Publications

Scholarly Journals--Published

  • Oludare Odumosu, Mavely Baez, Jessica Jutzy, Kimberly Payne, Nathan Wall, William Langridge, (2011). Suppression of Dendritic Cell Activation by Diabetes Autoantigens Linked to the Cholera Toxin B Subunit. Immunobiology, Apr:216 (4): 447-56.   (04/2011 - 11/2011)
  •  William  Langridge, Bela Denes and Istvan Fodor, (2010) Cholera toxin B subunit enhancement of vaccines for infectious and autoimmune diseases.Current Opinions in Investigational Drugs. Thompson Reuters Press77 Hatton Garden, London EC1N 8JS, UK. 11 (8):919-928.   (11/2010 - 11/2011)
  •  Denes B, Fodor I. and Langridge WHR. (2010). Autoantigens plus Interleukin 10 suppress diabetes autoimmunity. Diabets Technology and Therapeutics, 12:8.   (11/2010 - 11/2011)
  • Kahn S, JR Aspe, G Asumen, F Almaguel, O. Osumosu , S Acedevedo-Martinez, MN. DeLeon, WHR Langridge,and NR Wall.2009, Extracellular, cell permeable surivivin inhibits apoptosis while promoting proliferative and metastatic potential. British Journal of Cancer 7:100 (7):1073-86.   (11/2010 - 11/2011)
  •     Tae-Geum Kim , Nguyen-Xuan Huy , Mi-Young Kim , Dong-Keun Jeong, Yong-Suk Jang, Moon-Sik Yang, William H. R. Langridge  and Jin-Yong Lee  (2008), Expression and Immunogenicity of Cholera Toxin B Subunit-Porphyromonas gingivalis Fimbrial Antigen Fusion Proteins in E. coli, (accepted, August 08,  Molecular Biotechnology).   Immunogenicity of a Cholera Toxin B Subunit Porphyromonas gingivalis Fimbrial Antigen Fusion Protein Expressed in E. coli. Kim TG, Huy NX, Kim MY, Jeong DK, Jang YS, Yang MS, Langridge WH, Lee JY. Mol Biotechnol. 2008 Sep 20. [Epub ahead of print] PMID: 18807220  Abstract: The gram-negative anaerobic oral bacterium Porphyromonas gingivalis initiates periodontal disease through fimbrial attachment to saliva-coated oral surfaces. To study the effects of immunomodulation on enhancement of subunit vaccination, the expression in E. coli and immunogenicity of P. gingivalis fimbrial protein (FimA) linked to the C-terminus of the cholera toxin B subunit (CTB) were investigated. Complementary DNAs encoding the P. gingivalis 381 fimbrillin protein sequence FimA1 (amino acid residues 1–200) and FimA2 (amino acid residues 201– 337) were cloned into an E. coli expression vector downstream of a cDNA fragment encoding the immunostimulatory cholera toxin B subunit (CTB). CTB-FimA1 and CTB-FimA2 fusion proteins synthesized in E. coli BL21 (DE3) cells were purified under denaturing conditions by Ni2+-NTA affinity column chromatography. Renaturation of the CTB-FimA1 and CTB-FimA2 fusion proteins, permitted identification of CTB-FimA pentamers and restored CTB binding activity to GM1-ganglioside to provide a biologically active CTB-FimA fusion protein. Mice orally inoculated with purified CTB-FimA1 or CTB-FimA2 fusion proteins generated measurable FimA1 and FimA2 IgG antibody titers, while no serum fimbrial IgG antibodies were detected when mice were inoculated with FimA1 or FimA2 proteins alone.  Immunoblot analysis confirmed that sera from mice immunized with CTB linked to FimA1 or FimA2 contained antibodies specific for P. gingivalis fimbrial proteins. In addition, mice immunized with FimA2 or CTB-FimA2 generated measurable intestinal IgA titers indicating the presence of fimbrial antibody class switching. Further, mice orally immunized with CTB-FimA1 generated higher IgA antibody titers than mice inoculated with FimA1 alone.  The experimental data show that the immunostimulatory molecule CTB enhances B cell mediated immunity against linked P. gingivalis FimA fusion proteins in comparison to immunization with FimA protein alone. Thus, linkage of CTB to P. gingivalis fimbrial antigens can increase subunit vaccine immunogenicity to provide enhanced protection against periodontal disease. (08/2008 - 11/2008)
  • Choi NW, Estes MK, Langridge WH. " Ricin toxin B subunit enhancement of rotavirus NSP4 immunogenicity in mice.." Viral Immunology 19.1 (2006): 54-63. A 90-amino acid peptide from the simian rotavirus SA-11 nonstructural protein, NSP4 was linked to the N-terminus of the Ricinus communis A-B toxin B subunit protein (RTB) and synthesized in Escherichia coli. Recombinant RTB and the NSP4(90)::RTB fusion protein bound artificial receptor glycoprotein asialofetuin in an in vitro enzyme-linked immunosorbent assay (ELISA), demonstrating biological activity of the recombinant protein. Mice co-inoculated with purified recombinant RTB plus NSP4(90) peptide proteins or heat denatured NSP4(90)::RTB fusion protein generated higher titers of serum anti-NSP4(90) IgG antibodies than mice immunized with NSP4(90) peptide alone, indicating the presence of adjuvant functions for N-terminal linked RTB. Serum anti-NSP4(90) IgG titers were highest in mice immunized with native recombinant NSP4(90)::RTB fusion protein, confirming the immunostimulatory function of RTB. Results of experiments described here demonstrate the feasibility of using RTB mediated adjuvant functions for stimulation of the antigenicity of a rotavirus nonstructural protein. The ability of recombinant NSP4(90)::RTB fusion protein synthesized in E. coli to bind glycoprotein receptor molecules effectively indicates that protein linkage to the RTB N-terminus and synthesis of the recombinant NSP4(90)::RTB fusion protein in bacteria do not interfere with the immunostimulatory properties of the RTB subunit. (12/2006)
  • Dénes Béla , Yu Jie , Fodor Nadja , Takátsy Zsuzsanna , Fodor István , Langridge William H. R. . " Suppression of hyperglycemia in NOD mice after inoculation with recombinant vaccinia viruses. ." Journal of Molecular Biotechnology 34.3 (2006): 317-328. In autoimmune (type 1) diabetes, autoreactive lymphocytes destroy pancreatic beta-cells responsible for insulin synthesis. To assess the feasibility of gene therapy for type 1 diabetes, recombinant vaccinia virus (rVV) vectors were constructed expressing pancreatic islet autoantigens proinsulin (INS) and a 55-kDa immunogenic peptide from glutamic acid decarboxylase (GAD), and the immunomodulatory cytokine interleukin (IL)-10. To augment the beneficial effects of recombinant virus therapy, the INS and GAD genes were fused to the C terminus of the cholera toxin B subunit (CTB). Five-week-old non-obese diabetic (NOD) mice were injected once with rVV. Humoral antibody immune responses and hyperglycemia in the infected mice were analyzed. Only 20% of the mice inoculated with rVV expressing the CTB::INS fusion protein developed hyperglycemia, in comparison to 70% of the mice in the uninoculated animal group. Islets from pancreatic tissues isolated from euglycemic mice from this animal group showed no sign of inflammatory lymphocyte invasion. Inoculation with rVV producing CTB::GAD or IL-10 was somewhat less effective in reducing diabetes. Humoral antibody isotypes of hyperglycemic and euglycemic mice from all treated groups possessed similar IgG1/IgG2c antibody titer ratios from 19 to 32 wk after virus inoculation. In comparison with uninoculated mice, 11-wk-old NOD mice injected with virus expressing CTB::INS were delayed in diabetes onset by more than 4 wk. The experimental results demonstrate the feasibility of using rVV expressing CTB::INS fusion protein to generate significant protection and therapy against type 1 diabetes onset and progression. (11/2006) (link)
