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J Virol. Jun 1996; 70(6): 3770–3780.
PMCID: PMC190253

Tropism of human adenovirus type 5-based vectors in swine and their ability to protect against transmissible gastroenteritis coronavirus.

Abstract

The infection of epithelia] swine testicle and intestinal porcine epithelial (IPEC-1) cell lines by adenovirus type 5 (Ad5) has been studied in vitro by using an Ad5-luciferase recombinant containing the firefly luciferase gene as a reporter. Porcine cell lines supported Ad5 replication, showing virus titers, kinetics of virus production, and luciferase expression levels similar to those obtained in human 293 cells, which constitutively express the 5'-end 11% of the Ad5 genome. The tropism of Ad5-based vectors in swine and its ability to induce an efficient immune response against heterologous antigens expressed by foreign genes inserted in these vectors has been determined. Ad5 vectors replicate and express heterologous antigens in porcine lungs and mediastinal and mesenteric lymph nodes. Significant levels of heterologous antigen expression were also demonstrated in the small intestine (jejunum and ileum), but Ad5 replication in this organ was very poor, suggesting that Ad vectors undergo an abortive replication in the porcine small intestine. The tissues infected by Ad5 were dependent on the inoculation route. The oronasal route appeared to be best for inoculation of bronchus-associated lymphoid tissue infection, while the intraperitoneal route was best for gut-associated lymphoid tissue infection. Epithelial cells of bronchioles, macrophages, type II pneumocytes, and follicular dendritic cells were identified as targets for Ad5, while epithelial cells of the intestine were not infected by Ad5. Viruses with a deletion from 79.5 to 84.8 map units in the E3 region, with or without heterologous inserted genes, replicated to lower levels in porcine tissues than did wild-type Ad5. It was also shown that an Ad5 recombinant expressing the four antigenic sites (A, B, C, and D) of transmissible gastroenteritis coronavirus (TGEV) spike protein induced in swine immune responses which neutralized TGEV infectivity. In addition, porcine serum from Ad-TGEV-immune animals provide passive protection when mixed with fully virulent TGEV and orally administered to highly susceptible newborn piglets. These results taken together indicate that swine may be a good animal model for human Ad5 lung infection to aid in the evaluation of candidate adenovirus vaccines and that Ad5 may be suitable as a recombinant viral vaccine or for other applications in swine.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Andersson M, Päbo S, Nilsson T, Peterson PA. Impaired intracellular transport of class I MHC antigens as a possible means for adenoviruses to evade immune surveillance. Cell. 1985 Nov;43(1):215–222. [PubMed]
  • Berkner KL. Development of adenovirus vectors for the expression of heterologous genes. Biotechniques. 1988 Jul-Aug;6(7):616–629. [PubMed]
  • Berschneider HM, Powell DW. Fibroblasts modulate intestinal secretory responses to inflammatory mediators. J Clin Invest. 1992 Feb;89(2):484–489. [PMC free article] [PubMed]
  • Bett AJ, Krougliak V, Graham FL. DNA sequence of the deletion/insertion in early region 3 of Ad5 dl309. Virus Res. 1995 Nov;39(1):75–82. [PubMed]
  • Bett AJ, Prevec L, Graham FL. Packaging capacity and stability of human adenovirus type 5 vectors. J Virol. 1993 Oct;67(10):5911–5921. [PMC free article] [PubMed]
  • BETTS AO, JENNINGS AR, LAMONT PH, PAGE Z. Inoculation of pigs with adenoviruses of man. Nature. 1962 Jan 6;193:45–46. [PubMed]
  • Blair GE, Dixon SC, Griffiths SA, Zajdel ME. Restricted replication of human adenovirus type 5 in mouse cell lines. Virus Res. 1989 Dec;14(4):339–346. [PubMed]
  • Bohl EH, Gupta RK, Olquin MV, Saif LJ. Antibody responses in serum, colostrum, and milk of swine after infection or vaccination with transmissible gastroenteritis virus. Infect Immun. 1972 Sep;6(3):289–301. [PMC free article] [PubMed]
  • Branton PE, Evelegh M, Rowe DT, Graham FL, Bacchetti S. Protein kinase and ATP-binding activity associated with the 72-kdalton single-stranded DNA-binding protein from early region 2A of human adenovirus type 5. Can J Biochem Cell Biol. 1985 Sep;63(9):941–952. [PubMed]
