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Sample records for antibody concentrations confers

  1. Antibody Engineering and Therapeutics Conference

    PubMed Central

    Almagro, Juan Carlos; Gilliland, Gary L; Scott, Jamie; Larrick, James W; Plückthun, Andreas; Veldman, Trudi; Adams, Gregory P; Parren, Paul WHI; Chester, Kerry A; Bradbury, Andrew; Reichert, Janice M; Huston, James S

    2013-01-01

    The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Biology), who will discuss a systems approach for studying disease that is enabled by emerging technology; Douglas Lauffenburger (Massachusetts Institute of Technology), who will discuss systems analysis of cell communication network dynamics for therapeutic biologics design; David Baker (University of Washington), who will describe computer-based design of smart protein therapeutics; and William Schief (The Scripps Research Institute), who will discuss epitope-focused immunogen design.   In this preview of the conference, the workshop and session chairs share their thoughts on what conference participants may learn in sessions on: (1) three-dimensional structure antibody modeling; (2) identifying clonal lineages from next-generation data sets of expressed VH gene sequences; (3) antibodies in cardiometabolic medicine; (4) the effects of antibody gene variation and usage on the antibody response; (5) directed evolution; (6) antibody pharmacokinetics, distribution and off-target toxicity; (7) use of knowledge-based design to guide development of complementarity-determining regions and epitopes to engineer or elicit the desired antibody; (8) optimizing antibody formats for immunotherapy; (9) antibodies in a complex environment; (10) polyclonal, oligoclonal and bispecific antibodies; (11) antibodies to watch in 2014; and (12) polyreactive antibodies and polyspecificity.

  2. Antibody engineering and therapeutics conference

    PubMed Central

    Larrick, James W; Parren, Paul WHI; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A; Burton, Dennis R; Adams, Gregory P; Weiner, Louis M; Scott, Jamie K; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M

    2014-01-01

    The 25th anniversary of the Antibody Engineering & Therapeutics Conference, the Annual Meeting of The Antibody Society, will be held in Huntington Beach, CA, December 7–11, 2014. Organized by IBC Life Sciences, the event will celebrate past successes, educate participants on current activities and offer a vision of future progress in the field. Keynote addresses will be given by academic and industry experts Douglas Lauffenburger (Massachusetts Institute of Technology), Ira Pastan (National Cancer Institute), James Wells (University of California, San Francisco), Ian Tomlinson (GlaxoSmithKline) and Anthony Rees (Rees Consulting AB and Emeritus Professor, University of Bath). These speakers will provide updates of their work, placed in the context of the substantial growth of the industry over the past 25 years. PMID:25517297

  3. Conference report: hot topics in antibody-drug conjugate development.

    PubMed

    Thudium, Karen; Bilic, Sanela

    2013-12-01

    American Association of Pharmaceutical Scientists National Biotechnology Conference Sheraton San Diego Hotel and Marina, San Diego, CA, USA, 19-23 May 2013 The National Biotechnology Conference, is a premier meeting for biotechnology professionals covering a broad range of hot topics in the biotechnology industry. Attracting participants from academia, industry and regulatory, this meeting features sessions that aim to address emerging subjects of interest and allows for open exchange between scientists. The 2013 conference featured leading researchers in the fields of antibody-drug conjugates (ADCs) and immunogenicity. Herein, we present a summary of the ADC hot topics, including bioanalytical and PK considerations, quantitative evaluation of the impact of immunogenicity and ADME to understand ADC drug-drug interactions, and clinical considerations for ADC development. This article aims to summarize the recommendations that were made by the speakers during various sessions throughout the conference.

  4. IBC’s 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics International Conferences and the 2012 Annual Meeting of The Antibody Society

    PubMed Central

    Klöhn, Peter-Christian; Wuellner, Ulrich; Zizlsperger, Nora; Zhou, Yu; Tavares, Daniel; Berger, Sven; Zettlitz, Kirstin A.; Proetzel, Gabriele; Yong, May; Begent, Richard H.J.; Reichert, Janice M

    2013-01-01

    The 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences, and the 2012 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 3–6, 2012 in San Diego, CA. The meeting drew over 800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a prelude to the main events, a pre-conference workshop held on December 2, 2012 focused on intellectual property issues that impact antibody engineering. The Antibody Engineering Conference was composed of six sessions held December 3–5, 2012: (1) From Receptor Biology to Therapy; (2) Antibodies in a Complex Environment; (3) Antibody Targeted CNS Therapy: Beyond the Blood Brain Barrier; (4) Deep Sequencing in B Cell Biology and Antibody Libraries; (5) Systems Medicine in the Development of Antibody Therapies/Systematic Validation of Novel Antibody Targets; and (6) Antibody Activity and Animal Models. The Antibody Therapeutics conference comprised four sessions held December 4–5, 2012: (1) Clinical and Preclinical Updates of Antibody-Drug Conjugates; (2) Multifunctional Antibodies and Antibody Combinations: Clinical Focus; (3) Development Status of Immunomodulatory Therapeutic Antibodies; and (4) Modulating the Half-Life of Antibody Therapeutics. The Antibody Society’s special session on applications for recording and sharing data based on GIATE was held on December 5, 2012, and the conferences concluded with two combined sessions on December 5–6, 2012: (1) Development Status of Early Stage Therapeutic Antibodies; and (2) Immunomodulatory Antibodies for Cancer Therapy. PMID:23575266

  5. Effects of medium concentration on antibody production

    NASA Technical Reports Server (NTRS)

    Williams, J.

    1984-01-01

    Antibody production by two different cell lines was measured as the media were supplemented with varied amounts of glucose and fetal bovine serum. Both cell lines elaborated antidinitrophenyl hapten antibodies. Two basic media were used: RPMI 1640 and Dulbecco's modified Eagle's medium. The production of antibodies was followed from 0 to 180 h and was assayed by radioimmunoassay.

  6. Effects of medium concentration on antibody production

    NASA Technical Reports Server (NTRS)

    Williams, J.

    1984-01-01

    Antibody production by two different cell lines was measured as the media were supplemented with varied amounts of glucose and fetal bovine serum. Both cell lines elaborated antidinitrophenyl hapten antibodies. Two basic media were used: RPMI 1640 and Dulbecco's modified Eagle's medium. The production of antibodies was followed from 0 to 180 h and was assayed by radioimmunoassay.

  7. Serum vaccine antibody concentrations in children exposed to perfluorinated compounds.

    PubMed

    Grandjean, Philippe; Andersen, Elisabeth Wreford; Budtz-Jørgensen, Esben; Nielsen, Flemming; Mølbak, Kåre; Weihe, Pal; Heilmann, Carsten

    2012-01-25

    Perfluorinated compounds (PFCs) have emerged as important food contaminants. They cause immune suppression in a rodent model at serum concentrations similar to those occurring in the US population, but adverse health effects of PFC exposure are poorly understood. To determine whether PFC exposure is associated with antibody response to childhood vaccinations. Prospective study of a birth cohort from the National Hospital in the Faroe Islands. A total of 656 consecutive singleton births were recruited during 1997-2000, [corrected] and 587 participated in follow-up through 2008. Serum antibody concentrations against tetanus and diphtheria toxoids at ages 5 and 7 years. Similar to results of prior studies in the United States, the PFCs with the highest serum concentrations were perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Among PFCs in maternal pregnancy serum, PFOS showed the strongest negative correlations with antibody concentrations at age 5 years, for which a 2-fold greater concentration of exposure was associated with a difference of -39% (95% CI, -55% to -17%) in the diphtheria antibody concentration. PFCs in the child's serum at age 5 years showed uniformly negative associations with antibody levels, especially at age 7 years, except that the tetanus antibody level following PFOS exposure was not statistically significant. In a structural equation model, a 2-fold greater concentration of major PFCs in child serum was associated with a difference of -49% (95% CI, -67% to -23%) in the overall antibody concentration. A 2-fold increase in PFOS and PFOA concentrations at age 5 years was associated with odds ratios between 2.38 (95% CI, 0.89 to 6.35) and 4.20 (95% CI, 1.54 to 11.44) for falling below a clinically protective level of 0.1 IU/mL for tetanus and diphtheria antibodies at age 7 years. Elevated exposures to PFCs were associated with reduced humoral immune response to routine childhood immunizations in children aged 5 and 7 years.