  • Choi NW, Estes MK, Langridge WH. . "Mucosal immunization with a ricin toxin B subunit-rotavirus NSP4 fusion protein stimulates a Th1 lymphocyte response. ." Journal of Biotechnology 121.2 (2006): 272-283. The castor-oil plant Ricinus communis A-B dimeric toxin B subunit (RTB) was genetically linked at its N-terminus with a 90 amino acid peptide from simian rotavirus SA-11 non-structural protein NSP4(90) and produced in Escherichia coli BL21 cells. Biologically active recombinant NSP4(90)-RTB fusion protein was shown to bind glycoprotein asialofetuin receptor molecules in an in vitro enzyme-linked immunosorbent assay (ELISA). Oral inoculation of the purified NSP4(90)-RTB ligand-antigen fusion protein delivered the chimeric protein to intestinal epidermal cells for mucosal immunization against rotavirus infection. Mice fed the NSP4(90)-RTB fusion protein generated higher humoral and intestinal antibody titers than mice inoculated with NSP4(90) alone. Titers of serum IgG2a antibodies were significantly higher than IgG1 titers suggesting a dominant Th1 lymphocyte immune response. ELISA measurement of cytokines secreted from splenocyte isolated from immunized mice confirmed NSP4(90)-RTB fusion protein stimulates a strong Th1 cell-mediated immune response. The experimental results demonstrate that the ricin toxin B subunit N-terminus can be used as a site for delivery of virus antigens to the gut associated lymphoid tissues for RTB-mediated immune stimulation of antiviral mucosal immune responses. (09/2006) (link)
  • Shin EA, Lee JY, Kim TG, Park YK, Langridge WH. . " Synthesis and assembly of an adjuvanted Porphyromonas gingivalis fimbrial antigen fusion protein in plants.." Protein Expression and Purification. 47.1 (2006): 99-109. The gram-negative anaerobic oral bacterium Porphyromonas gingivalis initiates periodontal disease by binding to saliva-coated oral surfaces. To assess whether edible plants can synthesize biologically active P. gingivalis fimbrial antigen, for application as an oral vaccine, a cDNA fragment encoding the C-terminal binding portion of P. gingivalis fimbrial protein (FimA), was cloned into a plant expression vector immediately downstream of a cDNA fragment encoding the cholera toxin B subunit (CTB). The chimeric plasmid was transferred into potato (Solanum tuberosum) cells and the ctb-fimA cDNA fragment detected in transformed leaf genomic DNA by PCR amplification methods. A novel protein band of 21 kDa was detected in transformed potato tuber extracts by immunoblot analysis. Oligomeric CTB-FimA (266-337) fusion protein was identified in the extracts through the binding of anti-CTX and anti-native fimbriae antibodies. The pentameric structure of CTB-FimA fusion protein was confirmed by ELISA measurements of GM1 ganglioside receptor binding. Quantification of the CTB-FimA fusion protein by ELISA indicated that the chimeric protein made up about 0.33% of total soluble tuber protein. The biosynthesis of immunologically detectable CTB-FimA fusion proteins and the assembly of fusion protein monomers into biologically active pentamers in transformed potato tuber tissues demonstrate the feasibility of synthesizing adjuvanted fimbrial protein in edible plants for development of adjuvanted mucosal vaccines against P. gingivalis generated periodontal disease. (07/2006) (link)
  • Carter JE 3rd, Yu J, Choi NW, Hough J, Henderson D, He D, Langridge WH. . "Bacterial and plant enterotoxin B subunit-autoantigen fusion proteins suppress diabetes insulitis. ." Molecular Biotechnology 32.1 (2006): 1-15. Several bacterial and plant enterotoxin B subunit-islet autoantigen fusion proteins were compared for their ability to serve as islet autoantigen carriers and adjuvants for reduction of pancreatic islet inflammation associated with type 1 diabetes. The cholera toxin B subunit (CTB), the heat-labile toxin B subunit from enterotoxigenic Escherichia coli (LTB), the Shigella toxin B subunit (STB), and the plant toxin ricin B subunit (RTB) were genetically linked to the islet autoantigens proinsulin (INS) and glutamic acid decarboxylase (GAD). The adjuvant-autoantigen gene fusions were transferred to a bacterial expression vector and the corresponding fusion proteins synthesized in E. coli. The purified adjuvant-autoantigen proteins were fed to 5-wk-old nonobese diabetic (NOD) mice once a week for 4 wk. Histological examination of pancreatic islets isolated from inoculated mice showed significant levels of insulitis reduction in comparison with uninoculated mice. The ratio of serum anti-INS and anti-GAD IgG2c to IgG1 antibody isotype titers increased in all ligand-autoantigen inoculated animal groups, suggesting an increase in effector Th2 lymphocytes in B subunit-mediated insulitis suppression. The results of these experiments indicate that bacterial and plant enterotoxin B subunit ligand-autoantigens enhance insulitis reduction in NOD mice. This research prompts further exploration of a multiadjuvant/autoantigen co-delivery strategy that may facilitate type 1 diabetes prevention and suppression in animals and humans. (07/2006) (link)
  • Kim TG, Galloway DR, Langridge WH.. "Synthesis and assembly of anthrax lethal factor-cholera toxin B-subunit fusion protein in transgenic potato.." Molecular Biotechnology 28 .(3) (2005): 175-183. A DNA encoding the 27-kDa domain I of anthrax lethal factor protein (LF), was linked to the carboxyl terminus of the cholera toxin B-subunit (CTB-LF). The CTB-LF fusion gene was transferred into Solanum tuberosum cells by Agrobacterium tumefaciens-mediated in vivo transformation methods and antibiotic-resistant plants were regenerated. The CTB-LF fusion gene was detected in transformed potato leaf genomic DNA by polymerase chain reaction (PCR)-mediated DNA amplification. Immunoblot analysis with anti-CTB and anti-LF primary antibodies verified the synthesis and assembly of biologically active CTB-LF fusion protein oligomers in transformed plant tuber tissues. Furthermore, the binding of CTB-LF fusion protein pentamers to intestinal epithelial cell membrane receptors measured by GM1-ganglioside enzyme-linked immunosorbent assay (GM1-ELISA) indicated that the CTB-LF fusion protein made up approx 0.002% of the total soluble tuber protein. Synthesis of CTB-LF monomers and their assembly into biologically active CTB-LF fusion protein pentamers in potato tuber tissues demonstrates the feasibility of using edible plants for production and delivery of adjuvanted LF protein for CTB-mediated immunostimulation of mucosal immune responses against anthrax toxin. (11/2005) (link)
