Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with smallpox vaccine does not compromise vaccine protection in mice challenged with ectromelia virus

Antiviral Research

Volumn 111, Issue , 2014, Pages 42-52

  Parker, Scott ^a   Crump, Ryan ^a   Foster, Scott ^b   Hartzler, Hollyce ^a,c   Hembrador, Ed ^a   Lanier, E Randall ^b   Painter, George ^b,d   Schriewer, Jill ^a,e   Trost, Lawrence C ^b   Buller, R Mark ^a  

^a SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Chimerix Inc   (United States)

^c Cardiothoracic Surgery Research Laboratories   (United States)

^d EMORY UNIVERSITY   (United States)

^e KCUMB Department of Pharmacology and Microbiology   (United States)

Author keywords

ACAM2000; ACAM3000; Cidofovir; Dryvax; Mousepox; MVA

Indexed keywords

BRINCIDOFOVIR; CIDOFOVIR; SMALLPOX VACCINE; ANTIVIRUS AGENT; CYTOSINE; PHOSPHONIC ACID DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; ECTROMELIA VIRUS; FEMALE; HEALING; IMMUNE RESPONSE; IMMUNE SYSTEM; MOUSE; MOUSEPOX; NONHUMAN; POST EXPOSURE PROPHYLAXIS; TREATMENT DURATION; VACCINATION; VIRUS REPLICATION; ANALOGS AND DERIVATIVES; ANIMAL; C57BL MOUSE; ECTROMELIA, INFECTIOUS; HUMAN; IMMUNITY; IMMUNOLOGY; PHYSIOLOGY; VIROLOGY;

ECTROMELIA VIRUS; MUS; VARIOLA VIRUS;

ANIMALS; ANTIVIRAL AGENTS; CYTOSINE; ECTROMELIA VIRUS; ECTROMELIA, INFECTIOUS; FEMALE; HUMANS; IMMUNITY; MICE; MICE, INBRED C57BL; ORGANOPHOSPHONATES; SMALLPOX VACCINE; VACCINATION; VIRUS REPLICATION;

EID: 84907504812     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2014.08.003     Document Type: Article

References (71)