  • Brasier AR, Tate JE, Habener JF. Optimized use of the firefly luciferase assay as a reporter gene in mammalian cell lines. Biotechniques. 1989 Nov-Dec;7(10):1116–1122. [PubMed]
  • Buchmeier MJ, Lewicki HA, Talbot PJ, Knobler RL. Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. Virology. 1984 Jan 30;132(2):261–270. [PubMed]
  • Burgert HG, Kvist S. An adenovirus type 2 glycoprotein blocks cell surface expression of human histocompatibility class I antigens. Cell. 1985 Jul;41(3):987–997. [PubMed]
  • Correa I, Jiménez G, Suñ C, Bullido MJ, Enjuanes L. Antigenic structure of the E2 glycoprotein from transmissible gastroenteritis coronavirus. Virus Res. 1988 Apr;10(1):77–93. [PubMed]
  • De Diego M, Laviada MD, Enjuanes L, Escribano JM. Epitope specificity of protective lactogenic immunity against swine transmissible gastroenteritis virus. J Virol. 1992 Nov;66(11):6502–6508. [PMC free article] [PubMed]
  • De Diego M, Rodríguez F, Alcaraz C, Gómez N, Alonso C, Escribano JM. Characterization of the IgA and subclass IgG responses to neutralizing epitopes after infection of pregnant sows with the transmissible gastroenteritis virus or the antigenically related porcine respiratory coronavirus. J Gen Virol. 1994 Oct;75(Pt 10):2585–2593. [PubMed]
  • Delmas B, Gelfi J, Laude H. Antigenic structure of transmissible gastroenteritis virus. II. Domains in the peplomer glycoprotein. J Gen Virol. 1986 Jul;67(Pt 7):1405–1418. [PubMed]
  • Delmas B, Rasschaert D, Godet M, Gelfi J, Laude H. Four major antigenic sites of the coronavirus transmissible gastroenteritis virus are located on the amino-terminal half of spike glycoprotein S. J Gen Virol. 1990 Jun;71(Pt 6):1313–1323. [PubMed]
  • Gebauer F, Posthumus WP, Correa I, Suñ C, Smerdou C, Sánchez CM, Lenstra JA, Meloen RH, Enjuanes L. Residues involved in the antigenic sites of transmissible gastroenteritis coronavirus S glycoprotein. Virology. 1991 Jul;183(1):225–238. [PubMed]
  • GINSBERG HS, HORSFALL FL., Jr Quantitative aspects of the multiplication of influenza A virus in the mouse lung; relation between the degree of viral multiplication and the extent of pneumonia. J Exp Med. 1952 Feb;95(2):135–145. [PMC free article] [PubMed]
  • Ginsberg HS, Lundholm-Beauchamp U, Horswood RL, Pernis B, Wold WS, Chanock RM, Prince GA. Role of early region 3 (E3) in pathogenesis of adenovirus disease. Proc Natl Acad Sci U S A. 1989 May;86(10):3823–3827. [PMC free article] [PubMed]
  • Godet M, Grosclaude J, Delmas B, Laude H. Major receptor-binding and neutralization determinants are located within the same domain of the transmissible gastroenteritis virus (coronavirus) spike protein. J Virol. 1994 Dec;68(12):8008–8016. [PMC free article] [PubMed]
  • Gooding LR, Wold WS. Molecular mechanisms by which adenoviruses counteract antiviral immune defenses. Crit Rev Immunol. 1990;10(1):53–71. [PubMed]
  • Graham FL, Prevec L. Adenovirus-based expression vectors and recombinant vaccines. Biotechnology. 1992;20:363–390. [PubMed]
  • Graham FL, Smiley J, Russell WC, Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. [PubMed]
  • Hjorth RN, Bonde GM, Pierzchala WA, Vernon SK, Wiener FP, Levner MH, Lubeck MD, Hung PP. A new hamster model for adenoviral vaccination. Arch Virol. 1988;100(3-4):279–283. [PubMed]
  • HORSFALL FL, Jr, GINSBERG HS. The dependence of the pathological lesion upon the multiplication of pneumonia virus of mice (PVM); kinetic relation between the degree of viral multiplication and the extent of pneumonia. J Exp Med. 1951 Feb;93(2):139–150. [PMC free article] [PubMed]
  • Jackson S, Sogn JA, Kindt TJ. Microdetermination of rabbit immunoglobulin allotypes by ELISA using specific antibodies conjugated with peroxidase or with biotin. J Immunol Methods. 1982;48(3):299–309. [PubMed]
  • Jiménez G, Correa I, Melgosa MP, Bullido MJ, Enjuanes L. Critical epitopes in transmissible gastroenteritis virus neutralization. J Virol. 1986 Oct;60(1):131–139. [PMC free article] [PubMed]
  • Jones N, Shenk T. Isolation of adenovirus type 5 host range deletion mutants defective for transformation of rat embryo cells. Cell. 1979 Jul;17(3):683–689. [PubMed]