  • Lee JY, Yu J, Henderson D, Langridge WH.. "Plant-synthesized E. coli CFA/I fimbrial protein protects Caco-2 cells from bacterial attachment.." Vaccine 23.(2) (2005): 222 -231. A DNA fragment encoding the cholera toxin A2 subunit (CTA2) linked to the enterotoxigenic Escherichia coli (ETEC) colony forming fimbrial antigen CFA/I was inserted into a plant expression vector containing the cholera toxin B subunit (CTB) fused to the rotavirus enterotoxin 22 amino acid epitope NSP422. Anti-CFA/I antibodies recognized a single band of approximately 72-kDa in transformed potato tuber tissue consistent with CFA/I-CTA2 and CTB-NSP4 fusion protein assembly into a cholera holotoxin-like structure. Enzyme-linked immunosorbent assay (GM1 ELISA) indicated that the CFA/I-CTA2 fusion protein bound specific GM1 ganglioside membrane receptors and made up approximately 0.002% of the total soluble tuber protein. Oral immunization of BALB/c mice with transformed tuber tissues generated anti-CFA/I serum and intestinal IgG and IgA secretory antibodies. Attachment of ETEC H10407 to enterocyte-like Caco-2 human colon carcinoma cells incubated with antiserum from immunized mice was reduced by 15% in comparison with Caco-2 cells incubated with serum from unimmunized mice. Immunogold staining of bacterial preparations revealed deposition of gold particles on E. coli H10407 fimbria incubated with immune serum but not on fimbria treated with sera from unimmunized mice demonstrating the specificity of antibodies in the immune serum for binding to CFA/I protein containing fimbria. The protection against toxic E. coli binding to Caco-2 cells generated by antisera from mice immunized with plant-synthesized CFA/I antigen demonstrates the feasibility of plant-based multi-component vaccine protection against enterotoxigenic E. coli, rotavirus and cholera, three enteric diseases that together exert the highest levels of child morbidity and mortality in economically emerging countries (11/2005) (link)
  • Denes B, Krausova V, Fodor N, Timiryasova T, Henderson D, Hough J, Yu J, Fodor I, Langridge WH. . "Protection of NOD mice from type 1 diabetes after oral inoculation with vaccinia viruses expressing adjuvanted islet autoantigens.." Journal of Immunotherapy 28.(5) (2005): 438-448. Oral administration of autoantigens and allergens can delay or suppress clinical disease in experimental autoimmune and allergic disorders. However, repeated feeding of large amounts of the tolerogens is required over long periods and is only partially effective in animals systemically sensitized to the ingested antigen. Enhanced suppression of type 1 autoimmune diabetes insulitis and hyperglycemia was demonstrated in both naive and immune animals following oral inoculation with plant-based antigens coupled to the cholera toxin B subunit (CTB). Thus, plant-synthesized antigens linked to the CTB adjuvant, can enhance suppression of inflammatory TH1 lymphocyte-mediated autoreactivity in both naive and immune animals. To stimulate adjuvant-autoantigen fusion protein biosynthesis in the gut mucosae, the authors evaluated oral inoculation of juvenile non-obese diabetic (NOD) mice with recombinant vaccinia virus (rVV) expressing fusion genes encoding CTB linked to the pancreatic islet autoantigens proinsulin (INS) and a 55-kDa C-terminal peptide from glutamate decarboxylase (GAD55). Hyperglycemia in both rVV-CTB:: INS and rVV-CTB:: GAD inoculated mice was substantially reduced in comparison with the uninoculated mouse control. Oral inoculation with rVV carrying the CTB::INS fusion gene generated a significant reduction in insulitis. An increase in IgG1 in comparison with IgG2c antibody isotype titers in rVV-CTB::INS infected mice suggested possible activation of autoantigen specific Th2 lymphocytes. The experimental results demonstrate feasibility of using vaccinia virus oral delivery of adjuvanted autoantigens to the mucosae of prediabetic mice for suppression and therapy of type 1 autoimmune diabetes. (09/2005) (link)
  • Kim TG, Ruprecht R, Langridge WH. . "SIVmac Gag p27 capsid protein gene expression in potato.." Protein Expression and Purification 36.(2) (2005): 312 -317. A cDNA encoding the Simian immunodeficiency virus type (SIV(mac)) Gag capsid protein was introduced into Solanum tuberosum cells by Agrobacterium tumefaciens-mediated transformation methods. The gag gene was detected in the genomic DNA of transformed leaf tissues by PCR DNA amplification. Immunoblot analysis of transformed potato plant extracts with anti-Gag monoclonal antibody showed that biologically active Gag protein was synthesized in transformed tuber tissues. Based on ELISA results, recombinant Gag protein made up 0.006-0.014% of total soluble tuber protein. The synthesis of SIV Gag in transformed potato tubers opens the way for development of Gag-based edible plant vaccines for protection against SIV and potentially HIV-1 infection. (08/2005) (link)
  • Kim TG, Gruber A, Ruprecht RM, Langridge WH. . "Synthesis and assembly of SIVmac Gag p27 capsid protein cholera toxin B subunit fusion protein in transgenic potato.." Molecular Biotechnology 28.(1) (2005): 33-40. A deoxyribonucleic acid (DNA) fragment encoding the cholera toxin B subunit (CTB) was linked 5' to the simian immunodeficiency virus (SIVmac) Gag p27 capsid gene (CTB-Gag). The fusion gene was transferred into Solanum tuberosum cells by Agrobacterium tumefaciens-mediated transformation methods and transformed plants regenerated. The CTB-Gag gene fusion was detected in transformed potato leaf genomic DNA by polymerase chain reaction-mediated DNA amplification. The results of immunoblot analysis with anti-CTB and anti-Gag antibodies verified the synthesis of biologically active CTB-Gag fusion protein in transformed leaf and tuber tissues. Synthesis and assembly of the CTB-Gag fusion protein into oligomeric structures of pentamer size was confirmed by GM1-ganglioside-enzyme-linked immunosorbent assay (GM1-ELISA) of transformed potato tuber tissue extracts. The binding of CTB-Gag fusion protein oligomers to intestinal epithelial cell membrane receptors quantified by GM1-ELISA showed that CTB-Gag fusion protein made up approx 0.016-0.022% of the total soluble tuber protein. The synthesis of CTB-Gag monomers and their assembly into biologically active CTB-Gag fusion protein oligomers in potato tuber tissues provides the opportunity for employment of the carrier and adjuvant properties of CTB for the development of edible plant-based subunit mucosal vaccines for enhanced mucosal immunity against SIV in macaques. (07/2005) (link)