  8. Antibody response to inactivated influenza vaccines of various antigenic concentrations.

    PubMed

    Sullivan, K M; Monto, A S; Foster, D A

    1990-02-01

    Four inactivated influenza vaccines (containing the recommended antigens for the 1985-1986 influenza season) of various antigenic concentration levels were randomly administered to 140 study participants. The effect of the increasing antigen concentration resulted in significantly higher influenza hemagglutination inhibition (HI) antibody levels 3 weeks after vaccination for the A/H1N1 antigen but not for the A/H3N2 or B antigens. Also, at 3 weeks after vaccination, there were significantly lower antibody titer levels associated with increasing age for the A/H1N1 and B antigens (adjusting for the prevaccination antibody titer and antigen content).

  9. HIV-1 resistance to neutralizing antibodies: Determination of antibody concentrations leading to escape mutant evolution.

    PubMed

    Magnus, Carsten; Reh, Lucia; Trkola, Alexandra

    2016-06-15

    Broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) are considered vital components of novel therapeutics and blueprints for vaccine research. Yet escape to even the most potent of these antibodies is imminent in natural infection. Measures to define antibody efficacy and prevent mutant selection are thus urgently needed. Here, we derive a mathematical framework to predict the concentration ranges for which antibody escape variants can outcompete their viral ancestors, referred to as mutant selection window (MSW). When determining the MSW, we focus on the differential efficacy of neutralizing antibodies against HIV-1 in two canonical infection routes, free-virus infection and cell-cell transmission. The latter has proven highly effective in vitro suggesting its importance for both in vivo spread as well as for escaping targeted intervention strategies. We observed a range of MSW patterns that highlight the potential of mutants to arise in both transmission pathways and over wide concentration ranges. Most importantly, we found that only when the arising mutant has both, residual sensitivity to the neutralizing antibody and reduced infectivity compared to the parental virus, antibody dosing outside of the MSW to restrict mutant selection is possible. Emergence of mutants that provide complete escape and have no considerable fitness loss cannot be prevented by adjusting antibody doses. The latter may in part explain the ubiquitous resistance to neutralizing antibodies observed in natural infection and antibody treatment. Based on our findings, combinations of antibodies targeting different epitopes should be favored for antibody-based interventions as this may render complete resistance less likely to occur and also increase chances that multiple escapes result in severe fitness loss of the virus making longer-term antibody treatment more feasible. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  10. [Anti-A antibodies and bacterial contamination of platelet concentrates].

    PubMed

    García-Erce, J A; Seoane, A; Solano, V M; Salvador Osuna, C; Pérez-Layo, A; Gómez-Arteta, E; Gimeno, J J

    1999-12-01

    The possible ABO group antibodies protective function against several infections has been classically described. We analyze the platelet concentrates (PC) bacterial control results and their ABO antibodies. We studied 245 outdated PCs (> 5 days). The samples were sterilely collected for adequate microbiological investigation studies on sheep-blood agar plates. If bacterial growth is found, the microbiological identification is performed on the basis of standard tests, the specific anti-biotype being achieved by disk-diffusion method on Müeller-Hinton agar plates, and the red cell concentrate was analyzed. Bacterial growth by negative coagulase Staphylococcus was found in 10 PCs (4.1%; CI95%; 1.97-7.37). The contaminated PCs lacked natural anti-A antibodies. There were no statistical differences when we analyzed the PC's age, colour or blood group. The anti-A antibodies may be a protective factor versus PCs contamination caused by resident bacteria.

  11. IBC’s 23rd Antibody Engineering and 10th Antibody Therapeutics Conferences and the Annual Meeting of The Antibody Society

    PubMed Central

    Marquardt, John; Begent, Richard H.J.; Chester, Kerry; Huston, James S.; Bradbury, Andrew; Scott, Jamie K.; Thorpe, Philip E.; Veldman, Trudi; Reichert, Janice M.; Weiner, Louis M.

    2012-01-01

    Now in its 23rd and 10th years, respectively, the Antibody Engineering and Antibody Therapeutics conferences are the Annual Meeting of The Antibody Society. The scientific program covers the full spectrum of challenges in antibody research and development from basic science through clinical development. In this preview of the conferences, the chairs provide their thoughts on sessions that will allow participants to track emerging trends in (1) the development of next-generation immunomodulatory antibodies; (2) the complexity of the environment in which antibodies must function; (3) antibody-targeted central nervous system (CNS) therapies that cross the blood brain barrier; (4) the extension of antibody half-life for improved efficacy and pharmacokinetics (PK)/pharmacodynamics (PD); and (5) the application of next generation DNA sequencing to accelerate antibody research. A pre-conference workshop on Sunday, December 2, 2012 will update participants on recent intellectual property (IP) law changes that affect antibody research, including biosimilar legislation, the America Invents Act and recent court cases. Keynote presentations will be given by Andreas Plückthun (University of Zürich), who will speak on engineering receptor ligands with powerful cellular responses; Gregory Friberg (Amgen Inc.), who will provide clinical updates of bispecific antibodies; James D. Marks (University of California, San Francisco), who will discuss a systems approach to generating tumor targeting antibodies; Dario Neri (Swiss Federal Institute of Technology Zürich), who will speak about delivering immune modulators at the sites of disease; William M. Pardridge (University of California, Los Angeles), who will discuss delivery across the blood-brain barrier; and Peter Senter (Seattle Genetics, Inc.), who will present his vision for the future of antibody-drug conjugates. For more information on these meetings or to register to attend, please visit www.IBCLifeSciences.com/Antibody

  12. IBC's 23rd Antibody Engineering and 10th Antibody Therapeutics Conferences and the Annual Meeting of The Antibody Society: December 2-6, 2012, San Diego, CA.

    PubMed

    Marquardt, John; Begent, Richard H J; Chester, Kerry; Huston, James S; Bradbury, Andrew; Scott, Jamie K; Thorpe, Philip E; Veldman, Trudi; Reichert, Janice M; Weiner, Louis M

    2012-01-01

    Now in its 23rd and 10th years, respectively, the Antibody Engineering and Antibody Therapeutics conferences are the Annual Meeting of The Antibody Society. The scientific program covers the full spectrum of challenges in antibody research and development from basic science through clinical development. In this preview of the conferences, the chairs provide their thoughts on sessions that will allow participants to track emerging trends in (1) the development of next-generation immunomodulatory antibodies; (2) the complexity of the environment in which antibodies must function; (3) antibody-targeted central nervous system (CNS) therapies that cross the blood brain barrier; (4) the extension of antibody half-life for improved efficacy and pharmacokinetics (PK)/pharmacodynamics (PD); and (5) the application of next generation DNA sequencing to accelerate antibody research. A pre-conference workshop on Sunday, December 2, 2012 will update participants on recent intellectual property (IP) law changes that affect antibody research, including biosimilar legislation, the America Invents Act and recent court cases. Keynote presentations will be given by Andreas Plückthun (University of Zürich), who will speak on engineering receptor ligands with powerful cellular responses; Gregory Friberg (Amgen Inc.), who will provide clinical updates of bispecific antibodies; James D. Marks (University of California, San Francisco), who will discuss a systems approach to generating tumor targeting antibodies; Dario Neri (Swiss Federal Institute of Technology Zürich), who will speak about delivering immune modulators at the sites of disease; William M. Pardridge (University of California, Los Angeles), who will discuss delivery across the blood-brain barrier; and Peter Senter (Seattle Genetics, Inc.), who will present his vision for the future of antibody-drug conjugates. For more information on these meetings or to register to attend, please visit www.IBCLifeSciences.com/Antibody

