Skip to main content
Erschienen in: Archives of Virology 3/2020

16.01.2020 | Original Article

Recombinant adenovirus carrying a core neutralizing epitope of porcine epidemic diarrhea virus and heat-labile enterotoxin B of Escherichia coli as a mucosal vaccine

verfasst von: Van Tan Do, Jisung Jang, Jeongho Park, Hoai Thu Dao, Kiju Kim, Tae-Wook Hahn

Erschienen in: Archives of Virology | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

Porcine epidemic diarrhea virus (PEDV) targets the intestinal mucosa in pigs. To protect against PEDV invasion, a mucosal vaccine is utilized effectively. In this study, we generated a recombinant adenovirus vaccine encoding the heat-labile enterotoxin B (LTB) and the core neutralizing epitope (COE) of PEDV (rAd-LTB-COE). The fusion protein LTB-COE was successfully expressed by the recombinant adenovirus in HEK293 cells, and the immunogenicity of the vaccine candidate was assessed in BALB/c mice and piglets. Three intramuscular or oral vaccinations with rAd-LTB-COE at two-week intervals induced robust humoral and mucosal immune responses. Moreover, a cell-mediated immune response was promoted in immunized mice, and the neutralizing antibody inhibited both the vaccine strain and the emerging PEDV isolate. Immunization experiments in piglets revealed that rAd-LTB-COE was immunogenic and induced good immune responses in piglets. Further studies are required to evaluate the efficacy of rAd-LTB-COE against a highly virulent PEDV challenge.
Literatur
1.
Zurück zum Zitat Pensaert M, de Bouck P (1978) A new coronavirus-like particle associated with diarrhea in swine. Arch Virol 58:243–247CrossRef Pensaert M, de Bouck P (1978) A new coronavirus-like particle associated with diarrhea in swine. Arch Virol 58:243–247CrossRef
2.
Zurück zum Zitat Lee C (2015) Porcine epidemic diarrhea virus: An emerging and re-emerging epizootic swine virus. Virol J 1:13–19 Lee C (2015) Porcine epidemic diarrhea virus: An emerging and re-emerging epizootic swine virus. Virol J 1:13–19
4.
Zurück zum Zitat Stevenson GW, Hoang H, Schwartz KJ, Burrough ER, Sun D, Madson D, Cooper VL, Pillatzki A, Gauger P, Schmitt BJ, Koster LG, Killian ML, Yoon KJ (2013) Emergence of Porcine epidemic diarrhea virus in the United States: clinical signs, lesions, and viral genomic sequences. J Vet Diagn Invest 25:649–654CrossRef Stevenson GW, Hoang H, Schwartz KJ, Burrough ER, Sun D, Madson D, Cooper VL, Pillatzki A, Gauger P, Schmitt BJ, Koster LG, Killian ML, Yoon KJ (2013) Emergence of Porcine epidemic diarrhea virus in the United States: clinical signs, lesions, and viral genomic sequences. J Vet Diagn Invest 25:649–654CrossRef
5.
Zurück zum Zitat Vlasova AN, Marthaler D, Wang Q, Culhane MR, Rossow KD, Rovira A, Collins J, Saif LJ (2014) Distinct characteristics and complex evolution of PEDV strains, North America, May 2013–February 2014. Emerg Infect Dis 20:1620–1628CrossRef Vlasova AN, Marthaler D, Wang Q, Culhane MR, Rossow KD, Rovira A, Collins J, Saif LJ (2014) Distinct characteristics and complex evolution of PEDV strains, North America, May 2013–February 2014. Emerg Infect Dis 20:1620–1628CrossRef
6.
Zurück zum Zitat Chang SH, Bae JL, Kang TJ, Kim J, Chung GH, Lim CW, Laude H, Yang MS, Jang YS (2002) Identification of the epitope region capable of inducing neutralizing antibodies against the porcine epidemic diarrhea virus. Mol Cells 14:295–299PubMed Chang SH, Bae JL, Kang TJ, Kim J, Chung GH, Lim CW, Laude H, Yang MS, Jang YS (2002) Identification of the epitope region capable of inducing neutralizing antibodies against the porcine epidemic diarrhea virus. Mol Cells 14:295–299PubMed