  • Kim, T-G, J Yu, J Hough, D Henderson, and W.H.R Langridge,. "An HIV-1 Tat-autoantigen fusion protein suppresses diabetes insulitis in NOD mice. ." Molecular Biotechnology 30.3 (2005): 221-229. (01/2005)
  • Choi, N-W, Estes, M K.,and Langridge,WHR. " Synthesis and Assembly of a Cholera Toxin B Subunit-Rotavirus VP7 Fusion Protein in Transgenic Potato." Molecular Biotechnology 31.3 (2005): 193-202. (01/2005)
  • Choi, N-W, Estes, M K.,and Langridge, W.H.R. . "Oral immunization with a Shigatoxin B subunit rotavirus NSP4 fusion protein protects mice against gastroenteritis.." Vaccine 23.44 (2005): 5168-5176. (01/2005)
  • Kim, T-G, Ruprecht, R. and Langridge, W.H.R. "Synthesis and assembly of a cholera toxin B subunit SHIV Tat fusion protein in transgenic potato." Protein Expression and Purification 36. (2004): 312-317. (07/2004) (link)
  • Kim, T-G, Gruber, A. and Langridge, W.H.R. "HIV-1 gp120 V3 cholera toxin B subunit fusion gene expression in transgenic potato." Protein Expression and Purification 37. (2004): 196-202. (07/2004) (link)
  • Kim, T-G and Langridge, W.H.R.. "Synthesis of an HIV-1 Tat transduction domain-rotavirus enterotoxin fusion protein in transgenic potato." Plant Cell Reports, (6). (2004): 382-387. (07/2004)
  • Kim, T-G, Befus, N and Langridge, W.H.R. "Co-immunization with an HIV-1 Tat transduction peptide-rotavirus enterotoxin fusion protein stimulates a Th1 mucosal immune response in mice." Vaccine 22. (2004): 431-438. (07/2004) (link)
  • Kim, T-G, Befus, N and Langridge, W.H.R.. "Co-immunization with an HIV-1 Tat transduction peptide-rotavirus enterotoxin fusion protein stimulates a Th1 mucosal immune response in mice.." Vaccine 22.3-4 (2004): 431-438. (01/2004)
  • Kim, T-G and Langridge, W.H.R.. "Synthesis of an HIV-1 Tat transduction domain-rotavirus enterotoxin fusion protein in transgenic potato.." Plant Cell Reports 6. (2004): 382-387. (01/2004)
  • Kim, T-G, Ruprecht, R. and Langridge, W.H.R.. "SIVMAC Gag p27 capsid protein gene expression in potato.." Protein Expression and Purification 36. (2004): 312-317. (01/2004)
  • Kim, T-G, Gruber, A. and Langridge, W.H.R.. "HIV-1 gp120 V3 cholera toxin B subunit fusion gene expression in transgenic potato.." Protein Expression and Purification 37. (2004): 196-202. (01/2004)
  • Lee, J-Y., Yu, J., Henderson, D. and Langridge, W.H.R.. "CFA/I fimbrial antigen synthesized in potato blocks enterotoxigenic E. coli binding to Caco 2 cells.." Vaccine 23. (2004): 222-231. (01/2004)
  • Kim, Tae-Geum, Galloway, D.R. and Langridge, W. H. R.. "Synthesis and assembly of anthrax lethal factor cholera toxin B subunit fusion protein in transgenic potato.." Molecular Biotechnology 28.3 (2004): 175-183. (01/2004)
  • Kim, T-G, Gruber, A. and Langridge, W.H.R.. "Synthesis and assembly of an SIVMAC Gag p27capsid protein - cholera toxin B subunit fusion protein in transgenic potato.." Molecular Biotechnology 28.1 (2004): 33-40. (01/2004)
  • Kim, T-G, Ruprecht, R. and Langridge, W.H.R.. "Synthesis and assembly of a cholera toxin B subunit SHIV Tat fusion protein in transgenic potato.." Protein Expression and Purification 36. (2004): 312-317. (01/2004)
  • Kim, T-G., Choi, N-W. and Langridge, W.H.R.. "Expression of cholera toxin B subunit-rotavirus enterotoxin fusion gene in transgenic potato.." Transgenics 4.2 (2003): 88-. (01/2003)
  • Kim, T-G. and Langridge, W.H.R.. " Assembly of cholera toxin B subunit-full length rotavirus NSP4 fusion protein oligomers in transgenic potato.." Plant Cell Reports, 21. (2003): 884-890. (01/2003)
  • Umphress, S., Timiryasova, T.M., Arakawa, T., Hilliker, S., Fodor, I. and Langridge W.H.R.. " Vaccinia virus mediated expression of human APC induces apoptosis in colon cancer cells.." Transgenics 4. (2003): 19-33. (01/2003)
  • Snowden, S.L. and Langridge, W.H.R., . "Plant-based mucosal immunization. ." Biotechnology and Genetic Engineering Reviews, 20. (2003): 1-36. (01/2003)
  • Carter, J.E. and Langridge, W.H.R.. "Transgenic Plant Vaccines,." 2003 Yearbook of Science and Technology, . (2003): 430-433. (01/2003)
  • Yu, J. and Langridge, W.H.R., . "Expression of rotavirus capsid protein VP6 in transgenic potato and its oral immunogenicity in mice.." Transgenic Research 12.2 (2003): 163-169. (01/2003)
  • Carter, J. and Langridge, W.H.R.. "Plant-based vaccines for protection against infectious and autoimmune diseases.." Critical Reviews in Plant Sciences 21.2 (2002): 93-109. (01/2002)
  • Yu, J. and Langridge, W.H.R., . "A plant-based multicomponent vaccine protects mice from enteric diseases." Nature Biotechnology 19. (2001): 548-552. (01/2001)
  • Sovyanhadi, Y., Arakawa, T. and Langridge, W.H.R., . "Human β casein gene expression in transgenic tomato plants." Transgenics 3.2-4 (2001): 199-206. (01/2001)
  • Chong, K.X.D. and Langridge, W.H.R.. "Synthesis and assembly of cholera holotoxin in potato plants.." Transgenics 3.3-4 (2001): 167-174. (01/2001)
  • Arakawa, T., Yu, J. and Langridge, W.H.R.. "Synthesis of a cholera toxin B subunit- rotavirus NSP4 fusion protein in potato.." Plant Cell Reports 20.4 (2001): 343-348. (01/2001)
  • Yu, J., Arakawa, T. and Langridge,W.H.R.. "Assembly of cholera toxin-antigen fusion proteins in transgenic potato.." Transgenics 3.3-4 (2001): 153-162. (01/2001)
  • Langridge, W.H.R., . "Edible vaccines.." Scientific American. 283.3 (2000): 48-53. (01/2000)
  • Yu, J. and Langridge, W.H.R.. "Novel approaches to oral vaccines - delivery of antigens by edible plants.." Current Infectious Disease Reports 2.1 (2000): 73-77. (01/2000)
  • Befus, N. and Langridge, W.H.R. "Plant-based cholera toxin B subunit-insulin/GAD fusion proteins suppress the development of autoimmune diabetes.." Bundesgesundheitsblatt 43.2 (2000): 116-120. (01/2000)
  • Chong, D.X.K. and Langridge, W.H.R.. "Expression of full length bioactive human lactoferrin in transgenic potato plants.." Transgenic Research 9.1 (2000): 71-78. (01/2000)
