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Vol. 54, No. 3, 2008
Issue release date: July 2008
Chemotherapy 2008;54:176–180

Potent in vitro Activity of the Albumin Fusion Type 1 Interferons (Albumin-Interferon-Alpha and Albumin-Interferon-Beta) against RNA Viral Agents of Bioterrorism and the Severe Acute Respiratory Syndrome (SARS) Virus

Subramanian G.M. · Moore P.A. · Gowen B.B. · Olsen A.L. · Barnard D.L. · Paragas J. · Hogan R.J. · Sidwell R.W.
aHuman Genome Sciences, Inc., Rockville, Md., bInstitute of Antiviral Research, Utah State University, Logan, Utah, cUS Army Medical Research Institute of Infectious Diseases, Fort Detrick, Md., and dUniversity of Georgia, Athens, Ga., USA

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Background: The type 1 interferons (INF-α and INF-β) are potent antiviral agents. Albumin-INF-α and albumin-INF-β are novel recombinant proteins consisting of IFN-α or IFN-β genetically fused to human albumin. Methods: The in vitro antiviral activity of albumin-IFN-α was evaluated against representative bioterrorism viral agents and the severe acute respiratory syndrome virus. Antiviral activity was assessed using inhibition of cytopathic effect and neutral red staining. Results: EC50 values for albumin-IFN-α ranged from <0.1 ng/ml for Punta Toro virus to 65 ng/ml for Venezuelan equine encephalitis virus in the neutral red assay. Albumin-IFN-β showed 75- and 360-fold greater in vitro activity than albumin-IFN-α against Ebola virus and severe acute respiratory syndrome, respectively. Conclusion: Further evaluation of these long-acting albumin-IFN fusion proteins as prophylactic or therapeutic agents against these viral agents of bioterrorism in relevant primate models is warranted.

