1887

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Volume 93, Issue 6

Vaxfectin-adjuvanted plasmid DNA vaccine improves protection and immunogenicity in a murine model of genital herpes infection Free

Abstract

The herpes simplex type 2 (HSV-2) envelope glycoprotein (gD2) was evaluated as a potential antigen candidate for a plasmid DNA (pDNA)-based HSV-2 vaccine. The pDNA was formulated with Vaxfectin, a cationic lipid-based adjuvant, and tested in a murine HSV-2 lethal challenge model. gD2 was expressed as full-length (FL) and secreted (S) gD2 forms. A 0.1 µg pDNA dose was tested to distinguish treatment conditions for survival and a 100 µg pDNA dose was tested to distinguish treatment conditions for reduction in vaginal and latent HSV-2 copies. Vaxfectin-formulated gD2 pDNA significantly increased serum IgG titres and survival for both FL gD2 and S gD2 compared with gD2 pDNA alone. Mice immunized with FL gD2 formulated with Vaxfectin showed reduction in vaginal and dorsal root ganglia (DRG) HSV-2 copies. The stringency of this protection was further evaluated by testing Vaxfectin-formulated FL gD2 pDNA at a high 500 LD inoculum. At this high viral challenge, the 0.1 µg dose of FL gD2 Vaxfectin-formulated pDNA yielded 80 % survival compared with no survival for FL gD2 pDNA alone. Vaxfectin-formulated FL gD2 pDNA, administered at a 100 µg pDNA dose, significantly reduced HSV-2 DNA copy number, compared with FL gD2 DNA alone. In addition, 40 % of mice vaccinated with adjuvanted FL pDNA had no detectable HSV-2 viral genomes in the DRG, whereas all mice vaccinated with gD2 pDNA alone were positive for HSV-2 viral genomes. These results show the potential contribution of Vaxfectin-gD2 pDNA to a future multivalent HSV-2 vaccine.

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  • Accepted:
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© 2012 Vical Incorporated
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2012-06-01
2024-04-19
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References

  1. Aumakhan B., Hardick A., Quinn T. C., Laeyendecker O., Gange S. J., Beyrer C., Cox C., Anastos K., Cohen M. other authors 2010; Genital herpes evaluation by quantitative TaqMan PCR: correlating single detection and quantity of HSV-2 DNA in cervicovaginal lavage fluids with cross-sectional and longitudinal clinical data. Virol J 7:328 [View Article][PubMed]
     [Google Scholar]
  2. Balachandran N., Bacchetti S., Rawls W. E. 1982; Protection against lethal challenge of BALB/c mice by passive transfer of monoclonal antibodies to five glycoproteins of herpes simplex virus type 2. Infect Immun 37:1132–1137[PubMed]
     [Google Scholar]
  3. Belshe R. B., Leone P. A., Bernstein D. I., Wald A., Levin M. J., Stapleton J. T., Gorfinkel I., Morrow R. L., Ewell M. G. other authors 2012; Efficacy results of a trial of a herpes simplex vaccine. N Engl J Med 366:34–43 [View Article][PubMed]
     [Google Scholar]
  4. BenMohamed L., Bertrand G., McNamara C. D., Gras-Masse H., Hammer J., Wechsler S. L., Nesburn A. B. 2003; Identification of novel immunodominant CD4+ Th1-type T-cell peptide epitopes from herpes simplex virus glycoprotein D that confer protective immunity. J Virol 77:9463–9473 [View Article][PubMed]
     [Google Scholar]
  5. Bernstein D. I., Aoki F. Y., Tyring S. K., Stanberry L. R., St-Pierre C., Shafran S. D., Leroux-Roels G., Van Herck K., Bollaerts A., Dubin G. Glaxo Smith Kline Herpes Vaccine Study Group 2005; Safety and immunogenicity of glycoprotein D-adjuvant genital herpes vaccine. Clin Infect Dis 40:1271–1281 [View Article][PubMed]
     [Google Scholar]