  13. Serum Vaccine Antibody Concentrations in Children Exposed to Perfluorinated Compounds

    PubMed Central

    Grandjean, Philippe; Andersen, Elisabeth Wreford; Budtz-Jørgensen, Esben; Nielsen, Flemming; Mølbak, Kåre; Weihe, Pal; Heilmann, Carsten

    2015-01-01

    Context Perfluorinated compounds (PFCs) have emerged as important food contaminants. They cause immune suppression in a rodent model at serum concentrations similar to those occurring in the US population, but adverse health effects of PFC exposure are poorly understood. Objective To determine whether PFC exposure is associated with antibody response to childhood vaccinations. Design, Setting, and Participants Prospective study of a birth cohort from the National Hospital in the Faroe Islands. A total of 656 consecutive singleton births were recruited during 1997-2000, and 587 participated in follow-up through 2008. Main Outcome Measures Serum antibody concentrations against tetanus and diphtheria toxoids at ages 5 and 7 years. Results Similar to results of prior studies in the United States, the PFCs with the highest serum concentrations were perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Among PFCs in maternal pregnancy serum, PFOS showed the strongest negative correlations with antibody concentrations at age 5 years, for which a 2-fold greater concentration of exposure was associated with a difference of −39% (95% CI, −55% to −17%) in the diphtheria antibody concentration. PFCs in the child’s serum at age 5 years showed uniformly negative associations with antibody levels, especially at age 7 years, except that the tetanus antibody level following PFOS exposure was not statistically significant. In a structural equation model, a 2-fold greater concentration of major PFCs in child serum was associated with a difference of −49% (95% CI, −67% to −23%) in the overall antibody concentration. A 2-fold increase in PFOS and PFOA concentrations at age 5 years was associated with odds ratios between 2.38 (95% CI, 0.89 to 6.35) and 4.20 (95% CI, 1.54 to 11.44) for falling below a clinically protective level of 0.1 IU/mL for tetanus and diphtheria antibodies at age 7 years. Conclusion Elevated exposures to PFCs were associated with

  14. IBC's 22nd Annual Antibody Engineering and 9th Annual Antibody Therapeutics International Conferences and the 2011 Annual Meeting of The Antibody Society, December 5–8, 2011, San Diego, CA

    PubMed Central

    Nilvebrant, Johan; Dunlop, D Cameron; Sircar, Aroop; Wurch, Thierry; Falkowska, Emilia; Helguera, Gustavo; Piccione, Emily C; Brack, Simon; Berger, Sven

    2012-01-01

    The 22nd Annual Antibody Engineering and 9th Annual Antibody Therapeutics international conferences, and the 2011 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 5–8, 2011 in San Diego, CA. The meeting drew ∼800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a preview to the main events, a pre-conference workshop held on December 4, 2011 focused on antibodies as probes of structure. The Antibody Engineering Conference comprised eight sessions: (1) structure and dynamics of antibodies and their membrane receptor targets; (2) model-guided generation of binding sites; (3) novel selection strategies; (4) antibodies in a complex environment: targeting intracellular and misfolded proteins; (5) rational vaccine design; (6) viral retargeting with engineered binding molecules; (7) the biology behind potential blockbuster antibodies and (8) antibodies as signaling modifiers: where did we go right, and can we learn from success? The Antibody Therapeutics Conference comprised five sessions: (1) Twenty-five years of therapeutic antibodies: lessons learned and future challenges; (2) preclinical and early stage development of antibody therapeutics; (3) next generation anti-angiogenics; (4) updates of clinical stage antibody therapeutics and (5) antibody drug conjugates and bispecific antibodies. PMID:22453091

  15. IBC's 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences and the 2012 Annual Meeting of The Antibody Society: December 3-6, 2012, San Diego, CA.

    PubMed

    Klöhn, Peter-Christian; Wuellner, Ulrich; Zizlsperger, Nora; Zhou, Yu; Tavares, Daniel; Berger, Sven; Zettlitz, Kirstin A; Proetzel, Gabriele; Yong, May; Begent, Richard H J; Reichert, Janice M

    2013-01-01

    The 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences, and the 2012 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 3-6, 2012 in San Diego, CA. The meeting drew over 800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a prelude to the main events, a pre-conference workshop held on December 2, 2012 focused on intellectual property issues that impact antibody engineering. The Antibody Engineering Conference was composed of six sessions held December 3-5, 2012: (1) From Receptor Biology to Therapy; (2) Antibodies in a Complex Environment; (3) Antibody Targeted CNS Therapy: Beyond the Blood Brain Barrier; (4) Deep Sequencing in B Cell Biology and Antibody Libraries; (5) Systems Medicine in the Development of Antibody Therapies/Systematic Validation of Novel Antibody Targets; and (6) Antibody Activity and Animal Models. The Antibody Therapeutics conference comprised four sessions held December 4-5, 2012: (1) Clinical and Preclinical Updates of Antibody-Drug Conjugates; (2) Multifunctional Antibodies and Antibody Combinations: Clinical Focus; (3) Development Status of Immunomodulatory Therapeutic Antibodies; and (4) Modulating the Half-Life of Antibody Therapeutics. The Antibody Society's special session on applications for recording and sharing data based on GIATE was held on December 5, 2012, and the conferences concluded with two combined sessions on December 5-6, 2012: (1) Development Status of Early Stage Therapeutic Antibodies; and (2) Immunomodulatory Antibodies for Cancer Therapy.

  16. Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development

    PubMed Central

    Tomar, Dheeraj S.; Kumar, Sandeep; Singh, Satish K.; Goswami, Sumit; Li, Li

    2016-01-01

    ABSTRACT Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored. PMID:26736022

  17. Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development.

    PubMed

    Tomar, Dheeraj S; Kumar, Sandeep; Singh, Satish K; Goswami, Sumit; Li, Li

    2016-01-01

    Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored.

  18. Live SIV vaccine correlate of protection: local antibody production and concentration on the path of virus entry

    PubMed Central

    Li, Qingsheng; Zeng, Ming; Duan, Lijie; Voss, James E.; Smith, Anthony J.; Pambuccian, Stefan; Shang, Liang; Wietgrefe, Stephen; Southern, Peter J.; Reilly, Cavan S.; Skinner, Pamela J.; Zupancic, Mary L.; Carlis, John V.; Piatak, Michael; Waterman, Diane; Reeves, R. Keith; Masek-Hammerman, Katherine; Derdeyn, Cynthia A.; Alpert, Michael D.; Evans, David T.; Kohler, Heinz; Muller, Sybille; Robinson, James; Lifson, Jeffrey D.; Burton, Dennis R.; Johnson, R. Paul; Haase, Ashley T.

    2014-01-01

    We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG antibodies reactive with viral envelope glycoprotein gp41 trimers, and these antibodies are concentrated on the path of virus entry by the neonatal Fc receptor (FcRn) in cervical reserve epithelium and in vaginal epithelium. This local antibody production and delivery system correlated spatially and temporally with the maturation of local protection against high dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of antibodies at mucosal frontlines could aid development of an effective vaccine to protect women against HIV-1. PMID:25135832

  19. IBC's 22nd Annual Antibody Engineering and 9th Annual Antibody Therapeutics International Conferences and the 2011 Annual Meeting of The Antibody Society, December 5-8, 2011, San Diego, CA.