  • Arakawa, T., Yu J., and Langridge W.H.R.. "Food plant delivered cholera toxin B subunit for vaccination and immunotolerization.." Adv. Exp. Med. Biol, 464. (1999): 161-178. (01/1999)
  • Timiryasova, T.M., Li, J.,Chen,B., Chong, D., Langridge, W.H.R., Gridley,D.S. and Fodor,I.. "Antitumor effect of vaccinia in a glioma model.." Oncology Research 11. (1999): 133-144. (01/1999)
  • Arakawa, T., Chong, D.K.X., Yu, J., Hough, J., Engen, P.C., Elliott, J.F. and Langridge W.H.R.,. "Suppression of autoimmune diabetes by a plant-delivered cholera toxin B subunit-human glutamate decarboxylase fusion protein,." Transgenics 3. (1999): 51-60. (01/1999)
  • Langridge, W.H.R. and Arakawa, T.. "Plant-based vaccines for immunotolerization, mucosal immunology update,." In: Plant Vaccines, 7.1 (1999): 6-7. (01/1999)
  • Fatyol, K. K. Illes, T. Praznovszky, W.H.R.Langridge, G. Hadlaczky and A.A Szalay,. "Molecular characterization of a stably transfected Bombyx mori cell line: Identification of alternative transcriptional initiation sites of the A3 cytoplasmic actin gene.." Molec.Gen.Genetics 260. (1998): 1-8. (01/1998)
  • Arakawa T, Chong, D.K.X., Slattery C.W. and Langridge W.H.R.,. "Improvements in Human Health Through the Production of Human Milk Proteins in Transgenic Food Plants." In Chemicals via Higher Plant Bioengineering, Chapter 12. (1998): 149-160. (01/1998)
  • Arakawa, T, Jie Yu., and Langridge W.H.R.,(. "Food Plant-delivered Cholera Toxin B Subunit for Vaccination and Immunotolerization,." In Chemicals via Higher Plant Bioengineering, Chapter 13. (1998): 161-178. (01/1998)
  • Arakawa, T. and Langridge,W.H.R., . "Transgenic Plant-based Vaccines." Experimental Medicine 16. (1998): 2224-2226. (01/1998)
  • McCracken, J.D., Godil, A., Murray, E.D., Kantoci, D., Gridley, D.S., Langridge, W.H.R,. Pant, K.D. and Wechter, W.J.. "R-flurbiprofen Suppresses LS174T Xenograft Growth In the Nude Rat.." Proc. Am. Assoc. Cancer Res., 39. (1998): 314-. (01/1998)
  • Timiryasova, T., Li, J., Chong, D.K.X., Langridge, W.H.R., Gridley, D.S. and Fodor, I.. "Vaccinia Virus Mediated in Vitro and ex Vivo Delivery of the P53 Gene into Glioma Cells for Therapy of Glial Tumors.." Cancer Gene Therapy 4.6 (1998): S20-. (01/1998)
  • Arakawa, T., Chong, D.K.X., Yu, J., Hough, J.,Engen, P.C., Elliott, J.F. and Langridge W.H.R., . "A Plant-based Cholera Toxin B Subunit-insulin Fusion Protein Protects Against Development of Autoimmune Diabetes." Nature Biotechnology 16. (1998): 934-938. (01/1998)
  • Arakawa, T. and Langridge, W.H.R., . "Plants Are Not Just Passive Creatures!, ." Nature Medicine, News and Views 4.5 (1998): 550-551. (01/1998)
  • Arakawa, T., Chong, D.K.X. and Langridge W.H.R.,. "Efficacy of a Food Plant-Based Oral Cholera Toxin B Subunit Vaccine." Nature Biotechnology 16. (1998): 292-297. (01/1998)
  • Arakawa, T., Chong, D.K.X., Slattery, C. Hilliker, S. and Langridge, W.H.R.,. " Food plant-derived human milk proteins for improved nutrition.,." AgBiotech News and Information. 10.4 (1998): 103N-110N. (01/1998)
  • Langridge, W.H.R. and Szalay, A.A., . "Arabidopsis Protocols: Bacterial and Coelenterate Luciferases as Reporter Genes in Plant Cells,." Methods in Molecular Biology, 82. (1998): 385-396. (01/1998)
  • Arakawa, T., Chong, D. K. X., Merritt, J.L. and Langridge, W.H.R., . "Expression of Cholera Toxin B Subunit Oligomers in Transgenic Potato Plants.." Transgenic Research, 6. (1997): 403-413. (01/1997)
  • Chong D., Roberts, W., Bagi G., Illes., Arakawa T., Slattery C., and Langridge W.H.R.,. "Expression of the human milk protein β casein in transgenic potato." Transgenic Research, 6. (1997): 289-296. (01/1997)
  • Langridge W.H.R., Krausova V.I., Szalay A.A. and Fodor I.,. "Detection of gene expression in insect cells and larvae by low light image analysis.." Journal of Virological Methods 61. (1996): 151-156. (01/1996)
  • Mayerhofer R., Langridge W.H.R., Cormier M.J. and Szalay A.A.. "Expression of recombinant Renilla Luciferase in transgenic plants results in high levels of light emission ." The Plant Journal, 7. (1995): 1031-1038. (01/1995)
  • Meyerhofer R., Wang G., Hua D., Escher, A., Illes K., Langridge, WHR and Szalay AA*.. "Visualization of light emission from different luciferases in transgenic organisms, bioluminescence and chemiluninescence, fundamentals and applied aspects, Part 8, Imaging of Luminescence. ." Proceedings, 8th International Symposium on Bioluminescence and Chemiluminescence, . (1994): 607-612. (01/1994)
  • Langridge W.H.R., Escher A.P., Wang G., Ayre B., Fodor I. and Szalay A.A.. "Low Light Image Analysis of Transgenic Organisms Using Bacterial Luciferase as a Marker,." Journal of Bioluminescence and Chemiluminescence, 9. (1994): 185-200. (01/1994)
  • Garcia Lloret, M.I., Guilbert, L.J., Langridge, W.H.R. and A.A.Szalay. "Intermediates by Placental Trophoblasts, Production of Reactive Oxygen ." Bioluminescence and Chemiluminescence, Current Status, . (1993): 451-455. (01/1993)
  • Wang, G., Mayerhofer, R., Langridge, W.H.R. and Szalay, A.A.. "Expression of a Bacterial Luciferase Marker Gene in Bacillus Species, ." Bioluminescence and Chemiluminescence, Current Status, . (1993): 227-231. (01/1993)
  • Langridge, W.H.R., Baga, M., Ayer, W,. Koorneef, M and Szalay, A.A.. "Use of an Auxin Stimulated Promoter-Luciferase Gene Fusion to Monitor Hormone Stimulated Gene Expression in Transgenic Plants,." Bioluminescence and Chemiluminescence, Current Status, . (1993): 222-226. (01/1993)
  • Langridge, W.H.R., Jiang, C., Wang, G., Giacoman, L., Dale, P., Baga, M., Fodor, I. and Szalay, A.A.. "Use of a Luciferase Marker Gene System to Monitor Gene expression in Bacteria, Plant and Virus Infected Animal Cells ." Bioluminescence and Chemiluminescence, Current Status, . (1993): 217-221. (01/1993)
  • Jiang, C., Langridge, W.H.R. and Szalay, A.A. . "Isolation of Plant Promoters by Insertional Activation of a Promoterless Bacterial Luciferase Gene,." Bioluminescence and Chemiluminescence, Current Status, Szalay, A.A., Stanley, P.E. and Kricka, L.J. eds., John Wiley and Sons, Chichester, . (1993): 212-216. (01/1993)
  • Alton, G., Langridge, W.H.R. and Szalay, A.A.. "Evaluation of a versatile imaging camera apparatus for chemiluminescent ELISA and monitoring bacterial bioluminescence.." Bioluminescence and Chemiluminescence, Current Status . (1993): 3-7. (01/1993)
  • Tamas, I.A., Langridge, W.H.R., Abel, S.D., Crawford, S.W., Randall, J.D., Schell, J. and Szalay A.A.(. "Hormonal control of apical dominance. Studies in tobacco transformed with bacterial luciferase and Agrobacterium rol genes.." In: Plant Growth Substances, . (1992): 418-430. (01/1992)