1. A. Berhanu, D.S. King, S. Mosier, R. Jordan, K.F. Jones, D.E. Hruby, and D.W. Grosenbach ST-246 inhibits in vivo poxvirus dissemination, virus shedding, and systemic disease manifestation Antimicrob. Agents Chemother. 53 2009 4999 5009
2. A. Berhanu, D.S. King, S. Mosier, R. Jordan, K.F. Jones, D.E. Hruby, and D.W. Grosenbach Impact of ST-246(R) on ACAM2000 smallpox vaccine reactogenicity, immunogenicity, and protective efficacy in immunodeficient mice Vaccine 29 2010 289 303
3. R.M. Buller, G. Owens, J. Schriewer, L. Melman, J.R. Beadle, and K.Y. Hostetler Efficacy of oral active ether lipid analogs of cidofovir in a lethal mousepox model Virology 318 2004 474 481
4. R.L. Buller, L. Handley, and S. Parker Development of prophylactics and therapeutics against the smallpox and monkeypox biothreat agents V. St. Georgiew, K. Wester, J. McGowan, National Institute of Allergy and Infectious Disease: Frontiers in Research 2008 Humana Press 145 161
5. W. Chen, R. Drillien, D. Spehner, and R.M. Buller Restricted replication of ectromelia virus in cell culture correlates with mutations in virus-encoded host range gene Virology 187 1992 433 442
6. N. Chen, C.J. Bellone, J. Schriewer, G. Owens, T. Fredrickson, S. Parker, and R.M. Buller Poxvirus interleukin-4 expression overcomes inherent resistance and vaccine-induced immunity: pathogenesis, prophylaxis, and antiviral therapy Virology 409 2011 328 337
7. S.L. Ciesla, J. Trahan, W.B. Wan, J.R. Beadle, K.A. Aldern, G.R. Painter, and K.Y. Hostetler Esterification of cidofovir with alkoxyalkanols increases oral bioavailability and diminishes drug accumulation in kidney Antiviral Res. 59 2003 163 171
8. E. De Clercq Cidofovir in the treatment of poxvirus infections Antiviral Res. 55 2002 1 13
9. S. Duraffour, R. Snoeck, R. de Vos, J.J. van Den Oord, J.M. Crance, D. Garin, D.E. Hruby, R. Jordan, E. De Clercq, and G. Andrei Activity of the anti-orthopoxvirus compound ST-246 against vaccinia, cowpox and camelpox viruses in cell monolayers and organotypic raft cultures Antivir. Ther. 12 2007 1205 1216
10. P.L. Earl, J.L. Americo, L.S. Wyatt, L.A. Eller, J.C. Whitbeck, G.H. Cohen, R.J. Eisenberg, C.J. Hartmann, D.L. Jackson, D.A. Kulesh, M.J. Martinez, D.M. Miller, E.M. Mucker, J.D. Shamblin, S.H. Zwiers, J.W. Huggins, P.B. Jahrling, and B. Moss Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox Nature 428 2004 182 185
11. P.L. Earl, J.L. Americo, L.S. Wyatt, O. Espenshade, J. Bassler, K. Gong, S. Lin, E. Peters, L. Rhodes Jr., Y.E. Spano, P.M. Silvera, and B. Moss Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virus Proc. Natl. Acad. Sci. USA 105 2008 10889 10894
12. Y. Edghill-Smith, H. Golding, J. Manischewitz, L.R. King, D. Scott, M. Bray, A. Nalca, J.W. Hooper, C.A. Whitehouse, J.E. Schmitz, K.A. Reimann, and G. Franchini Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus Nat. Med. 11 2005 740 747
13. D. Esteban, S. Parker, J. Schriewer, H. Hartzler, and R.M. Buller Mousepox, a small animal model of smallpox Methods Mol. Biol. 890 2012 177 198
14. M. Fang, H. Cheng, Z. Dai, Z. Bu, and L.J. Sigal Immunization with a single extracellular enveloped virus protein produced in bacteria provides partial protection from a lethal orthopoxvirus infection in a natural host Virology 345 2006 231 243
15. F. Fenner, D.A. Henderson, I. Arita, Z. Jezek, and I.D. Ladnyi Smallpox and its eradication 1988 World Health Organisation Geneva