    PubMed

    Nilvebrant, Johan; Dunlop, D Cameron; Sircar, Aroop; Wurch, Thierry; Falkowska, Emilia; Reichert, Janice M; Helguera, Gustavo; Piccione, Emily C; Brack, Simon; Berger, Sven

    2012-01-01

    The 22nd Annual Antibody Engineering and 9th Annual Antibody Therapeutics international conferences, and the 2011 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 5-8, 2011 in San Diego, CA. The meeting drew ~800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a preview to the main events, a pre-conference workshop held on December 4, 2011 focused on antibodies as probes of structure. The Antibody Engineering Conference comprised eight sessions: (1) structure and dynamics of antibodies and their membrane receptor targets; (2) model-guided generation of binding sites; (3) novel selection strategies; (4) antibodies in a complex environment: targeting intracellular and misfolded proteins; (5) rational vaccine design; (6) viral retargeting with engineered binding molecules; (7) the biology behind potential blockbuster antibodies and (8) antibodies as signaling modifiers: where did we go right, and can we learn from success? The Antibody Therapeutics session comprised five sessions: (1)Twenty-five years of therapeutic antibodies: lessons learned and future challenges; (2) preclinical and early stage development of antibody therapeutics; (3) next generation anti-angiogenics; (4) updates of clinical stage antibody therapeutics and (5) antibody drug conjugates and bispecific antibodies.

  20. Hierarchical Cluster Formation in Concentrated Monoclonal Antibody Formulations

    NASA Astrophysics Data System (ADS)

    Godfrin, P. Douglas; Zarzar, Jonathan; Zarraga, Isidro Dan; Porcar, Lionel; Falus, Peter; Wagner, Norman; Liu, Yun

    Reversible cluster formation has been identified as an underlying cause of large solution viscosities observed in some concentrated monoclonal antibody (mAb) formulations. As high solution viscosity prevents the use of subcutaneous injection as a delivery method for some mAbs, a fundamental understanding of the interactions responsible for high viscosities in concentrated mAb solutions is of significant relevance to mAb applications in human health care as well as of intellectual interest. Here, we present a detailed investigation of a well-studied IgG1 based mAb to relate the short time dynamics and microstructure to significant viscosity changes over a range of pharmaceutically relevant physiochemical conditions. Using a combination of experimental techniques, it is found that upon adding Na2SO4, these antibodies dimerize in solution. Proteins form strongly bounded reversible dimers at dilute concentrations that, when concentrated, interact with each other to form loosely bounded, large, transient clusters. The combined effect of forming strongly bounded dimers and a large transient network is a significant increase in the solution viscosity. Strongly bounded, reversible dimers may exist in many IgG1 based mAb systems such that these results contribute to a more comprehensive understanding of the physical mechanisms producing high viscosities in concentrated protein solutions.

  1. Report from a consensus conference on antibody-mediated rejection in heart transplantation

    PubMed Central

    Kobashigawa, Jon; Crespo-Leiro, Maria G.; Ensminger, Stephan M.; Reichenspurner, Hermann; Angelini, Annalisa; Berry, Gerald; Burke, Margaret; Czer, Lawrence; Hiemann, Nicola; Kfoury, Abdallah G.; Mancini, Donna; Mohacsi, Paul; Patel, Jignesh; Pereira, Naveen; Platt, Jeffrey L.; Reed, Elaine F.; Reinsmoen, Nancy; Rodriguez, E. Rene; Rose, Marlene L.; Russell, Stuart D.; Starling, Randy; Suciu-Foca, Nicole; Tallaj, Jose; Taylor, David O.; Van Bakel, Adrian; West, Lori; Zeevi, Adriana; Zuckermann, Andreas

    2012-01-01

    BACKGROUND The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation. METHODS The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus. RESULTS A tentative pathology diagnosis of AMR was established, however, the pathologist felt that further discussion was needed prior to a formal recommendation for AMR diagnosis. One of the most important outcomes of this conference was that a clinical definition for AMR (cardiac dysfunction and/or circulating donor-specific antibody) was no longer believed to be required due to recent publications demonstrating that asymptomatic (no cardiac dysfunction) biopsy-proven AMR is associated with subsequent greater mortality and greater development of cardiac allograft vasculopathy. It was also noted that donor-specific antibody is not always detected during AMR episodes as the antibody may be adhered to the donor heart. Finally, recommendations were made for the timing for specific staining of endomyocardial biopsy specimens and the frequency by which circulating antibodies should be assessed. Recommendations for management and future clinical trials were also provided. CONCLUSIONS The AMR Consensus Conference brought together clinicians, pathologists and immunologists to further the understanding of AMR. Progress was made toward a pathology AMR grading scale and consensus was accomplished regarding several clinical issues. PMID:21300295

  2. Report from a consensus conference on antibody-mediated rejection in heart transplantation.

    PubMed

    Kobashigawa, Jon; Crespo-Leiro, Maria G; Ensminger, Stephan M; Reichenspurner, Hermann; Angelini, Annalisa; Berry, Gerald; Burke, Margaret; Czer, Lawrence; Hiemann, Nicola; Kfoury, Abdallah G; Mancini, Donna; Mohacsi, Paul; Patel, Jignesh; Pereira, Naveen; Platt, Jeffrey L; Reed, Elaine F; Reinsmoen, Nancy; Rodriguez, E Rene; Rose, Marlene L; Russell, Stuart D; Starling, Randy; Suciu-Foca, Nicole; Tallaj, Jose; Taylor, David O; Van Bakel, Adrian; West, Lori; Zeevi, Adriana; Zuckermann, Andreas

    2011-03-01

    The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation. The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus. A tentative pathology diagnosis of AMR was established, however, the pathologist felt that further discussion was needed prior to a formal recommendation for AMR diagnosis. One of the most important outcomes of this conference was that a clinical definition for AMR (cardiac dysfunction and/or circulating donor-specific antibody) was no longer believed to be required due to recent publications demonstrating that asymptomatic (no cardiac dysfunction) biopsy-proven AMR is associated with subsequent greater mortality and greater development of cardiac allograft vasculopathy. It was also noted that donor-specific antibody is not always detected during AMR episodes as the antibody may be adhered to the donor heart. Finally, recommendations were made for the timing for specific staining of endomyocardial biopsy specimens and the frequency by which circulating antibodies should be assessed. Recommendations for management and future clinical trials were also provided. The AMR Consensus Conference brought together clinicians, pathologists and immunologists to further the understanding of AMR. Progress was made toward a pathology AMR grading scale and consensus was accomplished regarding several clinical issues. Copyright © 2011 International Society for Heart and Lung Transplantation. All rights reserved.

  3. Antibody engineering and therapeutics conference. The annual meeting of the antibody society, Huntington Beach, CA, December 7-11, 2014.

    PubMed

    Larrick, James W; Parren, Paul W H I; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A; Burton, Dennis R; Adams, Gregory P; Weiner, Louis M; Scott, Jamie K; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M

    2014-01-01

    The 25th anniversary of the Antibody Engineering & Therapeutics Conference, the Annual Meeting of The Antibody Society, will be held in Huntington Beach, CA, December 7-11, 2014. Organized by IBC Life Sciences, the event will celebrate past successes, educate participants on current activities and offer a vision of future progress in the field. Keynote addresses will be given by academic and industry experts Douglas Lauffenburger (Massachusetts Institute of Technology), Ira Pastan (National Cancer Institute), James Wells (University of California, San Francisco), Ian Tomlinson (GlaxoSmithKline) and Anthony Rees (Rees Consulting AB and Emeritus Professor, University of Bath). These speakers will provide updates of their work, placed in the context of the substantial growth of the industry over the past 25 years.