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  1. Borio L, Inglesby T, Peters CJ, Schmaljohn AL, Hughes JM, Jahrling PB, Ksiazek T, Johnson KM, Meyerhoff A, O’Toole T, Ascher MS, Bartlett J, Breman JG, Eitzen EM Jr, Hamburg M, Hauer J, Henderson DA, Johnson RT, Kwik G, Layton M, Lillibridge S, Nabel GJ, Osterholm MT, Perl TM, Russell P, Tonat K: Working Group on Civilian Biodefense. Hemorrhagic fever viruses as biological weapons: medical and public health management. JAMA 2002;287:2391–2405.
  2. Bronze MS, Huycke MM, Machado LJ, Voskuhl GW, Greenfield RA: Viral agents as biological weapons and agents of bioterrorism. Am J Med Sci 2002;323:316–325.
  3. Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, Tong S, Urbani C, Comer JA, Lim W, Rollin PE, Dowell SF, Ling AE, Humphrey CD, Shieh WJ, Guarner J, Paddock CD, Rota P, Fields B, DeRisi J, Yang JY, Cox N, Hughes JM, LeDuc JW, Bellini WJ, Anderson LJ, SARS Working Group: A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003;348:1953–1966.
  4. Subramanian GM, Fiscella M, Lamousé-Smith A, Zeuzem S, McHutchison JG: Albinterferon alpha-2b, a novel therapy for chronic hepatitis C virus infection. Nat Biotechnol 2007;25:1411–1419.
  5. Akhan SC, Yulugkural Z, Vahaboglu H: Response to interferon-alpha in chronic hepatitis B patients with and without precore mutant strain and effects on HBsAg titers. Chemotherapy 2007;53:402–406.
  6. Samuel CE: Antiviral actions of interferon. Interferon-regulated cellular proteins and their surprisingly selective antiviral activities. Virology 1991;183:1–11.
  7. Osborn BL, Olsen HS, Nardelli B, Murray JH, Zhou JX, Garcia A, Moody G, Zaritskaya LS, Sung C: Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-alpha fusion protein in cynomolgus monkeys. J Pharmacol Exp Ther 2002;303:540–548.
  8. Bain VG, Kaita KD, Yoshida EM, Swain MG, Heathcote EJ, Neumann AU, Fiscella M, Yu R, Osborn BL, Cronin PW, Freimuth WW, McHutchison JG, Subramanian GM: A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients. J Hepatol 2006;44:671–678.
  9. Bain VG, Yoshida EM, Kaita KD, Swain MG, Heathcote EJ, Garcia A, Moore PA, Yu R, McHutchison JG, Subramanian GM: Dynamics of interferon-specific gene expression in peripheral blood of interferon alfa-naive patients with genotype 1 chronic hepatitis C infection treated with albumin-interferon alfa. Hepatol Res 2006;35:256–262.
  10. Balan V, Nelson DR, Sulkowski MS, Everson GT, Lambiase LR, Wiesner RH, Dickson RC, Post AB, Redfield RR, Davis GL, Neumann AU, Osborn BL, Freimuth WW, Subramanian GM: A phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy. Antivir Ther 2006;11:35–45.
  11. Sung C, Nardelli B, LaFleur DW, Blatter E, Corcoran M, Olsen HS, Birse CE, Pickeral OK, Zhang J, Shah D, Moody G, Gentz S, Beebe L, Moore PA: An IFN-beta-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates. J Interferon Cytokine Res 2003;23:25–36.
  12. Smee DF, Morrison AC, Barnard DL, Sidwell RW: Comparison of colorimetric, fluorometric, and visual methods for determining anti-influenza (H1N1 and H3N2) virus activities and toxicities of compounds. J Virol Methods 2002;106:71–79.
  13. Towner JS, Paragas J, Dover JE, Gupta M, Goldsmith CS, Huggins JW, Nichol ST: Generation of eGFP expressing recombinant Zaire ebolavirus for analysis of early pathogenesis events and high-throughput antiviral drug screening. Virology 2005;332:20–27.
  14. Canonico PG, Kende M, Luscri BJ, Huggins JW: In-vivo activity of antivirals against exotic RNA viral infections. J Antimicrob Chemother 1984;14A:27–41.
  15. Smee DF, Bailey KW, Morrison AC, Sidwell RW: Combination treatment of influenza A virus infections in cell culture and in mice with the cyclopentane neuraminidase inhibitor RWJ-270201 and ribavirin. Chemotherapy 2002;48:88–93.
  16. Sidwell RW, Smee DF: Viruses of the Bunya- and Togaviridae families: potential as bioterrorism agents and means of control. Antiviral Res 2003;57:101–111.
  17. Haagmans BL, Kuiken T, Martina BE, Fouchier RA, Rimmelzwaan GF, van Amerongen G, van Riel D, de Jong T, Itamura S, Chan KH, Tashiro M, Osterhaus AD: Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nat Med 2004;10:290–293.
  18. Loutfy MR, Blatt LM, Siminovitch KA, Ward S, Wolff B, Lho H, Pham DH, Deif H, LaMere EA, Chang M, Kain KC, Farcas GA, Ferguson P, Latchford M, Levy G, Dennis JW, Lai EK, Fish EN: Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. JAMA 2003;290:3222–3228.
  19. Stroher U, DiCaro A, Li Y, Strong JE, Aoki F, Plummer F, Jones SM, Feldmann H: Severe acute respiratory syndrome-related coronavirus is inhibited by interferon-alpha. J Infect Dis 2004;189:1164–1167.
  20. Dahl H, Linde A, Strannegard O: In vitro inhibition of SARS virus replication by human interferons. Scand J Infect Dis 2004;36:829–831.
  21. Morgenstern B, Michaelis M, Baer PC, Doerr HW, Cinatl J: Ribavirin and interferon-beta synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines. Biochem Biophys Res Commun 2005;326:905–908.
  22. Jahrling PB, Geisbert TW, Geisbert JB, Swearengen JR, Bray M, Jaax NK, Huggins JW, LeDuc JW, Peters CJ: Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections. J Infect Dis 1999;179:S224–S234.

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