16. C. Fogg, S. Lustig, J.C. Whitbeck, R.J. Eisenberg, G.H. Cohen, and B. Moss Protective immunity to vaccinia virus induced by vaccination with multiple recombinant outer membrane proteins of intracellular and extracellular virions J. Virol. 78 2004 10230 10237
17. S.E. Frey, R.B. Couch, C.O. Tacket, J.J. Treanor, M. Wolff, F.K. Newman, R.L. Atmar, R. Edelman, C.M. Nolan, and R.B. Belshe Clinical responses to undiluted and diluted smallpox vaccine N. Engl. J. Med. 346 2002 1265 1274
18. S.E. Frey, F.K. Newman, J.S. Kennedy, V. Sobek, F.A. Ennis, H. Hill, L.K. Yan, P. Chaplin, J. Vollmar, B.R. Chaitman, and R.B. Belshe Clinical and immunologic responses to multiple doses of IMVAMUNE (Modified Vaccinia Ankara) followed by Dryvax challenge Vaccine 25 2007 8562 8573
19. N.L. Garza, J.M. Hatkin, V. Livingston, D.K. Nichols, P.J. Chaplin, A. Volkmann, D. Fisher, and A. Nalca Evaluation of the efficacy of modified vaccinia Ankara (MVA)/IMVAMUNE against aerosolized rabbitpox virus in a rabbit model Vaccine 27 2009 5496 5504
20. D.W. Grosenbach, R. Jordan, D.S. King, A. Berhanu, T.K. Warren, D.L. Kirkwood-Watts, S. Tyavanagimatt, Y. Tan, R.L. Wilson, K.F. Jones, and D.E. Hruby Immune responses to the smallpox vaccine given in combination with ST-246, a small-molecule inhibitor of poxvirus dissemination Vaccine 26 2008 933 946
21. D.W. Grosenbach, A. Berhanu, D.S. King, S. Mosier, K.F. Jones, R.A. Jordan, T.C. Bolken, and D.E. Hruby Efficacy of ST-246 versus lethal poxvirus challenge in immunodeficient mice Proc. Natl. Acad. Sci. USA 107 2010 838 843
22. L.M. Handley, J.P. Mackey, R.M.L. Buller, and C.J. Bellone Orthopoxvirus Vaccines and Vaccination 2007 Birkhauser Basel pp. 329-353
23. L. Handley, R.M. Buller, S.E. Frey, C. Bellone, and S. Parker The new ACAM2000 vaccine and other therapies to control orthopoxvirus outbreaks and bioterror attacks Expert Rev. Vaccines 8 2009 841 850
24. J.M. Heraud, Y. Edghill-Smith, V. Ayala, I. Kalisz, J. Parrino, V.S. Kalyanaraman, J. Manischewitz, L.R. King, A. Hryniewicz, C.J. Trindade, M. Hassett, W.P. Tsai, D. Venzon, A. Nalca, M. Vaccari, P. Silvera, M. Bray, B.S. Graham, H. Golding, J.W. Hooper, and G. Franchini Subunit recombinant vaccine protects against monkeypox J. Immunol. 177 2006 2552 2564
25. L.A. Hirao, R. Draghia-Akli, J.T. Prigge, M. Yang, A. Satishchandran, L. Wu, E. Hammarlund, A.S. Khan, T. Babas, L. Rhodes, P. Silvera, M. Slifka, N.Y. Sardesai, and D.B. Weiner Multivalent smallpox DNA vaccine delivered by intradermal electroporation drives protective immunity in nonhuman primates against lethal monkeypox challenge J. Infect. Dis. 203 2011 95 102
26. J.W. Hooper, D.M. Custer, C.S. Schmaljohn, and A.L. Schmaljohn DNA vaccination with vaccinia virus L1R and A33R genes protects mice against a lethal poxvirus challenge Virology 266 2000 329 339
27. J.W. Hooper, E. Thompson, C. Wilhelmsen, M. Zimmerman, M.A. Ichou, S.E. Steffen, C.S. Schmaljohn, A.L. Schmaljohn, and P.B. Jahrling Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox J. Virol. 78 2004 4433 4443
28. K.Y. Hostetler Synthesis and antiviral evaluation of broad spectrum, orally active analogs of cidofovir and other acyclic nucleoside phosphonates E. De Clercq, Advances in Antiviral Drug Design vol. 5 2007 Elsevir 167 184