  4. An antibody that confers plant disease resistance targets a membrane-bound glyoxal oxidase in Fusarium.

    PubMed

    Song, Xiu-Shi; Xing, Shu; Li, He-Ping; Zhang, Jing-Bo; Qu, Bo; Jiang, Jin-He; Fan, Chao; Yang, Peng; Liu, Jin-Long; Hu, Zu-Quan; Xue, Sheng; Liao, Yu-Cai

    2016-05-01

    Plant germplasm resources with natural resistance against globally important toxigenic Fusarium are inadequate. CWP2, a Fusarium genus-specific antibody, confers durable resistance to different Fusarium pathogens that infect cereals and other crops, producing mycotoxins. However, the nature of the CWP2 target is not known. Thus, investigation of the gene coding for the CWP2 antibody target will likely provide critical insights into the mechanism underlying the resistance mediated by this disease-resistance antibody. Immunoblots and mass spectrometry analysis of two-dimensional electrophoresis gels containing cell wall proteins from Fusarium graminearum (Fg) revealed that a glyoxal oxidase (GLX) is the CWP2 antigen. Cellular localization studies showed that GLX is localized to the plasma membrane. This GLX efficiently catalyzes hydrogen peroxide production; this enzymatic activity was specifically inhibited by the CWP2 antibody. GLX-deletion strains of Fg, F. verticillioides (Fv) and F. oxysporum had significantly reduced virulence on plants. The GLX-deletion Fg and Fv strains had markedly reduced mycotoxin accumulation, and the expression of key genes in mycotoxin metabolism was downregulated. This study reveals a single gene-encoded and highly conserved cellular surface antigen that is specifically recognized by the disease-resistance antibody CWP2 and regulates both virulence and mycotoxin biosynthesis in Fusarium species.

  5. IBC's 21st Annual Antibody Engineering and 8th Annual Antibody Therapeutics International Conferences and 2010 Annual Meeting of the Antibody Society. December 5-9, 2010, San Diego, CA USA.

    PubMed

    Arnett, Samantha O; Teillaud, Jean-Luc; Wurch, Theirry; Reichert, Janice M; Dunlop, Cameron; Huber, Michael

    2011-01-01

    The 21st Annual Antibody Engineering and 8th Annual Antibody Therapeutics international conferences, and the 2010 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 5-9, 2010 in San Diego, CA. The conferences were organized with a focus on antibody engineering only on the first day and a joint engineering/therapeutics session on the last day. Delegates could select from presentations that occurred in two simultaneous sessions on days 2 and 3. Day 1 included presentations on neutralizing antibodies and the identification of vaccine targets, as well as a historical overview of 20 years of phage display utilization. Topics presented in the Antibody Engineering sessions on day 2 and 3 included antibody biosynthesis, structure and stability; antibodies in a complex environment; antibody half-life; and targeted nanoparticle therapeutics. In the Antibody Therapeutics sessions on days 2 and 3, preclinical and early stage development and clinical updates of antibody therapeutics, including TRX518, SYM004, MM111, PRO140, CVX-241, ASG-5ME, U3-1287 (AMG888), R1507 and trastuzumab emtansine, were discussed, and perspectives were provided on the development of biosimilar and biobetter antibodies, including coverage of regulatory and intellectual property issues. The joint engineering/therapeutics session on the last day focused on bispecific and next-generation antibodies.

  6. Reversible cluster formation in concentrated monoclonal antibody solutions

    NASA Astrophysics Data System (ADS)

    Godfrin, P. Douglas; Porcar, Lionel; Falus, Peter; Zarraga, Isidro; Wagner, Norm; Liu, Yun

    2015-03-01

    Protein cluster formation in solution is of fundamental interest for both academic research and industrial applications. Recently, industrial scientists are also exploring the effect of reversible cluster formation on biopharmaceutical processing and delivery. However, despite of its importance, the understanding of protein clusters at concentrated solutions remains scientifically very challenging. Using the neutron spin echo technique to study the short time dynamics of proteins in solutions, we have recently systematically studied cluster formation in a few monoclonal antibody (mAb) solutions and their relation with solution viscosity. We show that the existence of anisotropic attraction can cause the formation of finite sized clusters, which increases the solution viscosity. Interestingly, once clusters form at relatively low concentrations, the average size of clusters in solutions remains almost constant over a wide range of concentrations similar to that of micelle formation. For a different mAb we have also investigated, the attraction is mostly induced by hydrophobic patches. As a result, these mAbs form large clusters with loosely linked proteins. In both cases, the formation of clusters all increases the solution viscosity substantially. However, due to different physics origins of cluster formation, solutions viscosities for these two different types of mAbs need to be controlled by different ways.

  7. Kinetics of Monoclonal Antibody Aggregation from Dilute toward Concentrated Conditions.

    PubMed

    Nicoud, Lucrèce; Jagielski, Jakub; Pfister, David; Lazzari, Stefano; Massant, Jan; Lattuada, Marco; Morbidelli, Massimo

    2016-04-07

    Gaining understanding on the aggregation behavior of proteins under concentrated conditions is of both fundamental and industrial relevance. Here, we study the aggregation kinetics of a model monoclonal antibody (mAb) under thermal stress over a wide range of protein concentrations in various buffer solutions. We follow experimentally the monomer depletion and the aggregate growth by size exclusion chromatography with inline light scattering. We describe the experimental results in the frame of a kinetic model based on population balance equations, which allows one to discriminate the contributions of the conformational and of the colloidal stabilities to the global aggregation rate. Finally, we propose an expression for the aggregation rate constant, which accounts for solution viscosity, protein-protein interactions, as well as aggregate compactness. All these effects can be quantified by light scattering techniques. It is found that the model describes well the experimental data under dilute conditions. Under concentrated conditions, good model predictions are obtained when the solution pH is far below the isoelectric point (pI) of the mAb. However, peculiar effects arise when the solution pH is increased toward the mAb pI, and possible explanations are discussed.

  8. A method to confer Protein L binding ability to any antibody fragment.

    PubMed

    Lakhrif, Zineb; Pugnière, Martine; Henriquet, Corinne; di Tommaso, Anne; Dimier-Poisson, Isabelle; Billiald, Philippe; Juste, Matthieu O; Aubrey, Nicolas

    2016-01-01

    Recombinant antibody single-chain variable fragments (scFv) are difficult to purify homogeneously from a protein complex mixture. The most effective, specific and fastest method of purification is an affinity chromatography on Protein L (PpL) matrix. This protein is a multi-domain bacterial surface protein that is able to interact with conformational patterns on kappa light chains. It mainly recognizes amino acid residues located at the VL FR1 and some residues in the variable and constant (CL) domain. Not all kappa chains are recognized, however, and the lack of CL can reduce the interaction. From a scFv composed of IGKV10-94 according to IMGT®, it is possible, with several mutations, to transfer the motif from the IGKV12-46 naturally recognized by the PpL, and, with the single mutation T8P, to confer PpL recognition with a higher affinity. A second mutation S24R greatly improves the affinity, in particular by modifying the dissociation rate (kd). The equilibrium dissociation constant (KD) was measured at 7.2 10(-11) M by surface plasmon resonance. It was possible to confer PpL recognition to all kappa chains. This protein interaction can be modulated according to the characteristics of scFv (e.g., stability) and their use with conjugated PpL. This work could be extrapolated to recombinant monoclonal antibodies, and offers an alternative for protein A purification and detection.

  9. Feasibility of antibody-poly(glutamic acid) complexes: preparation of high-concentration antibody formulations and their pharmaceutical properties.

    PubMed

    Izaki, Shunsuke; Kurinomaru, Takaaki; Maruyama, Takuya; Uchida, Takayuki; Handa, Kenji; Kimoto, Tomoaki; Shiraki, Kentaro

    2015-06-01

    Development of high-concentration antibody formulations for subcutaneous administration remains challenging. Recently, a precipitation-redissolution method was proposed to prepare suspensions or precipitates of salt-dissociable protein-poly(amino acid) complexes. To elucidate the utility of this method for protein therapy, we investigated the feasibility of a precipitation-redissolution method using poly(amino acid) for high-concentration antibody formulation. Omalizumab and adalimumab formulations of 150 mg/mL could be prepared using poly-l-glutamic acid (polyE) from low-concentration stock solutions. Enzyme-linked immunosorbent assay, circular dichroism, and size-exclusion chromatography revealed that the formation of antibody-polyE complex and precipitation-redissolution process did not significantly affect the immunoreactivity or secondary structure of the antibodies. The precipitation-redissolution method was less time-consuming and more effective than lyophilization-redissolution, evaporation-redissolution, and ultrafiltration from the viewpoint of final yield. Scalability was confirmed from 400 μL to 1.0 L. The general toxicity and pharmacokinetic profiles of the antibody-polyE complex formulations were similar to those of conventional antibody formulations. These results suggested that the precipitation-redissolution method using poly(amino acid) has great potential as a concentration method for antibody formulation and medicinal use.