7.
Zurück zum Zitat Cruz DJM, Kim C, Shin H (2008) The GPRLQPY motif located at the carboxy-terminal of the spike protein induces antibodies that neutralize porcine epidemic diarrhea virus. Virus Res 132:192–196CrossRef Cruz DJM, Kim C, Shin H (2008) The GPRLQPY motif located at the carboxy-terminal of the spike protein induces antibodies that neutralize porcine epidemic diarrhea virus. Virus Res 132:192–196CrossRef
8.
Zurück zum Zitat Song D, Moon H, Kang B (2015) Porcine epidemic diarrhea: a review of current epidemiology and available vaccines. Clin Exp Vaccine Res 4:166–176CrossRef Song D, Moon H, Kang B (2015) Porcine epidemic diarrhea: a review of current epidemiology and available vaccines. Clin Exp Vaccine Res 4:166–176CrossRef
9.
Zurück zum Zitat Sun D, Feng L, Shi H, Chen J, Cui X, Chen H, Liu S, Tong Y, Wang Y, Tong G (2008) Identification of two novel B cell epitopes on porcine epidemic diarrhea virus spike protein. Vet Microbiol 131:73–81CrossRef Sun D, Feng L, Shi H, Chen J, Cui X, Chen H, Liu S, Tong Y, Wang Y, Tong G (2008) Identification of two novel B cell epitopes on porcine epidemic diarrhea virus spike protein. Vet Microbiol 131:73–81CrossRef
10.
Zurück zum Zitat Sun DB, Feng L, Shi HY, Chen JF, Liu SW, Chen HY, Wang YF (2007) Spike protein region (aa 636–789) of porcine epidemic diarrhea virus is essential for induction of neutralizing antibodies. Acta Virol 51:149–156PubMed Sun DB, Feng L, Shi HY, Chen JF, Liu SW, Chen HY, Wang YF (2007) Spike protein region (aa 636–789) of porcine epidemic diarrhea virus is essential for induction of neutralizing antibodies. Acta Virol 51:149–156PubMed
11.
Zurück zum Zitat Lavelle E, Sharif S, Thomas N, Holland J, Davis S (1995) The importance of gastrointestinal uptake of particles in the design of oral delivery systems. Adv Drug Deliv Rev 18:5–22CrossRef Lavelle E, Sharif S, Thomas N, Holland J, Davis S (1995) The importance of gastrointestinal uptake of particles in the design of oral delivery systems. Adv Drug Deliv Rev 18:5–22CrossRef
12.
Zurück zum Zitat Mestecky J, Michalek SZ, Moldoveanu Z, Russell MW (1997) Routes of immunization and antigen delivery systems for optimal mucosal immune responses in humans. Behring Inst Mitt 98:33–43 Mestecky J, Michalek SZ, Moldoveanu Z, Russell MW (1997) Routes of immunization and antigen delivery systems for optimal mucosal immune responses in humans. Behring Inst Mitt 98:33–43
13.
Zurück zum Zitat Kang T, Han S, Yang M, Jang Y (2006) Expression of synthetic neutralizing epitope of porcine epidemic diarrhea virus fused with synthetic B subunit of Escherichia coli heat-labile enterotoxin in tobacco plants. Protein Expr Purif 46:16–22CrossRef Kang T, Han S, Yang M, Jang Y (2006) Expression of synthetic neutralizing epitope of porcine epidemic diarrhea virus fused with synthetic B subunit of Escherichia coli heat-labile enterotoxin in tobacco plants. Protein Expr Purif 46:16–22CrossRef
14.
Zurück zum Zitat Spangler BD (1992) Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microbiol Rev 56:622–647CrossRef Spangler BD (1992) Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microbiol Rev 56:622–647CrossRef
15.