29. T. Israely, N. Paran, S. Lustig, N. Erez, B. Politi, A. Shafferman, and S. Melamed A single cidofovir treatment rescues animals at progressive stages of lethal orthopoxvirus disease Virol. J. 9 2012 119
30. R.J. Jackson, D.J. Maguire, L.A. Hinds, and I.A. Ramshaw Infertility in mice induced by a recombinant ectromelia virus expressing mouse zona pellucida glycoprotein 3 Biol. Reprod. 58 1998 152 159
31. R.J. Jackson, A.J. Ramsay, C.D. Christensen, S. Beaton, D.F. Hall, and I.A. Ramshaw Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox J. Virol. 75 2001 1205 1210
32. R. Jordan, D. Tien, T.C. Bolken, K.F. Jones, T.R. Shanthakumar, J. Strasser, A. Frimm, M.L. Corrado, P.G. Strome, and D.E. Hruby Single-dose safety and pharmacokinetics of ST-246, a novel orthopoxvirus egress inhibitor Antimicrob. Agents Chemother. 52 5 2008 1721 1727
33. M.S. Keckler, M.G. Reynolds, I.K. Damon, and K.L. Karem The effects of post-exposure smallpox vaccination on clinical disease presentation: addressing the data gaps between historical epidemiology and modern surrogate model data Vaccine 31 2013 5192 5201
34. A.R. Kemper, M.M. Davis, and G.L. Freed Expected adverse events in a mass smallpox vaccination campaign Eff. Clin. Pract. 5 2002 84 90
35. J.S. Kennedy, M. Gurwith, C.L. Dekker, S.E. Frey, K.M. Edwards, J. Kenner, M. Lock, C. Empig, S. Morikawa, M. Saijo, H. Yokote, K. Karem, I. Damon, M. Perlroth, and R.N. Greenberg Safety and immunogenicity of LC16m8, an attenuated smallpox vaccine in vaccinia-naive adults J. Infect. Dis. 204 2011 1395 1402
36. R. Lanier, L. Trost, T. Tippin, B. Lampert, A. Robertson, S. Foster, M. Rose, W. Painter, R. O'Mahony, M. Almond, and G. Painter Development of CMX001 for the treatment of poxvirus infections Viruses 2 2010 2740 2762
37. E. Lederman, R. Miramontes, J. Openshaw, V.A. Olson, K.L. Karem, J. Marcinak, R. Panares, W. Staggs, D. Allen, S.G. Weber, S. Vora, S.I. Gerber, C.M. Hughes, R. Regnery, L. Collins, P.S. Diaz, M.G. Reynolds, and I. Damon Eczema vaccinatum resulting from the transmission of vaccinia virus from a smallpox vaccinee: an investigation of potential fomites in the home environment Vaccine 27 2009 375 377
38. E.R. Lederman, W. Davidson, H.L. Groff, S.K. Smith, T. Warkentien, Y. Li, K.A. Wilkins, K.L. Karem, R.S. Akondy, R. Ahmed, M. Frace, W.J. Shieh, S. Zaki, D.E. Hruby, W.P. Painter, K.L. Bergman, J.I. Cohen, and I.K. Damon Progressive vaccinia: case description and laboratory-guided therapy with vaccinia immune globulin, ST-246, and CMX001 J. Infect. Dis. 206 2012 1372 1385
39. B. Moss, and P.L. Earl Expression of proteins in mammalian cells using vaccinia cirus vectors. Overview of the vaccinia virus expression system Current Protocols in Molecular Biology 1998 Wiley 16.15.11 16.15.15
40. E.M. Mucker, A.J. Goff, J.D. Shamblin, D.W. Grosenbach, I.K. Damon, J.M. Mehal, R.C. Holman, D. Carroll, N. Gallardo, V.A. Olson, C.J. Clemmons, P. Hudson, and D.E. Hruby Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox) Antimicrob. Agents Chemother. 57 2013 6246 6253
41. E. Munz, S. Linckh, I.C. Renner-Muller, and M. Reimann The effectiveness of immunization with vaccinia virus type "MVA" against an infection with cowpox virus type "OPV 85" in rabbits Zentralbl. Veterinarmed. B 40 1993 131 140
42. A. Nalca, and E.E. Zumbrun ACAM2000: the new smallpox vaccine for United States Strategic National Stockpile Drug Des. Dev. Ther. 4 2010 71 79