  • Baga, M., Langridge, W.H.R. and Szalay, A.A. . " Functional analysis of the plant hormone regulated dual mas promoter region.." In: Plant Growth Substances, . (1992): 759-764. (01/1992)
  • Jiang,C., Langridge, W.H.R. and Szalay, A.A. . "Identification of Plant Genes in vivo by tagging with T-DNA border linked luciferase genes followed by inverse polymerase chain reaction amplification.." Plant Molecular Biology Reporter, 10.4 (1992): 354-361. (01/1992)
  • Langridge, W.H.R., Escher, A., and Szalay, A.A.. "Use of the bacterial luciferase reporter gene system to monitor gene expression in bacteria, yeast and plant cells throughout development.." Technique, J. Meth. inCell and Mol. Biol . 3.3 (1991): 91-. (01/1991)
  • Langridge, W.H.R., Escher, A., Koncz, C., Schell, J., and Szalay, A.A.. "Bacterial luciferase genes: A light emitting reporter system for in vivo measurement of gene expression.." Technique, J. Meth. in Cell and Mol. Biol., 3. (1991): 83-. (01/1991)
  • Koncz, C., Langridge, W.H.R., Olsson, O., Schell, J. and Szalay, A.A.. "Bacterial and firefly luciferase genes in transgenic plants: advantages and disadvantages of a reporter gene.." In: "Foreign genes in their transgenic plant environment" Kahl (ed). Developmental Genetics 11. (1990): 224-232. (01/1990)
  • Escher, A.P., O'Kane, D., Lee, J., Langridge, W.H.R., and Szalay, A.A.. "Construction of a novel functional bacterial luciferase by gene fusion and its use as a gene marker in low light video image analysis." In: New Methods in Microscopy and Low Light Imaging. 1161. (1989): 230-234. (01/1989)
  • Langridge, W.H.R., Escher, A., Baga, M., O'Kane, D., Wampler, J., Koncz, C., Schell, J., and Szalay A.A.. "Use of low light image microscopy to monitor genetically engineered bacterial luciferase gene expression in living cells and gene activation throughout the development of a transgenic organism.." New Methods in Microscopy and Low Light Imaging 1161. (1989): 216-229. (01/1989)
  • Langridge, W.H.R., Fitzgerald, K.J., Koncz, C., Schell, J., and Szalay, A.A.. "The dual promoter of A. tumefaciens mannopine synthase genes is regulated by plant growth hormones.." Proc. Natl. Acad. Sci., U.S.A 86. (1989): 3219-3223. (01/1989)
  • Langridge, W.H.R., Li, B.J., and Szalay, A.A.. "Uptake of DNA and RNA into cells mediated by electroporation.." Methods in Enzymology: Recombinant DNA. Part D, Section 1 153. (1987): 336-350. (01/1987)
  • Koncz, C., Olsson, O., Langridge, W.H.R., Schell, J., and Szalay, A.A.. "Expression and functional assembly of bacterial luciferase in plants.." Proc. Natl. Acad. Sci., U.S.A. 84. (1987): 131-135. (01/1987)
  • Langridge, W.H.R., Li, B.J., and Szalay, A.A. . "Electric field mediated transfer of nucleic acids into carrot protoplasts. ." In: Genetic Manipulation in Plant Breeding. Proceedings Eucarpia International Symposium on Genetic Manipulation in Plant Breeding . (1986): 785-802. (01/1986)
  • Nishiguchi, M., Langridge, W.H.R., Szalay, A.A., and Zaitlin, M. . "Electroporation mediated infection of tobacco leaf protoplasts with tobacco mosaic virus RNA and cucumber mosaic virus RNA.." Plant Cell Reports 5. (1985): 57-60. (01/1985)
  • Li, B.J., Langridge, W.H.R., and Szalay, A.A. . "Electric field mediated stable transformation of carrot protoplasts with naked DNA.." Scientia Sinica, Series B . (1985): -. (01/1985)
  • Li, B.J., Langridge, W.H.R., and Szalay, A.A.. "Somatic embryogenesis and plantlet regeneration in the soybean Glycine max.." Plant Cell Reports 4. (1985): 344-347. (01/1985)
  • Langridge, W.H.R., Li, B.J., and Szalay, A.A.. "Electric field mediated stable transformation of carrot protoplasts with naked DNA.." Plant Cell Reports 4. (1985): 35-. (01/1985)
  • Jaeger, B. and Langridge, W.H.R.. "Infection of Locusta migratoria with entomopoxviruses from Arphia conspersa and Melanoplus sanguinipes grasshoppers.." Journal of Invertebrate Pathology 43. (1984): 374-382. (01/1984)
  • Langridge, W.H.R.. "Detection of DNA base sequence homology between Entomopoxviruses Isolated from Lepidoptera and Orthoptera." Journal of Invertebrate Pathology 43. (1984): 41-46. (01/1984)
  • Compton, J.L., Krauss, M.R., Langridge, W.H.R., and Szalay, A.A.. "The expression of plant DNA sequences in yeast." Journal of Cellular Biochemistry 1215. (1983): 269-. (01/1983)
  • Langridge, W.H.R.. "Characterization of a cytoplasmic polyhedrosis virus from ." Journal of Invertebrate Pathology 42. (1983): 259-263. (01/1983)
  • Langridge, W.H.R.. "Detection of Amsacta moorei entomopoxvirus and vaccinia virus proteins in cell cultures restrictive for poxvirus multiplication.." Journal of Invertebrate Pathology 42. (1983): 77-82. (01/1983)
  • Langridge, W.H.R., Oma, E., and Henry, J.E.. "Characterization of Entomopox virus DNA from Melanoplus sanguinipes, Arphia conspirsa and Phoetaliotes nebrascensis (Orthoptera)." Journal of Invertebrate Pathology 42. (1983): 327-333. (01/1983)
  • Langridge, W.H.R.. "Partial characterization of DNA from five entomopoxviruses.." Journal of Invertebrate Pathology, 42. (1983): 369-375. (01/1983)
  • Langridge, W.H.R.. "Virus DNA replication and protein synthesis in Amsacta entomopoxvirus-infected Estigmene acrea cells.." Journal of Invertebrate Pathology 41. (1983): 34-39. (01/1983)
  • Cattano, S.P. and Langridge, W.H.R.. "Characterization of the DNA from a granulosis virus of Estigemene acrea (Lepidoptera).." Virology 119. (1982): 199-203. (01/1982)
  • Langridge, W.H.R. and Roberts, D.W.. "Structural proteins of Amsacta moorei, Euxoa auxiliaris and Melanoplus sanguinipes entomopoxvirus.." Journal of Invertebrate Pathology 39. (1982): 346-353. (01/1982)
  • Langridge, W.H.R.. "Biochemical properties of a persistent nonoccluded baculovirus isolated from Heliothis zea cells.." Virology 112. (1981): 770-774. (01/1981)
  • Langridge, W.H.R. and Balter, K.. "Protease activity associated with the capsule protein of Estigmene acrea granulosis virus.." Virology 114. (1981): 595-600. (01/1981)
  • Langridge, W.H.R. and Greenberg, J.F.. "Detection of entomopoxvirus proteins in insect cell culture by enzyme-linked immunosorbent assay (ELISA).." Journal of General Virology 57. (1981): 215-219. (01/1981)
  • Wood, H.A., Hughes, P.R., Johnston, L.B., and Langridge, W.H.R.. "Increased virulence of Autographa californica nuclear polyhedrosis virus by mutagenesis.." Journal of Invertebrate Pathology 38. (1981): 235-241. (01/1981)
  • Langridge, W.H.R., Granados, R.R., and Greenberg, J.F.. "Detection of Autographa californica and Heliothis zea baculovirus proteins by enzyme-linked immunosorbent assay (ELISA).." Journal of Invertebrate Pathology 38. (1981): 242-250. (1981) , 38:242-250. (01/1981)
