Publications describing technology licensed by Profectus BioSciences:

Immunotherapeutics

Heredia A, Davis C, Bamba D, Le N, Gwarzo MY, Sadowska M, Gallo RC, Redfield RR.  Indirubin-3'-monoxime, a derivative of a Chinese anti-leukemia medicine, inhibits P-TEFb function and HIV-1 replication. AIDS. 2005. 19(18):2087-95.

Heredia A, Davis C, Amoroso A, Taylor G, Le N, Bamba D, Redfield RR.  In vitro suppression of latent HIV-1 activation by vitamin E: potential clinical implications. AIDS. 2005. 19(8):836-7.

Heredia A, Amoroso A, Davis C, Le N, Reardon E, Dominique JK, Klingebiel E, Gallo RC, Redfield RR.  Rapamycin causes down-regulation of CCR5 and accumulation of anti-HIV beta-chemokines: an approach to suppress R5 strains of HIV-1. Proc Natl Acad Sci U S A. 2003. 100(18):10411-6.

Heredia A, Davis C, Amoroso A, Dominique JK, Le N, Klingebiel E, Reardon E, Zella D, Redfield RR. Induction of G1 cycle arrest in T lymphocytes results in increased extracellular levels of beta-chemokines: a strategy to inhibit R5 HIV-1. Proc Natl Acad Sci U S A. 2003. 100(7):4179-84.

Davis C, Heredia A, Le N, Dominique JK, Redfield RR. Differential human immunodeficiency virus-suppressive activity of reverse transcription inhibitors in resting and activated peripheral blood lymphocytes: implications for therapy.  J Hum Virol. 2001.  4(3):113-22.

Heredia A, Davis C, Redfield R.Synergistic inhibition of HIV-1 in activated and resting peripheral blood mononuclear cells, monocyte-derived macrophages, and selected drug-resistant isolates with nucleoside analogues combined with a natural product, resveratrol.   J Acquir Immune Defic Syndr. 2000. 25(3):246-55.

Heredia A, Latinovic O, Gallo RC, Melikyan G, Reitz M, Le N, Redfield RR. Reduction of CCR5 with low-dose rapamycin enhances the antiviral activity of vicriviroc against both sensitive and drug-resistant HIV-1. Proc Natl Acad Sci U S A. 2008; 105:20476-81.

Gilliam BL, Heredia A, Devico A, Le N, Bamba D, Bryant JL, Pauza CD, Redfield RR.  Rapamycin reduces CCR5 mRNA levels in macaques: potential applications in HIV-1 prevention and treatment.  AIDS. 2007; 21:2108-10.

Heredia A, Gilliam B, Latinovic O, Le N, Bamba D, Devico A, Melikyan GB, Gallo RC, Redfield RR.  Rapamycin reduces CCR5 density levels on CD4 T cells, and this effect results in potentiation of enfuvirtide (T-20) against R5 strains of human immunodeficiency virus type 1 in vitro.  Antimicrob Agents Chemother. 2007; 51:2489-96.

Antivirals

Vu JR, Fouts T, Bobb K, Burns J, McDermott B, Israel DI, Godfrey K, DeVico A. An immunoglobulin fusion protein based on the gp120-CD4 receptor complex potently inhibits human immunodeficiency virus type 1 in vitro.  AIDS Res Hum Retroviruses. 2006.  22(6):477-90.

Zhang MY, Dimitrov DS. Novel approaches for identification of broadly cross-reactive HIV-1 neutralizing human monoclonal antibodies and improvement of their potency. Curr Pharm Des. 2007; 13:203-12.

Choudhry V, Zhang MY, Harris I, Sidorov IA, Vu B, Dimitrov AS, Fouts T, Dimitrov DS. Increased efficacy of HIV-1 neutralization by antibodies at low CCR5 surface concentration.  Biochem Biophys Res Commun. 2006; 348:1107-15.

