J Vet Sci.  2012 Mar;13(1):59-65. 10.4142/jvs.2012.13.1.59.

Induction of humoral responses to BHV-1 glycoprotein D expressed by HSV-1 amplicon vectors

• Blanc AM
• Berois MB
• Tome LM
• Epstein AL
• Arbiza JR

• KMID: 1365004
• DOI: http://doi.org/10.4142/jvs.2012.13.1.59

Abstract

Herpes simplex virus type-1 (HSV-1) amplicon vectors are versatile and useful tools for transferring genes into cells that are capable of stimulating a specific immune response to their expressed antigens. In this work, two HSV-1-derived amplicon vectors were generated. One of these expressed the full-length glycoprotein D (gD) of bovine herpesvirus 1 while the second expressed the truncated form of gD (gDtr) which lacked the trans-membrane region. After evaluating gD expression in the infected cells, the ability of both vectors to induce a specific gD immune response was tested in BALB/c mice that were intramuscularly immunized. Specific serum antibody responses were detected in mice inoculated with both vectors, and the response against truncated gD was higher than the response against full-length gD. These results reinforce previous findings that HSV-1 amplicon vectors can potentially deliver antigens to animals and highlight the prospective use of these vectors for treating infectious bovine rhinotracheitis disease.

Keyword

antibody response; BHV-1 gD; HSV-1 amplicon vectors; immunization

MeSH Terms

Animals
Antibodies, Viral/blood
Blotting, Western/veterinary
Cattle
Female
Genetic Vectors/*immunology
Herpesvirus 1, Bovine/genetics/*immunology
Herpesvirus 1, Human/genetics/*immunology
Immunity, Humoral/immunology
Immunization/methods/veterinary
Infectious Bovine Rhinotracheitis/*immunology/prevention & control/virology
Mice
Mice, Inbred BALB C
Neutralization Tests/veterinary
Specific Pathogen-Free Organisms
Viral Proteins/genetics/*immunology
Viral Vaccines/immunology

Figure

• 

  Fig. 1 Amplicon plasmids constructs. (A) Amplicon plasmid pAEUA2 contained sequences required for amplicon replication (Ori-S) and packaging (a). The multiple cloning site (MCS) located between the human cytomegalovirus promoter (HCMV) and a polyadenylation signal of simian virus 40 (pASV40) contained unique NotI, XbaI, and NheI restriction sites. The enhanced green fluorescent protein (EGFP) reporter gene was placed between the herpes simplex virus type 1 (HSV-1) immediate-early promoter (PIE4/5) and bovine growth hormone polyadenylation signal (pABGH). Amp R: ampicillin resistance, colE1: plasmid origin of replication. (B) Schematic diagram of glycoprotein D (gD) of bovine herpesvirus 1 showing the signal peptide, ectodomain, and transmembrane region. (C) Schematic diagram of truncated form of gD.

• 

  Fig. 2 Glycoprotein D (gD) and truncated form of gD (gDtr) expression in Gli36 cells. The upper panels show Gli36 cells transfected with pAgD BHV-1 (A), pAgDtr BHV-1 (B), and pAEUA2 (C). The lower panels show Gli36 cells infected with vAgD BHV-1 (D), vAgDtr BHV-1 (E), and vAEUA2 (F). gD glycoprotein was detected by immunofluorescence using the monoclonal antibody 1106 and secondary antibody anti-mouse IgG H+L Alexa Fluor 555 (red). EGFP expression was observed and appeared green. Scale bar = 50 µm.