Zurück zum Zitat Bagdasarian MM, Nagai M, Frey J, Bagdasarian M (1999) Immunogenicity of Actinobacillus ApxIA toxin epitopes fused to the E. coli heat-labile enterotoxin B subunit. Vaccine 17:441–447CrossRef Bagdasarian MM, Nagai M, Frey J, Bagdasarian M (1999) Immunogenicity of Actinobacillus ApxIA toxin epitopes fused to the E. coli heat-labile enterotoxin B subunit. Vaccine 17:441–447CrossRef
17.
Zurück zum Zitat Alba R, Bosch A, Chillon M (2005) Gutless adenovirus: last-generation adenovirus for gene therapy. Gene Ther 12:18–27CrossRef Alba R, Bosch A, Chillon M (2005) Gutless adenovirus: last-generation adenovirus for gene therapy. Gene Ther 12:18–27CrossRef
18.
Zurück zum Zitat Douglas JT (2007) Adenoviral vectors for gene therapy. Mol Biotechnol 36:71–80CrossRef Douglas JT (2007) Adenoviral vectors for gene therapy. Mol Biotechnol 36:71–80CrossRef
19.
Zurück zum Zitat Wesley RD, Tang M, Lager KM (2004) Protection of weaned pigs by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of H3N2 swine influenza virus. Vaccine 22:3427–3434CrossRef Wesley RD, Tang M, Lager KM (2004) Protection of weaned pigs by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of H3N2 swine influenza virus. Vaccine 22:3427–3434CrossRef
20.
Zurück zum Zitat Berk AJ (1986) Adenovirus promoters and E1A transactivation. Annu Rev Genet 20:45–77CrossRef Berk AJ (1986) Adenovirus promoters and E1A transactivation. Annu Rev Genet 20:45–77CrossRef
21.
Zurück zum Zitat Ferguson A, Humphreys K, Croft N (1995) Technical report: results of immunological tests on faecal extracts are likely to be extremely misleading. Clin Exp Immunol 99:70–75CrossRef Ferguson A, Humphreys K, Croft N (1995) Technical report: results of immunological tests on faecal extracts are likely to be extremely misleading. Clin Exp Immunol 99:70–75CrossRef
22.
Zurück zum Zitat Lee S, Kim Y, Lee C (2015) Isolation and characterization of a Korean porcine epidemic diarrhea virus strain KNU-141112. Virus Res 208:215–224CrossRef Lee S, Kim Y, Lee C (2015) Isolation and characterization of a Korean porcine epidemic diarrhea virus strain KNU-141112. Virus Res 208:215–224CrossRef
23.
Zurück zum Zitat Huy N, Yang M, Kim T (2011) Expression of a cholera toxin B subunit-neutralizing epitope of the porcine epidemic diarrhea virus fusion gene in transgenic lettuce (Lactuca sativa L.). Mol Biotechnol 48:201–209CrossRef Huy N, Yang M, Kim T (2011) Expression of a cholera toxin B subunit-neutralizing epitope of the porcine epidemic diarrhea virus fusion gene in transgenic lettuce (Lactuca sativa L.). Mol Biotechnol 48:201–209CrossRef
24.
Zurück zum Zitat Kang T, Kang K, Kim J, Kwon T, Jang Y, Yang M (2004) High-level expression of the neutralizing epitope of porcine epidemic diarrhea virus by a tobacco mosaic virus-based vector. Protein Expr Purif 38:129–135CrossRef Kang T, Kang K, Kim J, Kwon T, Jang Y, Yang M (2004) High-level expression of the neutralizing epitope of porcine epidemic diarrhea virus by a tobacco mosaic virus-based vector. Protein Expr Purif 38:129–135CrossRef
25.
Zurück zum Zitat Lv C, Xiao Y, Li X, Tian K (2016) Porcine epidemic diarrhea virus: current insights. Virus Adapt Treat 8:1–12 Lv C, Xiao Y, Li X, Tian K (2016) Porcine epidemic diarrhea virus: current insights. Virus Adapt Treat 8:1–12
26.