  6. Bourne N., Milligan G. N., Schleiss M. R., Bernstein D. I., Stanberry L. R. 1996; DNA immunization confers protective immunity on mice challenged intravaginally with herpes simplex virus type 2. Vaccine 14:1230–1234 [View Article][PubMed]
     [Google Scholar]
  7. Bourne N., Pyles R. B., Bernstein D. I., Stanberry L. R. 2002; Modification of primary and recurrent genital herpes in guinea pigs by passive immunization. J Gen Virol 83:2797–2801[PubMed]
     [Google Scholar]
  8. Bourne N., Milligan G. N., Stanberry L. R., Stegall R., Pyles R. B. 2005; Impact of immunization with glycoprotein D2/AS04 on herpes simplex virus type 2 shedding into the genital tract in guinea pigs that become infected. J Infect Dis 192:2117–2123 [View Article][PubMed]
     [Google Scholar]
  9. Cattamanchi A., Posavad C. M., Wald A., Baine Y., Moses J., Higgins T. J., Ginsberg R., Ciccarelli R., Corey L., Koelle D. M. 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 [View Article][PubMed]
     [Google Scholar]
  10. Chen C. Y., Ballard R. C., Beck-Sague C. M., Dangor Y., Radebe F., Schmid S., Weiss J. B., Tshabalala V., Fehler G. other authors 2000; Human immunodeficiency virus infection and genital ulcer disease in South Africa: the herpetic connection. Sex Transm Dis 27:21–29 [View Article][PubMed]
     [Google Scholar]
  11. Chentoufi A. A., Zhang X., Lamberth K., Dasgupta G., Bettahi I., Nguyen A., Wu M., Zhu X., Mohebbi A. other authors 2008; HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D. J Immunol 180:426–437[PubMed] [CrossRef]
     [Google Scholar]
  12. Coen D. M., Kosz-Vnenchak M., Jacobson J. G., Leib D. A., Bogard C. L., Schaffer P. A., Tyler K. L., Knipe D. M. 1989; Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate. Proc Natl Acad Sci U S A 86:4736–4740 [View Article][PubMed]
     [Google Scholar]
  13. Cohen J. 2010; Immunology. Painful failure of promising genital herpes vaccine. Science 330:304 [View Article][PubMed]
     [Google Scholar]
  14. Corey L., Langenberg A. G., Ashley R., Sekulovich R. E., Izu A. E., Douglas J. M. Jr, Handsfield H. H., Warren T., Marr L. other authors 1999; Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials. JAMA 282:331–340 [View Article][PubMed]
     [Google Scholar]
  15. Corey L., Wald A., Celum C. L., Quinn T. C. 2004; The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics. J Acquir Immune Defic Syndr 35:435–445 [View Article][PubMed]
     [Google Scholar]
  16. Dolan A., Jamieson F. E., Cunningham C., Barnett B. C., McGeoch D. J. 1998; The genome sequence of herpes simplex virus type 2. J Virol 72:2010–2021[PubMed]
     [Google Scholar]
  17. Donnelly J. J., Ulmer J. B., Liu M. A. 1997; DNA vaccines. Life Sci 60:163–172 [View Article][PubMed]
     [Google Scholar]
  18. Fló J. 2003; Co-immunization with plasmids coding the full length and a soluble form of glycoprotein D of HSV-2 induces protective cellular and humoral immune response in mice. Vaccine 21:1239–1245 [View Article][PubMed]
     [Google Scholar]
  19. Hartikka J., Sawdey M., Cornefert-Jensen F., Margalith M., Barnhart K., Nolasco M., Vahlsing H. L., Meek J., Marquet M. other authors 1996; An improved plasmid DNA expression vector for direct injection into skeletal muscle. Hum Gene Ther 7:1205–1217 [View Article][PubMed]
     [Google Scholar]
  20. Hartikka J., Bozoukova V., Ferrari M., Sukhu L., Enas J., Sawdey M., Wloch M. K., Tonsky K., Norman J. other authors 2001; Vaxfectin enhances the humoral immune response to plasmid DNA-encoded antigens. Vaccine 19:1911–1923 [View Article][PubMed]
     [Google Scholar]
  21. Hermanson G., Whitlow V., Parker S., Tonsky K., Rusalov D., Ferrari M., Lalor P., Komai M., Mere R. other authors 2004; A cationic lipid-formulated plasmid DNA vaccine confers sustained antibody-mediated protection against aerosolized anthrax spores. Proc Natl Acad Sci U S A 101:13601–13606 [View Article][PubMed]
