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The Murine Intravaginal HSV-2 Challenge Model for Investigation of DNA Vaccines

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Herpes Simplex Virus

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1144))

Abstract

DNA vaccines have been licensed in veterinary medicine and have promise for humans. This format is relatively immunogenic in mice and guinea pigs, the two principle HSV-2 animal models, permitting rapid assessment of vectors, antigens, adjuvants, and delivery systems. Limitations include the relatively poor immunogenicity of naked DNA in humans and the profound differences in HSV-2 pathogenesis between host species. Herein, we detail lessons learned over the last few years investigating candidate DNA vaccines in the progesterone-primed female mouse vaginal model of HSV-2 infection as a guide to investigators in the field.

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References

  1. Tronstein E, Johnston C, Huang ML, Selke S, Magaret A, Warren T, Corey L, Wald A (2011) Genital shedding of herpes simplex virus among symptomatic and asymptomatic persons with HSV-2 infection. JAMA 305:1441–1449

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Kask AS, Chen X, Marshak JO, Dong L, Saracino M, Chen D, Jarrahian C, Kendall MA, Koelle DM (2010) DNA vaccine delivery by densely-packed and short microprojection arrays to skin protects against vaginal HSV-2 challenge. Vaccine 28:7483–7491

    Article  PubMed  CAS  Google Scholar 

  3. Feldman LT, Ellison AR, Voytek CC, Yang L, Krause P, Margolis TP (2002) Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice. Proc Natl Acad Sci U S A 99:978–983

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Freeman ML, Sheridan BS, Bonneau RH, Hendricks RL (2007) Psychological stress compromises CD8+ T cell control of latent herpes simplex virus type 1 infections. J Immunol 179:322–328

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Johnston C, Koelle DM, Wald A (2011) HSV-2: in pursuit of a vaccine. J Clin Invest 121:4600–4609

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Parr MB, Kepple L, McDermott MR, Drew MD, Bozzola JJ, Parr EL (1994) A mouse model for studies of mucosal immunity to vaginal infection by herpes simplex virus type 2. Lab Invest 70:369–380

    PubMed  CAS  Google Scholar 

  7. Linehan MM, Richman S, Krummenacher C, Eisenberg RJ, Cohen GH, Iwasaki A (2004) In vivo role of nectin-1 in entry of herpes simplex virus type 1 (HSV-1) and HSV-2 through the vaginal mucosa. J Virol 78:2530–2536

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Cherpes TL, Busch JL, Sheridan BS, Harvey SA, Hendricks RL (2008) Medroxyprogesterone acetate inhibits CD8+ T cell viral-specific effector function and induces herpes simplex virus type 1 reactivation. J Immunol 181:969–975

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Lopez C (1975) Genetics of natural resistance to herpes virus infections in mice. Nature 258:1352–1353

    Article  Google Scholar 

  10. St Leger AJ, Peters B, Sidney J, Sette A, Hendricks RL (2011) Defining the herpes simplex virus-specific CD8+ T cell repertoire in C57BL/6 mice. J Immunol 186:3927–3933

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. Gebhardt T, Whitney PG, Zaid A, Mackay LK, Brooks AG, Heath WR, Carbone FR, Mueller SN (2011) Different patterns of peripheral migration by memory CD4+ and CD8+ T cells. Nature 477:216–219

    Article  PubMed  CAS  Google Scholar 

  12. Muller WJ, Dong L, Vilalta A, Byrd B, Wilhelm KM, McClurkan CL, Margalith M, Liu C, Kaslow D, Sidney J, Sette A, Koelle DM (2009) Herpes simplex virus type 2 tegument proteins contain subdominant T-cell epitopes detectable in BALB/c mice after DNA immunization and infection. J Gen Virol 90:1153–1163

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  13. Shlapobersky M, Marshak JO, Dong L, Huang ML, Wei Q, Chu A, Rolland A, Sullivan S, Koelle DM (2012) Vaxfectin-adjuvanted plasmid DNA vaccine improves protection and immunogenicity in a murine model of genital herpes infection. J Gen Virol 93:1305–1315

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Sin JI, Kim JJ, Zhang D, Weiner DB (2001) Modulation of cellular responses by plasmid CD40L: CD40L plasmid vectors enhance antigen-specific helper T cell type 1 CD4+ T cell-mediated protective immunity against herpes simplex virus type 2 in vivo. Hum Gene Ther 12:1091–1102

    Article  PubMed  CAS  Google Scholar 

  15. Chen X, Kask AS, Crichton ML, McNeilly C, Yukiko S, Dong L, Marshak JO, Jarrahian C, Fernando GJ, Chen D, Koelle DM, Kendall MA (2010) Improved DNA vaccination by skin-targeted delivery using dry-coated densely-packed microprojection arrays. J Control Release 148(3):327–333

    Article  PubMed  CAS  Google Scholar 

  16. Glenting J, Wessels S (2005) Ensuring safety of DNA vaccines. Microb Cell Fact 4:26

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Dutton J, Li B, Woo W-P, Marshak K, Xu Y, Huang ML, Dong L, Frazer I, Koelle D (2012) Protection against viral challenge in a murine model of HSV-2 infection conferred by mixed DNA vaccines. Presented at 37th International Herpesvirus Workshop, Calgary, Alberta, Canada