  • Jüttermann R, Weyer U, Doerfler W. Defect of adenovirus type 12 replication in hamster cells: absence of transcription of viral virus-associated and L1 RNAs. J Virol. 1989 Aug;63(8):3535–3540. [PMC free article] [PubMed]
  • Laude H, Gelfi J, Lavenant L, Charley B. Single amino acid changes in the viral glycoprotein M affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus. J Virol. 1992 Feb;66(2):743–749. [PMC free article] [PubMed]
  • Liu YJ, Joshua DE, Williams GT, Smith CA, Gordon J, MacLennan IC. Mechanism of antigen-driven selection in germinal centres. Nature. 1989 Dec 21;342(6252):929–931. [PubMed]
  • Lubeck MD, Natuk RJ, Chengalvala M, Chanda PK, Murthy KK, Murthy S, Mizutani S, Lee SG, Wade MS, Bhat BM, et al. Immunogenicity of recombinant adenovirus-human immunodeficiency virus vaccines in chimpanzees following intranasal administration. AIDS Res Hum Retroviruses. 1994 Nov;10(11):1443–1449. [PubMed]
  • Meiklejohn G. Viral respiratory disease at Lowry Air Force Base in Denver, 1952-1982. J Infect Dis. 1983 Nov;148(5):775–784. [PubMed]
  • Mittal SK, McDermott MR, Johnson DC, Prevec L, Graham FL. Monitoring foreign gene expression by a human adenovirus-based vector using the firefly luciferase gene as a reporter. Virus Res. 1993 Apr;28(1):67–90. [PubMed]
  • Natuk RJ, Lubeck MD, Chanda PK, Chengalvala M, Wade MS, Murthy SC, Wilhelm J, Vernon SK, Dheer SK, Mizutani S, et al. Immunogenicity of recombinant human adenovirus-human immunodeficiency virus vaccines in chimpanzees. AIDS Res Hum Retroviruses. 1993 May;9(5):395–404. [PubMed]
  • Nevins JR. Regulation of early adenovirus gene expression. Microbiol Rev. 1987 Dec;51(4):419–430. [PMC free article] [PubMed]
  • Prevec L, Schneider M, Rosenthal KL, Belbeck LW, Derbyshire JB, Graham FL. Use of human adenovirus-based vectors for antigen expression in animals. J Gen Virol. 1989 Feb;70(Pt 2):429–434. [PubMed]
  • Prince GA, Porter DD, Jenson AB, Horswood RL, Chanock RM, Ginsberg HS. Pathogenesis of adenovirus type 5 pneumonia in cotton rats (Sigmodon hispidus). J Virol. 1993 Jan;67(1):101–111. [PMC free article] [PubMed]
  • Saif LJ, Bohl EH, Gupta RK. Isolation of porcine immunoglobulins and determination of the immunoglobulin classes of transmissible gastroenteritis viral antibodies. Infect Immun. 1972 Oct;6(4):600–609. [PMC free article] [PubMed]
  • Sánchez CM, Jiménez G, Laviada MD, Correa I, Suñ C, Bullido M j, Gebauer F, Smerdou C, Callebaut P, Escribano JM, et al. Antigenic homology among coronaviruses related to transmissible gastroenteritis virus. Virology. 1990 Feb;174(2):410–417. [PubMed]
  • Silverstein G, Strohl WA. Restricted replication of adenovirus type 2 in mouse Balb/3T3 cells. Arch Virol. 1986;87(3-4):241–264. [PubMed]
  • Suñ C, Jiménez G, Correa I, Bullido MJ, Gebauer F, Smerdou C, Enjuanes L. Mechanisms of transmissible gastroenteritis coronavirus neutralization. Virology. 1990 Aug;177(2):559–569. [PubMed]
  • Takafuji ET, Gaydos JC, Allen RG, Top FH., Jr Simultaneous administration of live, enteric-coated adenovirus types 4, 7 and 21 vaccines: safety and immunogenicity. J Infect Dis. 1979 Jul;140(1):48–53. [PubMed]
  • Tew JG, Kosco MH, Burton GF, Szakal AK. Follicular dendritic cells as accessory cells. Immunol Rev. 1990 Oct;117:185–211. [PubMed]
  • Torres JM, Sánchez C, Suñ C, Smerdou C, Prevec L, Graham F, Enjuanes L. Induction of antibodies protecting against transmissible gastroenteritis coronavirus (TGEV) by recombinant adenovirus expressing TGEV spike protein. Virology. 1995 Nov 10;213(2):503–516. [PubMed]
  • VanCott JL, Brim TA, Lunney JK, Saif LJ. Contribution of antibody-secreting cells induced in mucosal lymphoid tissues of pigs inoculated with respiratory or enteric strains of coronavirus to immunity against enteric coronavirus challenge. J Immunol. 1994 Apr 15;152(8):3980–3990. [PubMed]
  • VanCott JL, Brim TA, Simkins RA, Saif LJ. Isotype-specific antibody-secreting cells to transmissible gastroenteritis virus and porcine respiratory coronavirus in gut- and bronchus-associated lymphoid tissues of suckling pigs. J Immunol. 1993 May 1;150(9):3990–4000. [PubMed]
  • Wold WS, Gooding LR. Region E3 of adenovirus: a cassette of genes involved in host immunosurveillance and virus-cell interactions. Virology. 1991 Sep;184(1):1–8. [PubMed]

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