  • Langridge, W.H.R., Granados, R.R., and Greenberg, J.F. . "Detection of baculovirus protein in cell culture and insect larvae by enzyme-linked immunosorbent assay (ELISA)." Journal of General Virology 54. (1981): 443-448. (01/1981)
  • Langridge, W.H.R. and Henry, J.E.. "Molecular weight and base composition of DNA isolated from Melanoplus sanguinipes entomopoxvirus.." Journal of Invertebrate Pathology 37. (1981): 34-37. (01/1981)
  • McCarthy, W.J., Murphy, T.F., and Langridge, W.H.R.. "Characteristics of the DNA from Lymantria dispar nuclear polyhedrosis virus.." Virology 95. (1979): 593-597. (01/1979)
  • Szalay, A.A., Mackey, C.J., and Langridge, W.H.R.. "Restriction endonucleases and their applications.." Enzyme and Microbial Technology 1. (1979): 154-163. (01/1979)
  • Langridge, W.H.R. and Roberts, D.W.. "The molecular weight of DNA from four entomopoxviruses determined by electron microscopy.." J. Virology 21. (1977): 301-308. (01/1977)
  • Langridge, W.H.R., Komuniecki, P., and DeToma, F.J.. "Isolation and regulatory properties of two glutamate dehydrogenases from the cellular slime mold Dictyostelium discoideum.." Archives of Biochemistry and Biophysics, 178. (1977): 581-587. (01/1977)
  • Langridge, W.H.R., Bozarth, R.F., and Roberts, D.W. . "The base composition of entomopoxvirus DNA.." Virology 76. (1977): 615-620. (01/1977)
  • Langridge, W.H.R. and Roberts, D.W.. "Electron microscopic determination of the molecular weight of DNA from three entomopoxviruses.." Journal of Ultrastructure Research 52. (1975): 135-. (01/1975)
  • Langridge, W.H.R. and DeToma, F.. "Regulation of glutamate dehydrogenase activity during morphogenesis in the cellular slime mould Dictyostelium discoideum.." Fed. Amer. Soc. Exp. Biol., 33. (1974): 1427-. (01/1974)
  • Weir, M.P., Langridge, W.H.R., and Walker, R.W.. "Relationships between oleic acid uptake and lipid metabolism in Mycobacterium smegmatis ." Amer. Rev. Resp. Disease, 106. (1972): 451-457. (01/1972)
  • Wallace, H. and Langridge, W.H.R.. "Differential amphiplasty and control of ribosomal RNA synthesis.." Heredity, 27.1 (1971): 1-13. (01/1971)
  • Wallace, H., Morray, J. and Langridge, W.H.R. . "Alternative model for gene amplification.." Nature New Biol., 230. (1971): 201-203. (01/1971)
  • Langridge, W.H.R., O'Malley, T., and Wallace, H. "Neutral amphiplasty and regulation of the cell cycle of Crepis herbs.." Proc. Natl. Acad. Sci., USA, 67. (1970): 1894-1900. (01/1970)

Books and Chapters

  •  Dequina Nicholas, Oludare Odumosu and William Langridge (2011)Autoantigen based vaccines for Type 1 diabetes. Discovery Medicine. Apr 11, (59): 293-301.   (04/2011 - 11/2011)
  •  William Langridge, Istvan Fodor, Odulare Odumosu and Bela Denes. (2009). Vaccines for Type 1 Diabetes in Type 1 Diabetes Mellitus: Etiology, Diagnosis and Treatment.  Nova Science Publishers, F. Columbus ed. (Accepted. June 31, 2009). (09/2008 - 09/2009)
  • Yu, J., Carter, J.E. and Langridge, W.H.R. . Edible Vaccines, in AVaccines: Delivery Systems. Chapter 16: : Gobel, W. and Dietrich, G. eds., Horizon Press,, 2002. 369 - 397 (01/2002)
  • Carter, J. E., Choi, N.W., Rivers-Khalid, C. and Langridge, W.H.R. . Plant Based Vaccines, in ATransgenic Plants. Chapter 10: : Current Innovations and Future Trends@ N. Stewart ed. Horizon Press,, . 233 - 264

Book Review - Scholarly Journals--Published

  •  Carter, J.E.,Osumosu O, Langridge WHR (2010) Expression of a Ricin Toxin B subunit : Insulin fusion protein in edible plant tissues. Molecular Biotechnology Feb: 44 (2) 90-100.   (01/2010 - 11/2011)
  • (09/2008 - 09/2009)
  • William Langridge, Béla Dénes and István Fodor (2009). Cholera toxin B subunit                           enhancement of vaccines for infectious and autoimmune diseases (Accepted, May, 2009    Current Opinions in Investigational Drugs). (09/2008 - 09/2009)

Abstract

  • (PEER REVIEWED) American Society of Gene Therapy, 12th Annual Meeting, May 27-30, San Diego, CA.   Abstract #950039, "Durable Multicomponent Vaccine Suppression of Diabetes., B. Denes, I. Fodor and W. Langridge, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA. 92350. In this study, fusion genes encoding the diabetes autoantigen glutamic acid decarboxylase (GAD), linked to the immunostimulatory cholera toxin B subunit (CTB-GAD) were delivered alone and in combination with the anti-inflammatory cytokine IL-10 by vaccinia virus infection of juvenile NOD mice. The mice were assessed for long term protection against diabetes progression by measurement of blood glucose levels from 11 to 63 wk of age. Approximately 80% of the mice inoculated with PBS, empty plasmid DNA or parental vaccinia developed hyperglycemia by 33 weeks of age. However, only 55% of the mice inoculated with VV-CTB::GAD and only 20% of mice co-inoculated with VV-CTB::GAD + VV-IL10 developed hyperglycemia over this time period. No further increase in blood glucose levels or diabetes incidence occurred in all immunized animal groups from 33 to 64 wk of age suggesting re-establishment of immunological homeostasis and permanent protection against further diabetes development. Histological analysis of pancreatic tissues isolated from mice inoculated with PBS, empty plasmid or vaccinia virus alone showed almost 100% peri-islet and intra-islet inflammation (insulitis). However, mice inoculated with virus containing the CTB-GAD fusion gene showed an approximate 50% reduction in insulitis. Further, mice co-inoculated with vaccinia virus containing the CTB-GAD and IL-10 genes showed an approximate 75% reduction in pancreatic inflammation. In contrast to un-inoculated mice, splenocytes isolated from 64 wk old mice co-vaccinated with rVV-CTB::GAD and rVV-IL-10 showed a significant reduction in inflammatory IFN-( cytokine secretion and increased secretion of the anti-inflammatory cytokine IL-10. In contrast to individual diabetes immunosuppression therapies, we demonstrate here that combinatorial vaccination strategies relying on vaccinia virus co-delivery of immuno-enhanced autoantigen and anti-inflammatory cytokine DNAs restore effective and durable immunologic homeostasis in NOD mice through suppression of diabetes hyperglycemia to normal blood glucose levels throughout the majority of the lifetime of the prediabetic animal. This effective and inexpensive multifactorial diabetes therapy can now be advanced for clinical confirmation in patients afflicted with or likely to develop Type 1 diabetes. (05/2009)