    Google Scholar 

  18. Liu W, Gao F, Zhao KN, Zhao W, Fernando GJ, Thomas R, Frazer IH (2002) Codon modified human papillomavirus type 16 E7 DNA vaccine enhances cytotoxic T-lymphocyte induction and anti-tumour activity. Virology 301:43–52

    Article  PubMed  CAS  Google Scholar 

  19. Everett RD, Fenwick ML (1990) Comparative DNA sequence analysis of the host shutoff genes of different strains of herpes simplex virus: type 2 strain HG52 encodes a truncated UL41 product. J Gen Virol 71(Pt 6):1387–1390

    Article  PubMed  CAS  Google Scholar 

  20. Dudek TE, Torres-Lopez E, Crumpacker C, Knipe DM (2011) Evidence for differences in immunologic and pathogenesis properties of herpes simplex virus 2 strains from the United States and South Africa. J Infect Dis 203:1434–1441

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Stanberry LR, Kit S, Myers MG (1985) Thymidine kinase-deficient herpes simplex virus type 2 genital infection in guinea pigs. J Virol 55:322–328

    PubMed Central  PubMed  CAS  Google Scholar 

  22. Nakanishi Y, Lu B, Gerard C, Iwasaki A (2009) CD8(+) T lymphocyte mobilization to virus-infected tissue requires CD4(+) T-cell help. Nature 462:510–513

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Halford WP, Puschel R, Gershburg E, Wilber A, Gershburg S, Rakowski B (2011) A live-attenuated HSV-2 ICP0 virus elicits 10 to 100 times greater protection against genital herpes than a glycoprotein D subunit vaccine. PLoS One 6:e17748

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Magaret AS, Wald A, Huang ML, Selke S, Corey L (2007) Optimizing PCR positivity criterion for detection of herpes simplex virus DNA on skin and mucosa. J Clin Microbiol 45:1618–1620

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. McClements WL, Armstrong ME, Keys RD, Liu MA (1996) Immunization with DNA vaccines encoding glycoprotein D or glycoprotein B, alone or in combination, induces protective immunity in animal models of herpes simplex virus-2 disease. Proc Natl Acad Sci U S A 93:11414–11420

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Belshe RB, Leone PA, Bernstein DI, Wald A, Levin MJ, Stapleton JT, Gorfinkel I, Morrow RL, Ewell MG, Stokes-Riner A, Dubin G, Heineman TC, Schulte JM, Deal CD (2012) Efficacy results of a trial of a herpes simplex vaccine. N Engl J Med 366:34–43

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Cattamanchi A, Posavad CM, Wald A, Baine Y, Moses J, Higgins TJ, Ginsberg R, Ciccarelli R, Corey L, Koelle DM (2008) Phase I study of a herpes simplex virus type 2 (HSV-2) DNA vaccine administered to healthy, HSV-2-seronegative adults by a needle-free injection system. Clin Vaccine Immunol 15:1638–1643

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Marshak JO, Kask A, Dong L, Koelle MD (2014) University of Washington

    Google Scholar 

  29. Lekstrom-Himes JA, Pesnicak L, Straus SE (1998) The quantity of latent viral DNA correlates with the relative rates at which herpes simplex virus types 1 and 2 cause recurrent genital herpes outbreaks. J Virol 72:2760–2764

    PubMed Central  PubMed  CAS  Google Scholar 

  30. Khanna KM, Bonneau RH, Kinchington PR, Hendricks RL (2003) Herpes simplex virus-specific memory CD8(+) T cells are selectively activated and retained in latently infected sensory ganglia. Immunity 18:593–603

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  31. Herbst-Kralovetz MM, Pyles RB (2006) Quantification of poly(I:C)-mediated protection against genital herpes simplex virus type 2 infection. J Virol 80:9988–9997

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  32. Strasser JE, Arnold RL, Pachuk C, Higgins TJ, Bernstein DI (2000) Herpes simplex virus DNA vaccine efficacy: effect of glycoprotein D plasmid constructs. J Infect Dis 182:1304–1310

    Article  PubMed  CAS  Google Scholar 

  33. Koelle DM (2003) Expression cloning for the discovery of viral antigens and epitopes recognized by T-cells. Methods 29:213–226

    Article  PubMed  CAS  Google Scholar 

  34. Laing KJ, Dong L, Sidney J, Sette A, Koelle DM (2012) Immunology in the clinic review series; focus on host responses: T cell responses to herpes simplex viruses. Clin Exp Immunol 167:47–58

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  35. Malin SA, Davis BM, Molliver DC (2007) Production of dissociated sensory neuron cultures and considerations for their use in studying neuronal function and plasticity. Nat Protoc 2:152–160

    Article  PubMed  CAS  Google Scholar 

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Correspondence to David M. Koelle M.D. .

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Marshak, J.O., Dong, L., Koelle, D.M. (2014). The Murine Intravaginal HSV-2 Challenge Model for Investigation of DNA Vaccines. In: Diefenbach, R., Fraefel, C. (eds) Herpes Simplex Virus. Methods in Molecular Biology, vol 1144. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0428-0_21

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  • DOI: https://doi.org/10.1007/978-1-4939-0428-0_21

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0427-3

  • Online ISBN: 978-1-4939-0428-0

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