     [Google Scholar]
  22. Higgins T. J., Herold K. M., Arnold R. L., McElhiney S. P., Shroff K. E., Pachuk C. J. 2000; Plasmid DNA-expressed secreted and nonsecreted forms of herpes simplex virus glycoprotein D2 induce different types of immune responses. J Infect Dis 182:1311–1320 [View Article][PubMed]
     [Google Scholar]
  23. Hosken N., McGowan P., Meier A., Koelle D. M., Sleath P., Wagener F., Elliott M., Grabstein K., Posavad C., Corey L. 2006; Diversity of the CD8+ T-cell response to herpes simplex virus type 2 proteins among persons with genital herpes. J Virol 80:5509–5515 [View Article][PubMed]
     [Google Scholar]
  24. Iijima N., Linehan M. M., Zamora M., Butkus D., Dunn R., Kehry M. R., Laufer T. M., Iwasaki A. 2008; Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus. J Exp Med 205:3041–3052 [View Article][PubMed]
     [Google Scholar]
  25. Jimenez G. S., Planchon R., Wei Q., Rusalov D., Geall A., Enas J., Lalor P., Leamy V., Vahle R. other authors 2007; Vaxfectin-formulated influenza DNA vaccines encoding NP and M2 viral proteins protect mice against lethal viral challenge. Hum Vaccin 3:157–164 [View Article][PubMed]
     [Google Scholar]
  26. Jing L., McCaughey S. M., Davies D. H., Chong T. M., Felgner P. L., De Rosa S. C., Wilson C. B., Koelle D. M. 2009; ORFeome approach to the clonal, HLA allele-specific CD4 T-cell response to a complex pathogen in humans. J Immunol Methods 347:36–45 [View Article][PubMed]
     [Google Scholar]
  27. Kask A. S., Chen X., Marshak J. O., Dong L., Saracino M., Chen D., Jarrahian C., Kendall M. A., Koelle D. M. 2010; DNA vaccine delivery by densely-packed and short microprojection arrays to skin protects against vaginal HSV-2 challenge. Vaccine 28:7483–7491 [View Article][PubMed]
     [Google Scholar]
  28. Kemble G., Spaete R. 2007; Herpes simplex vaccines. In Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis chapter 69. Edited by Arvin A., Campadelli-Fiume G., Mocarski E., Moore P. S., Roizman B., Whitley R., Yamanishi K. Cambridge: Cambridge University Press;
     [Google Scholar]
  29. Kim M., Taylor J., Sidney J., Mikloska Z., Bodsworth N., Lagios K., Dunckley H., Byth-Wilson K., Denis M. other authors 2008; Immunodominant epitopes in herpes simplex virus type 2 glycoprotein D are recognized by CD4 lymphocytes from both HSV-1 and HSV-2 seropositive subjects. J Immunol 181:6604–6615[PubMed] [CrossRef]
     [Google Scholar]
  30. Klein R. J. 1980; Effect of immune serum on the establishment of herpes simplex virus infection in trigeminal ganglia of hairless mice. J Gen Virol 49:401–405 [View Article][PubMed]
     [Google Scholar]
  31. Koelle D. M., Corey L. 2008; Herpes simplex: insights on pathogenesis and possible vaccines. Annu Rev Med 59:381–395 [View Article][PubMed]
     [Google Scholar]
  32. Koelle D. M., Benedetti J., Langenberg A., Corey L. 1992; Asymptomatic reactivation of herpes simplex virus in women after the first episode of genital herpes. Ann Intern Med 116:433–437[PubMed] [CrossRef]
     [Google Scholar]
  33. Koelle D. M., Liu Z., McClurkan C. L., Cevallos R. C., Vieira J., Hosken N. A., Meseda C. A., Snow D. C., Wald A., Corey L. 2003; Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor. Proc Natl Acad Sci U S A 100:12899–12904 [View Article][PubMed]
     [Google Scholar]
  34. Langenberg A. G., Burke R. L., Adair S. F., Sekulovich R., Tigges M., Dekker C. L., Corey L. 1995; A recombinant glycoprotein vaccine for herpes simplex virus type 2: safety and immunogenicity [corrected]. Ann Intern Med 122:889–898[PubMed] [CrossRef]
     [Google Scholar]