43. A. Nalca, J.M. Hatkin, N.L. Garza, D.K. Nichols, S.W. Norris, D.E. Hruby, and R. Jordan Evaluation of orally delivered ST-246 as postexposure prophylactic and antiviral therapeutic in an aerosolized rabbitpox rabbit model Antiviral Res. 79 2008 121 127
44. J. Neyts, P. Leyssen, E. Verbeken, and E. De Clercq Efficacy of cidofovir in a murine model of disseminated progressive vaccinia Antimicrob. Agents Chemother. 48 2004 2267 2273
45. N. Paran, Y. Suezer, S. Lustig, T. Israely, A. Schwantes, S. Melamed, L. Katz, T. Preuss, K.M. Hanschmann, U. Kalinke, N. Erez, R. Levin, B. Velan, J. Lower, A. Shafferman, and G. Sutter Postexposure immunization with modified vaccinia virus Ankara or conventional Lister vaccine provides solid protection in a murine model of human smallpox J. Infect. Dis. 199 2009 39 48
46. S. Parker, and R.M. Buller A review of experimental and natural infections of animals with monkeypox virus between 1958 and 2012 Future Virol. 8 2013 129 157
47. S. Parker, A. Nuara, R.M. Buller, and D.A. Schultz Human monkeypox: an emerging zoonotic disease Future Microbiol. 2 2007 17 34
48. S. Parker, L. Handley, and R.M. Buller Therapeutic and prophylactic drugs to treat orthopoxvirus infections Future Virol. 3 2008 595 612
49. S. Parker, J. Schriewer, C. Oberle, A. Robertson, R. Lanier, G. Painter, and R.M. Buller Using biomarkers to stage disease progression in a lethal mousepox model treated with CMX001 Antivir. Ther. 13 2008 863 873
50. S. Parker, E. Touchette, C. Oberle, M. Almond, A. Robertson, L.C. Trost, B. Lampert, G. Painter, and R.M. Buller Efficacy of therapeutic intervention with an oral ether-lipid analogue of cidofovir (CMX001) in a lethal mousepox model Antiviral Res. 77 2008 39 49
51. S. Parker, A.M. Siddiqui, C. Oberle, E. Hembrador, R. Lanier, G. Painter, A. Robertson, and R.M. Buller Mousepox in the C57BL/6 strain provides an improved model for evaluating anti-poxvirus therapies Virology 385 2009 11 21
52. S. Parker, A.M. Siddiqui, G. Painter, J. Schriewer, and R.M. Buller Ectromelia virus infections of mice as a model to support the licensure of anti-orthopoxvirus therapeutics Viruses 2 2010 1918 1932
53. D.J. Pulford, A. Gates, S.H. Bridge, J.H. Robinson, and D. Ulaeto Differential efficacy of vaccinia virus envelope proteins administered by DNA immunisation in protection of BALB/c mice from a lethal intranasal poxvirus challenge Vaccine 22 2004 3358 3366
54. D.C. Quenelle, D.J. Collins, and E.R. Kern Efficacy of multiple- or single-dose cidofovir against vaccinia and cowpox virus infections in mice Antimicrob. Agents Chemother. 47 2003 3275 3280
55. D.C. Quenelle, D.J. Collins, W.B. Wan, J.R. Beadle, K.Y. Hostetler, and E.R. Kern Oral treatment of cowpox and vaccinia virus infections in mice with ether lipid esters of cidofovir Antimicrob. Agents Chemother. 48 2004 404 412
56. D.C. Quenelle, R.M. Buller, S. Parker, K.A. Keith, D.E. Hruby, R. Jordan, and E.R. Kern Efficacy of delayed treatment with ST-246 given orally against systemic orthopoxvirus infections in mice Antimicrob. Agents Chemother. 51 2007 689 695
57. D.C. Quenelle, D.J. Collins, B.P. Herrod, K.A. Keith, J. Trahan, J.R. Beadle, K.Y. Hostetler, and E.R. Kern Effect of oral treatment with hexadecyloxypropyl-[(S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine] [(S)-HPMPA] or octadecyloxyethyl-(S)-HPMPA on cowpox or vaccinia virus infections in mice Antimicrob. Agents Chemother. 51 2007 3940 3947