• 

  Fig. 3 Antibody response against BHV-1 gD in immunized BALB/c mice. Six 8-week old mice were vaccinated twice at 21-day intervals with vAEUA2, vAgD BHV-1, and vAgDtr BHV-1. Groups of three mice were injected intramuscularly with 5 × 105 TU/mL of amplicon vector. In panel A, the bars represent the antibody titers for mice treated with (a) the control amplicon vector vAEUA2 expressing no gD, (b) amplicon vector vAgD BHV-1 expressing full-length gD, and (c) amplicon vector vAgDtr BHV-1 expressing gDtr. Data represent the mean ± SD for two independent experiments. *p < 0.05 and **p < 0.01 (determined by Student's t-test relative to the control). In panel B, the reactivity of mice sera was tested by Western blotting. Serum pool (day 36 p.i.) of mice immunized with vAgDtr BHV-1 (Lane a), vAgD BHV-1 (Lane b), or vAEUA2 (Lane c) were evaluated. A pool of pre-immune mouse serum (Lane d) was used as a negative control. Positions of molecular weight markers are indicated on the left of the image.

Reference

1. Cuchet D, Ferrera R, Lomonte P, Epstein AL. Characterization of antiproliferative and cytotoxic properties of the HSV-1 immediate-early ICPo protein. J Gene Med. 2005. 7:1187–1199.

2. D'Antuono A, Laimbacher AS, La Torre J, Tribulatti V, Romanutti C, Zamorano P, Quattrocchi V, Schraner EM, Ackermann M, Fraefel C, Mattion N. HSV-1 amplicon vectors that direct the in situ production of foot-and-mouth disease virus antigens in mammalian cells can be used for genetic immunization. Vaccine. 2010. 28:7363–7372.

3. Dasika GK, Letchworth GJ. Homologous and heterologous interference requires bovine herpesvirus-1 glycoprotein D at the cell surface during virus entry. J Gen Virol. 2000. 81:1041–1049.

4. Donofrio G, Sartori C, Franceschi V, Capocefalo A, Cavirani S, Taddei S, Flammini CF. Double immunization strategy with a BoHV-4-vectorialized secreted chimeric peptide BVDV-E2/BoHV-1-gD. Vaccine. 2008. 26:6031–6042.

5. Dubuisson J, Israel BA, Letchworth GJ 3rd. Mechanisms of bovine herpesvirus type 1 neutralization by monoclonal antibodies to glycoproteins gI, gIII and gIV. J Gen Virol. 1992. 73:2031–2039.

6. Epstein AL. HSV-1-derived amplicon vectors: recent technological improvements and remaining difficulties--a review. Mem Inst Oswaldo Cruz. 2009. 104:399–410.

7. Epstein AL. HSV-1-derived recombinant and amplicon vectors for preventive or therapeutic gene transfer: an overview. Gene Ther. 2005. 12:Suppl 1. S153.

8. Hocknell PK, Wiley RD, Wang X, Evans TG, Bowers WJ, Hanke T, Federoff HJ, Dewhurst S. Expression of human immunodeficiency virus type 1 gp120 from herpes simplex virus type 1-derived amplicons results in potent, specific, and durable cellular and humoral immune responses. J Virol. 2002. 76:5565–5580.

9. Hughes G, Babiuk LA, van Drunen Littel-van den Hurk S. Functional and topographical analyses of epitopes on bovine herpesvirus type 1 glycoprotein IV. Arch Virol. 1988. 103:47–60.

10. Kashima T, Vinters HV, Campagnoni AT. Unexpected expression of intermediate filament protein genes in human oligodendroglioma cell lines. J Neuropathol Exp Neurol. 1995. 54:23–31.

11. Khattar SK, Collins PL, Samal SK. Immunization of cattle with recombinant Newcastle disease virus expressing bovine herpesvirus-1 (BHV-1) glycoprotein D induces mucosal and serum antibody responses and provides partial protection against BHV-1. Vaccine. 2010. 28:3159–3170.

12. Krisky DM, Marconi PC, Oligino T, Rouse RJ, Fink DJ, Glorioso JC. Rapid method for construction of recombinant HSV gene transfer vectors. Gene Ther. 1997. 4:1120–1125.

13. Lemaire M, Schynts F, Meyer G, Thiry E. Antibody response to glycoprotein E after bovine herpesvirus type 1 infection in passively immunised, glycoprotein E-negative calves. Vet Rec. 1999. 144:172–176.