  • (PEER REVIEWED) Title: Suppression of Type 1 Diabetes by a Vaccinia Virus-Based  Multicomponent Vaccine. W. Langridge, B. Denes, I Fodor. Second International Conference on Advanced Technologies and Treatments for Diabetes, Athens, Greece, February 25-28, 2009. Multifactorial vaccines show promise for more effective autoimmune diabetes immunotherapy than individual immunotherapies. In this study, fusion genes encoding the diabetes autoantigen glutamic acid decarboxylase (GAD), linked to the immunostimulatory cholera toxin B subunit (CTB-GAD) were delivered alone and in combination with the anti-inflammatory cytokine IL-10 by vaccinia virus infection of juvenile NOD mice. The mice were assessed for long term protection against diabetes progression by measurement of blood glucose levels from 11 to 63 wk of age. Approximately 80% of the mice inoculated with PBS, empty plasmid DNA or parental vaccinia developed hyperglycemia by 33 weeks of age. However, only 55% of the mice inoculated with VV-CTB::GAD and only 20% of mice co-inoculated with VV-CTB::GAD + VV-IL10 developed hyperglycemia over this time period. No further increase in blood glucose levels or diabetes incidence occurred in all immunized animal groups from 33 to 64 wk of age suggesting re-establishment of immunological homeostasis and permanent protection against further diabetes development. Histological analysis of pancreatic tissues isolated from mice inoculated with PBS, empty plasmid or vaccinia virus alone showed almost 100% peri-islet and intra-islet inflammation (insulitis). However, mice inoculated with virus containing the CTB-GAD fusion gene showed an approximate 50% reduction in insulitis. Further, mice co-inoculated with vaccinia virus containing the CTB-GAD and IL-10 genes showed an approximate 75% reduction in pancreatic inflammation. In contrast to un-inoculated mice, splenocytes isolated from 64 wk old mice co-vaccinated with rVV-CTB::GAD and rVV-IL-10 showed a significant reduction in inflammatory IFN-( cytokine secretion and increased secretion of the anti-inflammatory cytokine IL-10. In contrast to individual diabetes immunosuppression therapies, we demonstrate here that combinatorial vaccination strategies relying on vaccinia virus co-delivery of immuno-enhanced autoantigen and anti-inflammatory cytokine DNAs restore effective and durable immunologic homeostasis in NOD mice through suppression of diabetes hyperglycemia to normal blood glucose levels throughout the majority of the lifetime of the prediabetic animal. This effective and inexpensive multifactorial diabetes therapy can now be advanced for clinical confirmation in patients afflicted with or likely to develop Type 1 diabetes. (11/2008)
  • (PEER REVIEWED) Denes B., Fodor I. and Langridge W. . "Suppression of Hyperglycemia in NOD Mice After Inoculation with Recombinant Vaccinia Viruses." Molecular Therapy . (2007): #52- . (05/2007)
  • (PEER REVIEWED) Langridge, Denes, N. Fodor, Krausova, Timiryasova, Henderson, Hough, Yu, I. Fodor. "Oral delivery of recombinant vaccinia virus expressing adjuvanted islet autoantigens protects NOD mice from autoimmune diabetes.." Molecular Therapy, 11.1 (2005): 62-62. (06/2005)

Scholarly Journals--Accepted

  •    Daniell  H, Ruiz G,  Denes B, Sandberg L, and Langridge W, (2008). Optimization of codon composition and regulatory elements for expression of the human insulin like growth factor-1 in transgenic tobacco chloroplasts and evaluation of structure and function. (accepted, December, 2008, BMC Biotechnology). Background: Transgenic chloroplasts are ideal bioreactors for recombinant protein production, especially for achievement of high levels of protein expression and proper folding.  Production of therapeutic proteins in leaves provides transgene containment by elimination of reproductive structures.  In this study, human Insulin like Growth Factor is expressed in transgenic chloroplasts for evaluation of structural identity and function. Results: Expression of the synthetic Insulin like Growth Factor 1 gene (IGF-1s, 60% AT) was observed in transformed E. coli. However, no native IGF-1 gene (IGF-1n, 41% AT) product was detected in the western blots. Site-specific integration of the transgenes into the tobacco chloroplast genome was confirmed after transformation using PCR. Southern blot analysis confirmed that the transgenic lines were homoplasmic. The transgenic plant lines had IGF-1s expression levels of 11.3 % of total soluble protein (TSP). The IGF-1n plants contained 9.5% TSP as IGF-1n, suggesting that the chloroplast translation machinery is more flexible than E. coli in codon preference and usage.  The expression of IGF-1 was increased up to 32 % TSP under continuous illumination by the chloroplast light regulatory elements.  IgG-Sepharose affinity column chromatographic separation of Z domain containing chloroplast derived IGF-1 protein, single and two dimensional electrophoresis methods and mass spectrometer analysis confirmed the identity of human IGF-1 in transgenic chloroplasts. Two spots analyzed from 2-D focusing/phoresis acrylamide gel showed the correct amino acid sequence of human IGF-1 and the S. aureus Z-tag.  Cell proliferation assays in human HU-3 cells demonstrated the biological activity of chloroplast derived IGF-1 even in the presence of the S. aureus Z tag. Conclusions: This study demonstrates that the human Insulin like Growth Factor expressed in transgenic chloroplasts is identical to the native protein and is fully functional. The ability to use plant chloroplasts as bioreactors to generate proteins of great economic value that retain their biological activity is an exciting and achievable goal that appears to be within our grasp.  (12/2008)
  • Eun-Ah Shin, Ph.D.; Yong Keun Park, Ph.D.; Kang Oh Lee, Ph.D.; William Henry Langridge,            Ph.D.Jin-Yong Lee, Ph.D. Synthesis and assembly of Porphyromonas gingivalis fimbrial   protein in potato tissues. Molecular Biotechnology (Accepted, May, 2009). (09/2008 - 09/2009)
  • Carter, J.E., Odumosu, O. and Langridge, W.H.R. (2009).  Expression of a Ricin Toxin B Subunit - Insulin Fusion Protein in Potato.  Molecular Biotechnology, (Accepted August,2009). (09/2008 - 09/2009)

Scholarly Journals--Submitted

  • Denes, B., Fodor, I. and Langridge W.H.R., Durable CTB-GAD + IL-10 multicomponent vaccine suppression of diabetes autoimmunity (submitted March, 2009, Molecular Biotechnology). (09/2008 - 09/2009)

Non-Scholarly Journals

  • Langridge W.H.R. "Edible Vaccines." Scientific American Reports 01/12/2006: 46 - 53 (12/2006)
  • William H.R. Langridge" Edible vaccines, ." Scientific American Reports 31 12 1969: 46 - 53 (Present)