58. D.C. Quenelle, M.N. Prichard, K.A. Keith, D.E. Hruby, R. Jordan, G.R. Painter, A. Robertson, and E.R. Kern Synergistic efficacy of the combination of ST-246 with CMX001 against orthopoxviruses Antimicrob. Agents Chemother. 51 2007 4118 4124
59. S.J. Robbins, R.J. Jackson, F. Fenner, S. Beaton, J. Medveczky, I.A. Ramshaw, and A.J. Ramsay The efficacy of cidofovir treatment of mice infected with ectromelia (mousepox) virus encoding interleukin-4 Antiviral Res. 66 2005 1 7
60. S.R. Rosenthal, M. Merchlinsky, C. Kleppinger, and K.L. Goldenthal Developing new smallpox vaccines Emerg. Infect. Dis. 7 2001 920 926
61. Silvera, P.M., Peter, E., Bassler, J., Gong, G., Lin, S., Hebblewaite, D., 2009. Impact of concurrent ST-246 administration on ACAM2000 vaccine efficacy in cynomolgus macaques. In: 7th ASM Biodefense Emerging Dis. Res. Meet.
62. D.F. Smee, K.W. Bailey, M.H. Wong, and R.W. Sidwell Effects of cidofovir on the pathogenesis of a lethal vaccinia virus respiratory infection in mice Antiviral Res. 52 2001 55 62
63. D.F. Smee, R.W. Sidwell, D. Kefauver, M. Bray, and J.W. Huggins Characterization of wild-type and cidofovir-resistant strains of camelpox, cowpox, monkeypox, and vaccinia viruses Antimicrob. Agents Chemother. 46 2002 1329 1335
64. D.F. Smee, K.W. Bailey, M.H. Wong, M.K. Wandersee, and R.W. Sidwell Topical cidofovir is more effective than is parenteral therapy for treatment of progressive vaccinia in immunocompromised mice J. Infect. Dis. 190 2004 1132 1139
65. S.K. Smith, J. Self, S. Weiss, D. Carroll, Z. Braden, R.L. Regnery, W. Davidson, R. Jordan, D.E. Hruby, and I.K. Damon Effective antiviral treatment of systemic orthopoxvirus disease: ST-246 treatment of prairie dogs infected with monkeypox virus J. Virol. 85 2011 9176 9187
66. J.T. Snyder, I.M. Belyakov, A. Dzutsev, F. Lemonnier, and J.A. Berzofsky Protection against lethal vaccinia virus challenge in HLA-A2 transgenic mice by immunization with a single CD8+ T-cell peptide epitope of vaccinia and variola viruses J. Virol. 78 2004 7052 7060
67. J. Stabenow, R.M. Buller, J. Schriewer, C. West, J.E. Sagartz, and S. Parker A mouse model of lethal infection for evaluating prophylactics and therapeutics against Monkeypox virus J. Virol. 84 2010 3909 3920
68. J. Vollmar, N. Arndtz, K.M. Eckl, T. Thomsen, B. Petzold, L. Mateo, B. Schlereth, A. Handley, L. King, V. Hulsemann, M. Tzatzaris, K. Merkl, N. Wulff, and P. Chaplin Safety and immunogenicity of IMVAMUNE, a promising candidate as a third generation smallpox vaccine Vaccine 24 2006 2065 2070
69. G.D. Wallace, and R.M. Buller Kinetics of ectromelia virus (mousepox) transmission and clinical response in C57BL/6j, BALB/cByj and AKR/J inbred mice Lab. Anim. Sci. 35 1985 41 46
70. H. Wei, D. Huang, J. Fortman, R. Wang, L. Shao, and Z.W. Chen Coadministration of cidofovir and smallpox vaccine reduced vaccination side effects but interfered with vaccine-elicited immune responses and immunity to monkeypox J. Virol. 83 2009 1115 1125
71. G. Yang, D.C. Pevear, M.H. Davies, M.S. Collett, T. Bailey, S. Rippen, L. Barone, C. Burns, G. Rhodes, S. Tohan, J.W. Huggins, R.O. Baker, R.L. Buller, E. Touchette, K. Waller, J. Schriewer, J. Neyts, E. DeClercq, K. Jones, D. Hruby, and R. Jordan An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus challenge J. Virol. 79 2005 13139 13149