vaccine,oral delivery,fasciola hepatica,ruminants,cysteine protease
                Immunology
                lettuce-derived vaccine, oral delivery, fasciola hepatica, ruminants, cysteine protease

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