  10. 15th International Conference on Human Antibodies and Hybridomas. 14-16 April 2010, Tiara Park Atlantico Hotel, Porto, Portugal.

    PubMed

    Kotlan, Beatrix

    2010-11-01

    Antibodies and antibody conjugates are currently one of the largest classes of new drug entities under development. These versatile molecules are being investigated for the treatment of many pathological conditions, such as cancer and infectious, inflammatory and autoimmune diseases. Antibodies can exert biological effects as naked antibodies by themselves, or can be used as delivery agents conjugated with various drugs (e.g., immunoconjugates) and as tools of multistep targeting. Site-specific delivery of therapeutic agents has been the ultimate goal of the pharmaceutical industry, as it has the potential to maximize drug efficiency while minimizing side effects. Antibodies have much potential for this objective. Thus, it is useful to summarize some of the main strategies currently being employed for the development of these diverse therapeutic molecules and to highlight the recent novelties in the field. These goals were the focus of the 15th International Conference on Human Antibodies and Hybridomas, held during 14-16 April 2010 in Porto, Portugal.

  11. Response of a Concentrated Monoclonal Antibody Formulation to High Shear

    PubMed Central

    Bee, Jared S.; Stevenson, Jennifer L.; Mehta, Bhavya; Svitel, Juraj; Pollastrini, Joey; Platz, Robert; Freund, Erwin; Carpenter, John F.

    2009-01-01

    There is concern that shear could cause protein unfolding or aggregation during commercial biopharmaceutical production. In this work we exposed two concentrated immunoglobulin-G1 (IgG1) monoclonal antibody (mAb, at >100 mg/mL) formulations to shear rates of between 20,000 and 250,000 s-1 for between 5 minutes and 30 ms using a parallel-plate and capillary rheometer respectively. The maximum shear and force exposures were far in excess of those expected during normal processing operations (20,000 s-1 and 0.06 pN respectively). We used multiple characterization techniques to determine if there was any detectable aggregation. We found that shear alone did not cause aggregation, but that prolonged exposure to shear in the stainless steel parallel-plate rheometer caused a very minor reversible aggregation (<0.3%). Additionally, shear did not alter aggregate populations in formulations containing 17% preformed heat-induced aggregates of a mAb. We calculate that that the forces applied to a protein by production shear exposures (<0.06 pN) are small when compared with the 140 pN force expected at the air-water interface or the 20 to 150 pN forces required to mechanically unfold proteins described in the atomic force microscope (AFM) literature. Therefore, we suggest that in many cases air-bubble entrainment, adsorption to solid surfaces (with possible shear synergy), contamination by particulates, or pump cavitation stresses could be much more important causes of aggregation than shear exposure during production. PMID:19370772

  12. Repeated Acetylcholine Receptor Antibody-Concentrations and Association to Clinical Myasthenia Gravis Development

    PubMed Central

    Heldal, Anne Taraldsen; Eide, Geir Egil; Romi, Fredrik; Owe, Jone Furlund; Gilhus, Nils Erik

    2014-01-01

    Introduction We aimed to examine the longitudinal association between Myasthenia Gravis (MG) clinical severity and concentration of acetylcholine receptor (AChR)-antibodies to evaluate if AChR-antibody variations correlate to disease severity. A positive AChR-antibody test is specific for MG. Material and Methods All patients from western Norway who had two or more AChR- antibody tests in the period 1983–2013 were identified. The Myasthenia Gravis Foundation of America (MGFA) Clinical Classification was used to grade disease development. Multiple ordinal logistic regression analysis was used to estimate a possible predictive effect for AChR-antibody concentration on MGFA classification result. Results In 67 patients two or more AChR-antibody tests with a corresponding MGFA-score were performed, with a total of 309 tests. 56 patients were treated with immunosuppressive drugs and 11 by pyridostigmine only. There was a positive association between concentration of AChR-antibodies and longitudinal MGFA-score for the subgroup with immunosuppressive treatment, but not for those treated with pyridostigmine only. This association between AChR-antibody concentration and MGFA score declined with increasing time since onset (p = 0.005 for the interaction of group×time×concentration). Conclusions For MG patients with immunosuppressive treatment, repeated AChR-antibody measurements give information about clinical development, and can therefore be of support in therapeutic decisions. PMID:25464006

  13. The relationship between concentration of specific antibody at birth and subsequent response to primary immunization.

    PubMed

    Jones, Christine; Pollock, Louisa; Barnett, Sara M; Battersby, Anna; Kampmann, Beate

    2014-02-12

    Trans-placentally acquired antibodies can protect infants from infection in the first months of life. However, high concentrations of antibody at birth may impact the infant's own immune response to primary immunization. We examine the relationship between concentration of specific antibody to Bordetella pertussis, Haemophilus influenzae type b (Hib), tetanus toxoid and pneumococcal antigens at birth and following primary immunization. Healthy mother-infant pairs were recruited from a UK maternity unit. Peripheral blood samples were obtained at birth and 4 weeks after primary immunization. Specific antibody concentrations were determined using enzyme-linked immunosorbent assays. Pertussis antibody concentrations >50 IU/ml, Tetanus antibody levels >0.1 IU/ml and Hib antibody levels >0.15 mg/l were regarded as protective. Following primary immunization, 35/36 (97%) infants had specific antibody concentrations associated with protection against Hib, 32/36 (89%) against pertussis and 36/36 (100%) against tetanus. Concentrations of all specific antibodies were significantly higher than at birth (p<0.0001), except anti-tetanus toxoid, p=0.41. However, there was an inverse correlation between infant antibody concentration at birth and fold-increase in antibody concentration post-immunization for tetanus: rs -0.86 (95%CI -0.93 to -0.74), p<0.0001; pneumococcus: rs -0.82 (95% CI -0.91 to -0.67), p<0.0001; pertussis: rs -0.77 (95% CI -0.89 to -0.58), p<0.0001 and Hib: rs -0.66 (95%CI -0.82 to -0.42), p<0.0001. The highest concentrations of specific IgG at birth were associated with lower concentrations post-immunization for tetanus (p=0.009) and pneumococcus (p=0.03). This association was not observed for Hib (p=0.88) or pertussis (p=0.14). Higher antibody concentration at birth appeared to inhibit the response to infant immunization for tetanus and pneumococcus; the effect was less marked for Hib and pertussis. However, the majority of infants achieved high antibody levels

  14. Combined active and passive immunization against nicotine: minimizing monoclonal antibody requirements using a target antibody concentration strategy.

    PubMed

    Cornish, Katherine E; Harris, Andrew C; LeSage, Mark G; Keyler, Dan E; Burroughs, Danielle; Earley, Cathy; Pentel, Paul R

    2011-11-01

    Nicotine vaccines have shown preliminary evidence of efficacy for enhancing smoking cessation rates, but the serum nicotine-specific antibody (NicAb) concentrations produced are highly variable and many subjects do not develop effective levels. As an alternative to vaccination, passive immunization with nicotine-specific monoclonal antibodies could produce more uniform serum NicAb concentrations, but its use is limited by their high cost and shorter elimination half-life. This study investigated supplementing vaccination with monoclonal antibodies in a targeted fashion to increase vaccine efficacy while minimizing the required monoclonal antibody dose. Rats were vaccinated and then given individualized supplemental doses of the nicotine-specific monoclonal antibody Nic311 to achieve a target total serum NicAb concentration known to be effective for blocking locomotor sensitization (LMS) to nicotine. Rats received vaccine, Nic311, both, or neither, followed by 0.3 mg/kg nicotine s.c. for 10 days to produce LMS. Combination immunotherapy completely blocked the development of LMS, while monotherapy with vaccine or Nic311 alone was only minimally effective. Lower brain nicotine levels were associated with reduced locomotor activity averaged over days 7-10. Despite its greater efficacy, combination immunotherapy did not reduce the variability in the resulting total serum NicAb concentrations. Variability in total serum NicAb concentrations was contributed to by both vaccine-generated antibody and by Nic311. These data show that combination immunotherapy, using a Nic311 dose that is by itself only minimally effective, can substantially enhance nicotine vaccine efficacy. However, variability in serum NicAb levels with combination immunotherapy may make translation of this approach challenging.