Zurück zum Zitat Chen Q, Li G, Stasko J, Thomas JT, Stensland WR, Pillatzki AE, Gauger PC, Schwartz KJ, Madson D, Yoon KJ, Stevenson GW, Burrough ER, Harmon KM, Main RG, Zhang J (2014) Isolation and characterization of porcine epidemic diarrhea viruses associated with the 2013 disease outbreak among swine in the United States. J Clin Microbiol 52:234–243CrossRef Chen Q, Li G, Stasko J, Thomas JT, Stensland WR, Pillatzki AE, Gauger PC, Schwartz KJ, Madson D, Yoon KJ, Stevenson GW, Burrough ER, Harmon KM, Main RG, Zhang J (2014) Isolation and characterization of porcine epidemic diarrhea viruses associated with the 2013 disease outbreak among swine in the United States. J Clin Microbiol 52:234–243CrossRef
28.
Zurück zum Zitat Sun R, Cai R, Chen Y, Liang P, Chen D, Song C (2012) Outbreak of porcine epidemic diarrhea in suckling piglets, China. Emerg Infect Dis 18:161–163CrossRef Sun R, Cai R, Chen Y, Liang P, Chen D, Song C (2012) Outbreak of porcine epidemic diarrhea in suckling piglets, China. Emerg Infect Dis 18:161–163CrossRef
29.
Zurück zum Zitat Liu R, Wu L, Huang B, Huang J, Zhang Y, Ke M, Wang J, Tan W, Zhang R, Chen H (2005) Adenoviral expression of a truncated S1 subunit of SARS-CoV spike protein results in specific humoral immune responses against SARS-CoV in rats. Virus Res 112:24–31CrossRef Liu R, Wu L, Huang B, Huang J, Zhang Y, Ke M, Wang J, Tan W, Zhang R, Chen H (2005) Adenoviral expression of a truncated S1 subunit of SARS-CoV spike protein results in specific humoral immune responses against SARS-CoV in rats. Virus Res 112:24–31CrossRef
30.
Zurück zum Zitat Callebaut P, Enjuanes L, Pensaert M (1996) An adenovirus recombinant expressing the spike glycoprotein of porcine respiratory coronavirus is immunogenic in swine. J Gen Virol 77:309–313CrossRef Callebaut P, Enjuanes L, Pensaert M (1996) An adenovirus recombinant expressing the spike glycoprotein of porcine respiratory coronavirus is immunogenic in swine. J Gen Virol 77:309–313CrossRef
31.
Zurück zum Zitat Hashigucci K, Ogawa H, Ishidate T, Yamashita R, Kamiya H, Watanabe K, Hattori N, Sato T, Suzuki Y, Nagamine T (1996) Antibody responses in volunteers induced by nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit containing a trace amount of the holotoxin. Vaccine 14:113–119CrossRef Hashigucci K, Ogawa H, Ishidate T, Yamashita R, Kamiya H, Watanabe K, Hattori N, Sato T, Suzuki Y, Nagamine T (1996) Antibody responses in volunteers induced by nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit containing a trace amount of the holotoxin. Vaccine 14:113–119CrossRef
32.
Zurück zum Zitat Jawale CV, Lee JH (2014) Salmonella enterica serovar enteritidis ghosts carrying the Escherichia coli heat-labile enterotoxin B subunit are capable of inducing enhanced protective immune responses. Clin Vaccine Immunol 21:799–807CrossRef Jawale CV, Lee JH (2014) Salmonella enterica serovar enteritidis ghosts carrying the Escherichia coli heat-labile enterotoxin B subunit are capable of inducing enhanced protective immune responses. Clin Vaccine Immunol 21:799–807CrossRef
33.
Zurück zum Zitat Jeon BW, Jawale CV, Kim SH, Lee JH (2012) Attenuated Salmonella Gallinarum secreting an Escherichia coli heat-labile enterotoxin B subunit protein as an adjuvant for oral vaccination against fowl typhoid. Vet Immunol Immunopathol 150:149–160CrossRef Jeon BW, Jawale CV, Kim SH, Lee JH (2012) Attenuated Salmonella Gallinarum secreting an Escherichia coli heat-labile enterotoxin B subunit protein as an adjuvant for oral vaccination against fowl typhoid. Vet Immunol Immunopathol 150:149–160CrossRef