  35. Long D., Madara T. J., Ponce de Leon M., Cohen G. H., Montgomery P. C., Eisenberg R. J. 1984; Glycoprotein D protects mice against lethal challenge with herpes simplex virus types 1 and 2. Infect Immun 43:761–764[PubMed]
     [Google Scholar]
  36. Malin S. A., Davis B. M., Molliver D. C. 2007; Production of dissociated sensory neuron cultures and considerations for their use in studying neuronal function and plasticity. Nat Protoc 2:152–160 [View Article][PubMed]
     [Google Scholar]
  37. Manickan E., Rouse R. J., Yu Z., Wire W. S., Rouse B. T. 1995; Genetic immunization against herpes simplex virus. Protection is mediated by CD4+ T lymphocytes. J Immunol 155:259–265[PubMed]
     [Google Scholar]
  38. Margalith M., Vilalta A. 2006; Sustained protective rabies neutralizing antibody titers after administration of cationic lipid-formulated pDNA vaccine. Genet Vaccines Ther 4:2 [View Article][PubMed]
     [Google Scholar]
  39. McClements W. L., Armstrong M. E., Keys R. D., Liu M. A. 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 [View Article][PubMed]
     [Google Scholar]
  40. Muller W. J., Dong L., Vilalta A., Byrd B., Wilhelm K. M., McClurkan C. L., Margalith M., Liu C., Kaslow D. other authors 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 [View Article][PubMed]
     [Google Scholar]
  41. Nass P. H., Elkins K. L., Weir J. P. 2001; Protective immunity against herpes simplex virus generated by DNA vaccination compared to natural infection. Vaccine 19:1538–1546 [View Article][PubMed]
     [Google Scholar]
  42. Pan C. H., Jimenez G. S., Nair N., Wei Q., Adams R. J., Polack F. P., Rolland A., Vilalta A., Griffin D. E. 2008; Use of Vaxfectin adjuvant with DNA vaccine encoding the measles virus hemagglutinin and fusion proteins protects juvenile and infant rhesus macaques against measles virus. Clin Vaccine Immunol 15:1214–1221 [View Article][PubMed]
     [Google Scholar]
  43. Parr M. B., Kepple L., McDermott M. R., Drew M. D., Bozzola J. J., Parr E. L. 1994; A mouse model for studies of mucosal immunity to vaginal infection by herpes simplex virus type 2. Lab Invest 70:369–380[PubMed]
     [Google Scholar]
  44. Perez G., Skurnick J. H., Denny T. N., Stephens R., Kennedy C. A., Regivick N., Nahmias A., Lee F. K., Lo S. C. other authors 1998; Herpes simplex type II and Mycoplasma genitalium as risk factors for heterosexual HIV transmission: report from the heterosexual HIV transmission study. Int J Infect Dis 3:5–11 [View Article][PubMed]
     [Google Scholar]
  45. Rajcáni J., Mosko T., Rezuchová I. 2005; Current developments in viral DNA vaccines: shall they solve the unsolved?. Rev Med Virol 15:303–325 [View Article][PubMed]
     [Google Scholar]
  46. Reyes L., Hartikka J., Bozoukova V., Sukhu L., Nishioka W., Singh G., Ferrari M., Enas J., Wheeler C. J. other authors 2001; Vaxfectin enhances antigen specific antibody titers and maintains Th1 type immune responses to plasmid DNA immunization. Vaccine 19:3778–3786 [View Article][PubMed]
     [Google Scholar]
  47. Sawtell N. M. 1998; The probability of in vivo reactivation of herpes simplex virus type 1 increases with the number of latently infected neurons in the ganglia. J Virol 72:6888–6892[PubMed]
     [Google Scholar]
  48. Sawtell N. M., Poon D. K., Tansky C. S., Thompson R. L. 1998; The latent herpes simplex virus type 1 genome copy number in individual neurons is virus strain specific and correlates with reactivation. J Virol 72:5343–5350[PubMed]
     [Google Scholar]
  49. Sawtell N. M., Thompson R. L., Stanberry L. R., Bernstein D. I. 2001; Early intervention with high-dose acyclovir treatment during primary herpes simplex virus infection reduces latency and subsequent reactivation in the nervous system in vivo. J Infect Dis 184:964–971 [View Article][PubMed]
     [Google Scholar]