  15. Pseudocatalytic Antiaggregation Activity of Antibodies: Immunoglobulins can Influence α-Synuclein Aggregation at Substoichiometric Concentrations.

    PubMed

    Breydo, Leonid; Morgan, Dave; Uversky, Vladimir N

    2016-04-01

    Protein aggregation is involved in a variety of diseases. Alteration of the aggregation pathway, either to produce less toxic structures or to increase aggregate clearance, is a promising therapeutic route. Both active and passive immunization has been used for this purpose. However, the mechanism of action of antibodies on protein aggregates is not completely clear especially given poor ability of antibodies to cross blood-brain barrier. Here, we have shown that antibodies can interfere with protein aggregation at substoichiometric concentrations (as low as 1:1000 antibody to protein ratio). This is an indication that antibodies interact with aggregation intermediates in chaperone-like manner altering the aggregation pathways at very low antibody levels. This observation supports earlier suggestions that antibodies can inhibit aggregation by interaction with low abundance aggregation intermediates.

  16. Solar-hydrogen generation and solar concentration (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Chinello, Enrico; Modestino, Miguel A.; Schüttauf, Jan-Willem; Lambelet, David; Delfino, Antonio; Dominé, Didier; Faes, Antonin; Despeisse, Matthieu; Bailat, Julien; Psaltis, Demetri; Fernandez Rivas, David; Ballif, Christophe; Moser, Christophe

    2016-09-01

    We successfully demonstrated and reported the highest solar-to-hydrogen efficiency with crystalline silicon cells and Earth-abundant electrocatalysts under unconcentrated solar radiation. The combination of hetero-junction silicon cells and a 3D printed Platinum/Iridium-Oxide electrolyzer has been proven to work continuously for more than 24 hours in neutral environment, with a stable 13.5% solar-to-fuel efficiency. Since the hydrogen economy is expected to expand to a global scale, we demonstrated the same efficiency with an Earth-abundant electrolyzer based on Nickel in a basic medium. In both cases, electrolyzer and photovoltaic cells have been specifically sized for their characteristic curves to intersect at a stable operating point. This is foreseen to guarantee constant operation over the device lifetime without performance degradation. The next step is to lower the production cost of hydrogen by making use of medium range solar concentration. It permits to limit the photoabsorbing area, shown to be the cost-driver component. We have recently modeled a self-tracking solar concentrator, able to capture sunlight within the acceptance angle range +/-45°, implementing 3 custom lenses. The design allows a fully static device, avoiding the external tracker that was necessary in a previously demonstrated +/-16° angular range concentrator. We will show two self-tracking methods. The first one relies on thermal expansion whereas the second method relies on microfluidics.

  17. Reversible self-association increases the viscosity of a concentrated monoclonal antibody in aqueous solution.

    PubMed

    Liu, Jun; Nguyen, Mary D H; Andya, James D; Shire, Steven J

    2005-09-01

    This study was conducted to investigate the effect of reversible protein self-association on the viscosity of concentrated monoclonal antibody solutions. The viscosities of the monoclonal antibody solutions were measured by either a capillary viscometer or a cone-plate rheometer at different protein concentrations, pH, and ionic strength. Soluble aggregates were determined by size exclusion chromatography, light scattering, and analytical ultracentrifugation. Self-association of protein at high protein concentration was monitored by sedimentation equilibrium analysis using a preparative ultracentrifuge and a microfractionator. The viscosity of one of the monoclonal antibodies investigated is highly dependent on protein concentration, pH, and ionic strength of buffer and charged excipients. This antibody shows the highest viscosity near its pI at low ionic strength conditions. Sedimentation equilibrium analysis suggests that this antibody tends to reversibly self-associate at high protein concentration. The self-association appears to be quite weak and is not detectable by sedimentation velocity and size exclusion chromatography at low protein concentration. There are no significant differences in the amounts of non-dissociable soluble aggregates formed between low viscosity and high viscosity samples. These results suggest that the reversible multivalent self-association of this protein appears to be mediated mainly by electrostatic interactions of charged residues and results in unusually high viscosity of this monoclonal antibody in solution at low ionic strength conditions.

  18. Specific concentration of antilymphocyte antibodies in the serum cryoprecipitates of patients with systemic lupus erythematosus.

    PubMed Central

    Winfield, J B; Winchester, R J; Wernet, P; Kunkel, H G

    1975-01-01

    Antibodies to surface determinants of human lymphocytes, recognized both by cytotoxicity of fluorescent antibody analysis, were shown to be specifically enriched over the serum levels in cryoprecipitates from patients with systemic lupus erythematosus (SLE). The antilymphocyte antibody was shown to be cold reactive and was exclusively IgM. It was distinct from IgM anti-IgG, which was also variably concentrated in the cryoprecipitates. The question whether the antilymphocyte antibodies appear in the cryoprecipitates as complexes because of interaction with surface membrane antigens, or simply because of cold reactive properties, remains to be determined. The possible clinical relevance of the cryoprecipitation of these antibodies in systemic lupus erythematosus is discussed. PMID:1081927

  19. Naturally occurring antibodies/autoantibodies in polyclonal immunoglobulin concentrates.

    PubMed

    Späth, Peter J; Lutz, Hans U

    2012-01-01

    It was a long way from the use of hyperimmune animal sera for the treatment of toxin-producing infections to the production of polyclonal, polyspecific human immunoglobulin preparations and the use of NAbs as therapeutic tools for autoimmune and inflammatory diseases. Some highlights of the development of knowledge in blood fractionation techniques, basic science and clinical wisdom are reviewed in this chapter. Proudly we mention the outstanding contribution of Swiss scientists and clinicians in the development of IVIG as clinical tool for some otherwise untreatable diseases or taking advantage of its low adverse event profile in long-term treatment of other chronic autoimmune and inflammatory diseases. This chapter summarizes some of the characteristics and the effects in humans of NAbs which are present in IgG concentrates. We call attention to the fact that the human data remain, at least in part, incomplete, among others because even with the most efficient large-scale techniques available not more than approximately 50% of the total IgG in plasma can be fractionated into an immunoglobulin G concentrate.

  20. Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years.

    PubMed

    Grandjean, Philippe; Heilmann, Carsten; Weihe, Pal; Nielsen, Flemming; Mogensen, Ulla B; Timmermann, Amalie; Budtz-Jørgensen, Esben

    2017-12-01

    Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth cohort, 275 and 349 participated in clinical examinations and provided blood samples at ages 18 months and 5 years. PFAS concentrations were measured at birth and at the clinical examinations. Using information on duration of breastfeeding, serum-PFAS concentration profiles during infancy were estimated. As outcomes, serum concentrations of antibodies against tetanus and diphtheria vaccines were determined at age 5. Data from a previous cohort born eight years earlier were available for pooled analyses. Pre-natal exposure showed inverse associations with the antibody concentrations five years later, with decreases by up to about 20% for each two-fold higher exposure, while associations for serum concentrations at ages 18 months and 5 years were weaker. Modeling of serum-PFAS concentration showed levels for age 18 months that were similar to those measured. Concentrations estimated for ages 3 and 6 months showed the strongest inverse associations with antibody concentrations at age 5 years, particularly for tetanus. Joint analyses showed statistically significant decreases in tetanus antibody concentrations by 19-29% at age 5 for each doubling of the PFAS exposure in early infancy. These findings support the notion that the developing adaptive immune system is particularly vulnerable to immunotoxicity during infancy. This vulnerability appears to be the greatest during the first 6 months after birth, where PFAS exposures are affected by breast-feeding.