34.
Zurück zum Zitat Tamura S, Asanuma H, Tomita T, Komase K, Kawahara K, Danbara H, Hattori N, Watanabe K, Suzuki Y, Nagamine T (1994) Escherichia coli heat-labile enterotoxin B subunits supplemented with a trace amount of the holotoxin as an adjuvant for nasal influenza vaccine. Vaccine 12:1083–1089CrossRef Tamura S, Asanuma H, Tomita T, Komase K, Kawahara K, Danbara H, Hattori N, Watanabe K, Suzuki Y, Nagamine T (1994) Escherichia coli heat-labile enterotoxin B subunits supplemented with a trace amount of the holotoxin as an adjuvant for nasal influenza vaccine. Vaccine 12:1083–1089CrossRef
35.
Zurück zum Zitat Ge J, Liu D, Li Y (2012) Construction of recombinant lactobacilli expressing the core neutralizing epitope (COE) of porcine epidemic diarrhea virus and a fusion protein consisting of COE and Escherichia coli heat-labile enterotoxin B, and comparison of the immune responses by orogastric immunization. Can J Microbiol 58:1258–1267CrossRef Ge J, Liu D, Li Y (2012) Construction of recombinant lactobacilli expressing the core neutralizing epitope (COE) of porcine epidemic diarrhea virus and a fusion protein consisting of COE and Escherichia coli heat-labile enterotoxin B, and comparison of the immune responses by orogastric immunization. Can J Microbiol 58:1258–1267CrossRef
37.
Zurück zum Zitat Song D, Oh JS, Kang BK, Yang JS, Moon HJ, Yoo HS, Jang YS, Park BK (2007) Oral efficacy of Vero cell attenuated porcine epidemic diarrhea virus DR13 strain. Res Vet Sci 82:134–140CrossRef Song D, Oh JS, Kang BK, Yang JS, Moon HJ, Yoo HS, Jang YS, Park BK (2007) Oral efficacy of Vero cell attenuated porcine epidemic diarrhea virus DR13 strain. Res Vet Sci 82:134–140CrossRef
Metadaten
Titel
Recombinant adenovirus carrying a core neutralizing epitope of porcine epidemic diarrhea virus and heat-labile enterotoxin B of Escherichia coli as a mucosal vaccine
verfasst von
Van Tan Do
Jisung Jang
Jeongho Park
Hoai Thu Dao
Kiju Kim
Tae-Wook Hahn
Publikationsdatum
16.01.2020
Verlag
Springer Vienna
Erschienen in
Archives of Virology / Ausgabe 3/2020
Print ISSN: 0304-8608
Elektronische ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-019-04492-7

Weitere Artikel der Ausgabe 3/2020

Archives of Virology 3/2020 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhöhte Mortalität bei postpartalem Brustkrebs

07.05.2024 Mammakarzinom Nachrichten

Auch für Trägerinnen von BRCA-Varianten gilt: Erkranken sie fünf bis zehn Jahre nach der letzten Schwangerschaft an Brustkrebs, ist das Sterberisiko besonders hoch.

Hypertherme Chemotherapie bietet Chance auf Blasenerhalt

07.05.2024 Harnblasenkarzinom Nachrichten

Eine hypertherme intravesikale Chemotherapie mit Mitomycin kann für Patienten mit hochriskantem nicht muskelinvasivem Blasenkrebs eine Alternative zur radikalen Zystektomie darstellen. Kölner Urologen berichten über ihre Erfahrungen.

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Medizinstudium Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.

Vorhofflimmern bei Jüngeren gefährlicher als gedacht

06.05.2024 Vorhofflimmern Nachrichten

Immer mehr jüngere Menschen leiden unter Vorhofflimmern. Betroffene unter 65 Jahren haben viele Risikofaktoren und ein signifikant erhöhtes Sterberisiko verglichen mit Gleichaltrigen ohne die Erkrankung.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.