14. Lewis PJ, Cox GJ, van Drunen Littel-van den Hurk S, Babiuk LA. Polynucleotide vaccines in animals: enhancing and modulating responses. Vaccine. 1997. 15:861–864.

15. Lewis PJ, van Drunen Littel-van den H, Babiuk LA. Altering the cellular location of an antigen expressed by a DNA-based vaccine modulates the immune response. J Virol. 1999. 73:10214–10223.

16. Lewis PJ, van Drunen Littel-Van Den H, Babiuk LA. Induction of immune responses to bovine herpesvirus type 1 gD in passively immune mice after immunization with a DNA-based vaccine. J Gen Virol. 1999. 80:2829–2837.

17. Marshall RL, Israel BA, Letchworth GJ 3rd. Monoclonal antibody analysis of bovine herpesvirus-1 glycoprotein antigenic areas relevant to natural infection. Virology. 1988. 165:338–347.

18. Mittal SK, Papp Z, Tikoo SK, Baca-Estrada ME, Yoo D, Benko M, Babiuk LA. Induction of systemic and mucosal immune responses in cotton rats immunized with human adenovirus type 5 recombinants expressing the full and truncated forms of bovine herpesvirus type 1 glycoprotein gD. Virology. 1996. 222:299–309.

19. Monaco JJ. A molecular model of MHC class-I-restricted antigen processing. Immunol Today. 1992. 13:173–179.

20. Peralta A, Molinari P, Conte-Grand D, Calamante G, Taboga O. A chimeric baculovirus displaying bovine herpesvirus-1 (BHV-1) glycoprotein D on its surface and their immunological properties. Appl Microbiol Biotechnol. 2007. 75:407–414.

21. Tikoo SK, Campos M, Babiuk LA. Bovine herpesvirus 1 (BHV-1): biology, pathogenesis, and control. Adv Virus Res. 1995. 45:191–223.

22. Tikoo SK, Fitzpatrick DR, Babiuk LA, Zamb TJ. Molecular cloning, sequencing, and expression of functional bovine herpesvirus 1 glycoprotein gIV in transfected bovine cells. J Virol. 1990. 64:5132–5142.

23. Toussaint JF, Coen L, Letellier C, Dispas M, Gillet L, Vanderplasschen A, Kerkhofs P. Genetic immunization of cattle against bovine herpesvirus 1: glycoprotein gD confers higher protection than glycoprotein gC or tegument protein VP8. Vet Res. 2005. 36:529–544.

24. van Drunen Littel-van den Hurk , Braun RP, Lewis PJ, Karvonen BC, Baca-Estrada ME, Snider M, McCartney D, Watts T, Babiuk LA. Intradermal immunization with a bovine herpesvirus-1 DNA vaccine induces protective immunity in cattle. J Gen Virol. 1998. 79:831–839.

25. van Drunen Littel-van den Hurk S, Babiuk LA. Synthesis and processing of bovine herpesvirus 1 glycoproteins. J Virol. 1986. 59:401–410.

26. van Drunen Littel-van den Hurk S, Tikoo SK, Liang X, Babiuk LA. Bovine herpesvirus-1 vaccines. Immunol Cell Biol. 1993. 71:405–420.

27. Yates WD. A review of infectious bovine rhinotracheitis, shipping fever pneumonia and viral-bacterial synergism in respiratory disease of cattle. Can J Comp Med. 1982. 46:225–263.

28. Zakhartchouk AN, Reddy PS, Baxi M, Baca-Estrada ME, Mehtali M, Babiuk LA, Tikoo SK. Construction and characterization of E3-deleted bovine adenovirus type 3 expressing full-length and truncated form of bovine herpesvirus type 1 glycoprotein gD. Virology. 1998. 250:220–229.

29. Zaupa C, Revol-Guyot V, Epstein A. Improved packaging system for generation of high-level noncytotoxic HSV-1 amplicon vectors using Cre-loxP site-specific recombination to delete the packaging signals of defective helper genomes. Human Gene Therapy. 2003. 14:1049–1063.