Zhang MY, Shu Y, Rudolph D, Prabakaran P, Labrijn AF, Zwick MB, Lal RB, Dimitrov DS. Improved breadth and potency of an HIV-1-neutralizing human single-chain antibody by random mutagenesis and sequential antigen panning.  J Mol Biol. 2004; 335:209-19.

HIV Vaccine Immunogen

DeVico A, Fouts T, Lewis GK, Gallo RC, Godfrey K, Charurat M, Harris I, Galmin L, Pal R. Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens. Proc Natl Acad Sci U S A. 2007.  104(44):17477-82.

Fouts TR, Tuskan R, Godfrey K, Reitz M, Hone D, Lewis GK, DeVico AL. Expression and characterization of a single-chain polypeptide analogue of the human immunodeficiency virus type 1 gp120-CD4 receptor complex.  J Virol. 2000. 74(24):11427-36.

Genetic Adjuvants

Bagley KC, Shata MT, Onyabe DY, DeVico AL, Fouts TR, Lewis GK, Hone DM. Immunogenicity of DNA vaccines that direct the coincident expression of the 120 kDa glycoprotein of human immunodeficiency virus and the catalytic domain of cholera toxin. Vaccine. 2003. 21(23):3335-41.

Bagley KC, Abdelwahab SF, Tuskan RG, Fouts TR, Lewis GK. Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cAMP-dependent pathway. J Leukoc Biol. 2002. 72(5):962-9.

Bagley KC, Abdelwahab SF, Tuskan RG, Fouts TR, Lewis GK. Cholera toxin and heat-labile enterotoxin activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cyclic AMP-dependent pathway. Infect Immun. 2002. 70(10):5533-9.

 S.-Y. Chong, M. A. Egan, S. Megati, A. Masood, D. C. Montefiori, J. D. Boyer, J. Quiroz, M. Rosati, E. B. Schadeck, M. Sidhu, G. N. Pavlakis, D. B. Weiner, J. H. Eldridge, Z. R. Israel. A Comparative analysis of the adjuvant effects of plasmid IL-12 and IL-15 in SIVgag plasmid DNA immunized rhesus macaques. Vaccine 25:4967-4982 (2007).

E. B. Schadeck, M. Sidhu, M. A. Egan, S.-Y. Chong, P. Piacente, A. Masood, D. Garcia-Hand, S. Cappello, V. Roopchand, S. Megati, J. Quiroz, J. D. Boyer, B. K. Felber, G. N. Pavlakis, D. B. Weiner, J. H. Eldridge, Z. R. Israel. Plasmid encoded IL-12 functions as a DNA vaccine adjuvant and augments SIVgag-specific cell-mediated and humoral immune responses in Rhesus macaques. Vaccine, 24:4677-4687 (2006).

M. A. Kutzler, T. M. Robinson, M. A. Chattergoon, D. K. Choo, A. Y. Choo, P. Y. Choe, M. P. Ramanathan, R. Parkinson, S. Kudchodkar, Y. Tamura, M. Sidhu, V. Roopchand, J. J. Kim, G. N. Pavlakis, B. K. Felber, T. A. Waldman, J. D. Boyer, D. B. Weiner.  Co-immunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J. Immunol.,175:112 – 123, 2005

Boyer, JD., Robinson, TM., Kutzler, MA., Calarota, SA., Sidhu, MK., Muthumani, K., Lewis,M., Pavalakis, G., Felber, B., Weiner, DB. SIV DNA vaccine co-administered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques. J. Med. Primatology, 34:1-8 2005.

Chatergoon, M.A., Saulino, V., Shames, J., Stein, J., Montaner, L.J., and Weiner, D.B. co-immunization with plasmid IL-12 generates a strong T-cell memory response in mice. Vaccine  22:1744-1750, 2004.