  50. Shiver J. W., Fu T. M., Chen L., Casimiro D. R., Davies M. E., Evans R. K., Zhang Z. Q., Simon A. J., Trigona W. L. other authors 2002; Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 415:331–335 [View Article][PubMed]
     [Google Scholar]
  51. Simmons A., Nash A. A. 1985; Role of antibody in primary and recurrent herpes simplex virus infection. J Virol 53:944–948[PubMed]
     [Google Scholar]
  52. Sin J. I., Ayyavoo V., Boyer J., Kim J., Ciccarelli R. B., Weiner D. B. 1999; Protective immune correlates can segregate by vaccine type in a murine herpes model system. Int Immunol 11:1763–1773 [View Article][PubMed]
     [Google Scholar]
  53. Sin J., Kim J. J., Pachuk C., Satishchandran C., Weiner D. B. 2000; DNA vaccines encoding interleukin-8 and RANTES enhance antigen-specific Th1-type CD4+ T-cell-mediated protective immunity against herpes simplex virus type 2 in vivo. J Virol 74:11173–11180 [View Article][PubMed]
     [Google Scholar]
  54. Sin J. I., Kim J. J., Zhang D., Weiner D. B. 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 [View Article][PubMed]
     [Google Scholar]
  55. Smith L. R., Wloch M. K., Ye M., Reyes L. R., Boutsaboualoy S., Dunne C. E., Chaplin J. A., Rusalov D., Rolland A. P. other authors 2010; Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin. Vaccine 28:2565–2572 [View Article][PubMed]
     [Google Scholar]
  56. Stanberry L. R., Spruance S., Cunningham A. L., Bernstein D. I., Mindel A., Sacks S., Tyring S., Aoki F. Y., Slaoui M. other authors 2002; Glycoprotein-D–adjuvant vaccine to prevent genital herpes. N Engl J Med 347:1652–1661 [View Article][PubMed]
     [Google Scholar]
  57. Sullivan S. M., Doukas J., Hartikka J., Smith L., Rolland A. 2010; Vaxfectin: a versatile adjuvant for plasmid DNA- and protein-based vaccines. Expert Opin Drug Deliv 7:1433–1446 [View Article][PubMed]
     [Google Scholar]
  58. Ulmer J. B., DeWitt C. M., Chastain M., Friedman A., Donnelly J. J., McClements W. L., Caulfield M. J., Bohannon K. E., Volkin D. B., Evans R. K. 1999; Enhancement of DNA vaccine potency using conventional aluminum adjuvants. Vaccine 18:18–28 [View Article][PubMed]
     [Google Scholar]
  59. Vilalta A., Shlapobersky M., Wei Q., Planchon R., Rolland A., Sullivan S. 2009; Analysis of biomarkers after intramuscular injection of Vaxfectin-formulated hCMV gB plasmid DNA. Vaccine 27:7409–7417 [View Article][PubMed]
     [Google Scholar]
  60. Wald A., Corey L. 2003; How does herpes simplex virus type 2 influence human immunodeficiency virus infection and pathogenesis?. J Infect Dis 187:1509–1512 [View Article][PubMed]
     [Google Scholar]
  61. Wald A., Zeh J., Selke S., Warren T., Ashley R., Corey L. 2002; Genital shedding of herpes simplex virus among men. J Infect Dis 186:Suppl. 1S34–S39 [View Article][PubMed]
     [Google Scholar]
  62. Wald A., Huang M. L., Carrell D., Selke S., Corey L. 2003; Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis 188:1345–1351 [View Article][PubMed]
     [Google Scholar]
  63. Watson R. J. 1983; DNA sequence of the herpes simplex virus type 2 glycoprotein D gene. Gene 26:307–312 [View Article][PubMed]
     [Google Scholar]
  64. Xu F., Sternberg M. R., Kottiri B. J., McQuillan G. M., Lee F. K., Nahmias A. J., Berman S. M., Markowitz L. E. 2006; Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA 296:964–973 [View Article][PubMed]
     [Google Scholar]
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Vaxfectin-adjuvanted plasmid DNA vaccine improves protection and immunogenicity in a murine model of genital herpes infection
J. Gen. Virol. 93, 1305 (2012); https://doi.org/10.1099/vir.0.040055-0
/content/journal/jgv/10.1099/vir.0.040055-0
/content/journal/jgv/10.1099/vir.0.040055-0
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