Calarota, S.A., Otero, M., Hermanstayne, K., Lewis, M., Rosati, M., Felber, B.K., Pavlakis, G.N., Boyer, J.D., and Weiner, D.B.: Use of interleukin 15 to enhance interferon-gamma production by antigen-specific stimulated lymphocytes from rhesus macaques. J. Immunol. Methods, 279:55-67, 2003.

pDNA Vaccines

S. Megati, S. Cappello, V. Roopchand, D. Garcia-Hand, A. Masood, R. Xu, A. Luckay, S-Y. Chong, M. Rosati, S. Sackitey, D. B. Weiner, B. K. Felber, G. N. Pavlakis, Z. R. Israel, J. H. Eldridge, M. K. Sidhu and M. A. Egan. Modifying the HIV-1 env gp160 gene to improve pDNA vaccine-elicited cell mediated immune responses. Vaccine, 26:5083-5094 (2008).

M. A. Egan, Towards the Development of a Therapeutic Vaccine for the Treatment of HIV-1 Infection: Are We Closer Than Ever? Expert Rev. Vaccines, 6:289-291 (2007).

Luckay, M. K. Sidhu, R. Kjeken, S. Megati, S.-Yen Chong, V. Roopchand, D. Garcia-Hand, R. Abdullah, R. Braun, D. C. Montefiori, M. Rosati, B. K. Felber, G. N. Pavlakis, I. Mathiesen, Z. R. Israel, J. H. Eldridge and M. A. Egan. Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques. J. Virol, 81:5257-5269 (2007).

P. Spearman, S. Kalams, M. Elizaga, B. Metch, Y-L. Chiu, M. Allen, K. J. Weinhold, G. Ferrari, S. D. Parker, M. J. McElrath, S. E. Frey, J. D. Fuchs, M. C. Keefer, M. D. Lubeck, M. A. Egan, R. Braun, J. H. Eldridge, L. Corey, and the NIAID HIV Vaccine Trials Network.  Safety and Immunogenicity of a CTL Multiepitope Peptide Vaccine for HIV with or without GM-CSF in a Phase I Trial. Vaccine, submitted.

M. A. Egan, S. Megati, V. Roopchand, D. Garcia-Hand, A. Luckay, S.-Y. Chong, M. Rosati, B. K. Felber, G. N. Pavlakis, J. H. Eldridge, Z. R. Israel, M. K. Sidhu.  Rational design of a plasmid DNA vaccine capable of eliciting cell-mediated immune responses to multiple HIV antigens in mice. Vaccine, 24:4677-4687 (2006).

Muthumani K, Bagarazzi M, Conway D, Hwang DS, Manson K, Ciccarelli R, Israel Z, Montefiori DC, Ugen K, Miller N, Kim J, Boyer J and Weiner DB: A Gag-Pol/Env-Rev SIV239 DNA vaccine improves CD4 counts, and reduce viral loads after pathogenic intrarectal SIVmac251 challenge in Rhesus Macaques. Vaccine  21:629-637, 2003.

rVSV

M. A. Egan, S-Y. Chong, S. Megati  D. C. Montefiori, N. F. Rose, M. Sidhu, J. Quiroz, E. B. Schadeck, G. Pavlakis, D. B. Weiner, J. K. Rose, Z. R. Israel, S. A. Udem and J. H. Eldridge. Priming with Plasmid DNAs Expressing IL-12 and SIV Gag Protein Enhances the Immunogenicity and Efficacy of an Experimental AIDS Vaccine Based on Recombinant Vesicular Stomatitis Virus. AIDS Res. Human Retroviruses, 21:629-643 (2005).

Egan MA, Chong SY, Rose NF, Megati S, Lopez KJ, Schadeck EB, Johnson JE, Masood A, Piacente P, Druilhet RE, Barras PW, Hasselschwert DL, Reilly P, Mishkin EM, Montefiori DC, Lewis MG, Clarke DK, Hendry RM, Marx PA, Eldridge JH, Udem SA, Israel ZR, Rose JK.  Immunogenicity of attenuated vesicular stomatitis virus vectors expressing HIV type 1 Env and SIV Gag proteins: comparison of intranasal and intramuscular vaccination routes.  AIDS Res Hum Retroviruses. 2004; 20(9):989-1004.

Liao JB, Publicover J, Rose JK, DiMaio D.  Single-dose, therapeutic vaccination of mice with vesicular stomatitis virus expressing human papillomavirus type 16 E7 protein. Clin Vaccine Immunol. 2008, 15:817-24.

Schwartz JA, Buonocore L, Roberts A, Suguitan A Jr, Kobasa D, Kobinger G, Feldmann H, Subbarao K, Rose JK., Vesicular stomatitis virus vectors expressing avian influenza H5 HA induce cross-neutralizing antibodies and long-term protection.  Virology. 2007, 366:166-73.

Brandsma JL, Shylankevich M, Su Y, Roberts A, Rose JK, Zelterman D, Buonocore L.  Vesicular stomatitis virus-based therapeutic vaccination targeted to the E1, E2, E6, and E7 proteins of cottontail rabbit papillomavirus.  J Virol. 2007, 81:5749-58.

Brandsma JL, Shlyankevich M, Buonocore L, Roberts A, Becker SM, Rose JK.  Therapeutic efficacy of vesicular stomatitis virus-based E6 vaccination in rabbits. Vaccine. 2007, 25:751-62.

Roberts A, Reuter JD, Wilson JH, Baldwin S, Rose JK.  Complete protection from papillomavirus challenge after a single vaccination with a vesicular stomatitis virus vector expressing high levels of L1 protein. J Virol. 2004, 78:3196-9.

Reuter JD, Vivas-Gonzalez BE, Gomez D, Wilson JH, Brandsma JL, Greenstone HL, Rose JK, Roberts A.  Intranasal vaccination with a recombinant vesicular stomatitis virus expressing cottontail rabbit papillomavirus L1 protein provides complete protection against papillomavirus-induced disease.  J Virol. 2002, 76:8900-9. Erratum in: J Virol. 2003, 77:2799.

Haglund K, Leiner I, Kerksiek K, Buonocore L, Pamer E, Rose JK.  Robust recall and long-term memory T-cell responses induced by prime-boost regimens with heterologous live viral vectors expressing human immunodeficiency virus type 1 Gag and Env proteins.  J Virol. 2002, 76:7506-17.

Buonocore L, Blight KJ, Rice CM, Rose JK.  Characterization of vesicular stomatitis virus recombinants that express and incorporate high levels of hepatitis C virus glycoproteins.  J Virol. 2002, 76:6865-72.

Haglund K, Leiner I, Kerksiek K, Buonocore L, Pamer E, Rose JK. High-level primary CD8(+) T-cell response to human immunodeficiency virus type 1 gag and env generated by vaccination with recombinant vesicular stomatitis viruses. J Virol. 2002, 76:2730-8.

Rose NF, Marx PA, Luckay A, Nixon DF, Moretto WJ, Donahoe SM, Montefiori D, Roberts A, Buonocore L, Rose JK.  An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants. Cell. 2001, 106:539-49.

Rose NF, Roberts A, Buonocore L, Rose JK.  Glycoprotein exchange vectors based on vesicular stomatitis virus allow effective boosting and generation of neutralizing antibodies to a primary isolate of human immunodeficiency virus type 1. J Virol. 2000, 74:10903-10.

Roberts A, Buonocore L, Price R, Forman J, Rose JK.  Attenuated vesicular stomatitis viruses as vaccine vectors.   J Virol. 1999, 73:3723-32.

Haglund K, Forman J, Kräusslich HG, Rose JK.  Expression of human immunodeficiency virus type 1 Gag protein precursor and envelope proteins from a vesicular stomatitis virus recombinant: high-level production of virus-like particles containing HIV envelope. Virology. 2000, 268:112-21.

Lawson ND, Stillman EA, Whitt MA, Rose JK.  Recombinant vesicular stomatitis viruses from DNA. Proc Natl Acad Sci U S A. 1995, 92:4477-81. Erratum in: Proc Natl Acad Sci U S A,  1995, 92:9009.