  1. Direct detection of antibody concentration and affinity in human serum using microscale thermophoresis.

    PubMed

    Lippok, Svenja; Seidel, Susanne A I; Duhr, Stefan; Uhland, Kerstin; Holthoff, Hans-Peter; Jenne, Dieter; Braun, Dieter

    2012-04-17

    The direct quantification of both the binding affinity and absolute concentration of disease-related biomarkers in biological fluids is particularly beneficial for differential diagnosis and therapy monitoring. Here, we extend microscale thermophoresis to target immunological questions. Optically generated thermal gradients were used to deplete fluorescently marked antigens in 2- and 10-fold-diluted human serum. We devised and validated an autocompetitive strategy to independently fit the concentration and dissociation constant of autoimmune antibodies against the cardiac β1-adrenergic receptor related to dilated cardiomyopathy. As an artificial antigen, the peptide COR1 was designed to mimic the second extracellular receptor loop. Thermophoresis resolved antibody concentrations from 2 to 200 nM and measured the dissociation constant as 75 nM. The approach quantifies antibody binding in its native serum environment within microliter volumes and without any surface attachments. The simplicity of the mix and probe protocol minimizes systematic errors, making thermophoresis a promising detection method for personalized medicine.

  2. Chemical Structure and Concentration of Intratumor Catabolites Determine Efficacy of Antibody Drug Conjugates

    PubMed Central

    Yu, Shang-Fan; Ma, Yong; Xu, Keyang; Dragovich, Peter S.; Pillow, Thomas H.; Liu, Luna; Del Rosario, Geoffrey; He, Jintang; Pei, Zhonghua; Sadowsky, Jack D.; Erickson, Hans K.; Hop, Cornelis E. C. A.; Khojasteh, S. Cyrus

    2016-01-01

    Despite recent technological advances in quantifying antibody drug conjugate (ADC) species, such as total antibody, conjugated antibody, conjugated drug, and payload drug in circulation, the correlation of their exposures with the efficacy of ADC outcomes in vivo remains challenging. Here, the chemical structures and concentrations of intratumor catabolites were investigated to better understand the drivers of ADC in vivo efficacy. Anti-CD22 disulfide-linked pyrrolobenzodiazepine (PBD-dimer) conjugates containing methyl- and cyclobutyl-substituted disulfide linkers exhibited strong efficacy in a WSU-DLCL2 xenograft mouse model, whereas an ADC derived from a cyclopropyl linker was inactive. Total ADC antibody concentrations and drug-to-antibody ratios (DAR) in circulation were similar between the cyclobutyl-containing ADC and the cyclopropyl-containing ADC; however, the former afforded the release of the PBD-dimer payload in the tumor, but the latter only generated a nonimmolating thiol-containing catabolite that did not bind to DNA. These results suggest that intratumor catabolite analysis rather than systemic pharmacokinetic analysis may be used to better explain and predict ADC in vivo efficacy. These are good examples to demonstrate that the chemical nature and concentration of intratumor catabolites depend on the linker type used for drug conjugation, and the potency of the released drug moiety ultimately determines the ADC in vivo efficacy. PMID:27417182

  3. Selective concentration of IgD class-specific antibodies in human milk.

    PubMed Central

    Litwin, S D; Zehr, B D; Insel, R A

    1990-01-01

    The participation of human IgD class antibody in local immune responses of breast tissue was studied by analysing the sera-to-milk ratios of total IgD, IgM, IgA, IgG isotypes and albumin found in matched samples, and by analysing the sera-to-milk (S/M) ratios of IgD, IgM, IgA, IgG antibodies against Haemophilus influenzae capsular polysaccharide (PRP), phosphorylcholine, tetanus and in some cases diphtheria antigens. The study group consisted of eight women immunized during pregnancy with PRP, and control, unimmunized women. Albumin, and total IgG showed high S/M ratios. IgA had a low S/M ratio as expected, consistent with reports that IgA is locally concentrated. Total IgD and IgM isotype ratio values were intermediate between IgG and IgA suggesting they were selectively concentrated in breast fluids due to local production or transport mechanisms, or both. Ratios for specific antibodies of IgA and IgM isotypes and for total IgA and IgM isotype showed parallel data. Among the IgD antibodies, those specific for PRP and phosphorylcholine suggested a higher degree of selective concentration as compared with tetanus antigen. In the group of unimmunized women, although selective concentration of total IgD was observed, specific antibody studies were inconclusive due to the low milk IgD antibody levels encountered. The results indicate that IgD (and also IgM) may participate in local immune responses of human breast tissues and fluids; possibly influenced by the nature of the antigen, the state of immunization and the hormonal environment (pregnancy). PMID:2357855

  4. Antibody

    MedlinePlus

    An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples ... microorganisms (bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produced when the immune system mistakenly ...

  5. Antibody treatment against pulmonary exposure to abrin confers significantly higher levels of protection than treatment against ricin intoxication.

    PubMed

    Sabo, Tamar; Gal, Yoav; Elhanany, Eitan; Sapoznikov, Anita; Falach, Reut; Mazor, Ohad; Kronman, Chanoch

    2015-09-02

    Abrin, a potent plant-derived toxin bearing strong resemblance to ricin, irreversibly inactivates ribosomes by site-specific depurination, thereby precipitating cessation of protein synthesis in cells. Due to its high availability and ease of preparation, abrin is considered a biological threat, especially in context of bioterror warfare. To date, there is no established therapeutic countermeasure against abrin intoxication. In the present study, we examined the progress of pulmonary abrin intoxication in mice, evaluated the protective effect of antibody-based post-exposure therapy, and compared these findings to those observed for ricin intoxication and therapy. Salient features of abrin intoxication were found to be similar to those of ricin and include massive recruitment of neutrophils to the lungs, high levels of pro-inflammatory markers in the bronchoalveolar lavage fluid and damage of the alveolar-capillary barrier. In contrast, the protective effect of anti-abrin antibody treatment was found to differ significantly from that of anti-ricin treatment. While anti-ricin treatment efficiency was quite limited even at 24h post-exposure (34% protection), administration of polyclonal anti-abrin antibodies even as late as 72h post-exposure, conferred exceedingly high-level protection (>70%). While both anti-toxin antibody treatments caused neutrophil and macrophage levels in the lungs to revert to normal, only anti-abrin treatment brought about a significant decline in the pulmonary levels of the pro-inflammatory cytokine IL-6. The differential ability of the anti-toxin treatments to dampen inflammation caused by the two similar toxins, abrin and ricin, could explain the radically different levels of protection achieved following antibody treatment.

  6. Capture and Concentration of Waterborne Pathogens Using Lectin and Antibody Coupled Magnetic Beads

    SciTech Connect

    Bennett, Alena M.; Ozanich, Rich M.

    2005-01-01

    Capture and Concentration of Waterborne Pathogens Using Lectin and Antibody Coupled Magnetic Beads. ALENA BENNETT (University of Puget Sound, Tacoma, WA, 98416) RICHARD M. OZANICH, JR. (Pacific Northwest National Laboratory, Richland, WA 99352). The primary challenge of the surveillance of natural and introduced biological threats in large water samples is the purification and concentration process. A method for simultaneously capturing many types of biological pathogens is desired. Lectins coupled with magnetic beads were studied due to their ability to bind to the carbohydrates on the surfaces of cells. With lectin coupled beads we attempted to trap Escherichia coli, Bacillus subtilis, and Brevundimonas diminuta. Also E. coli antibody coupled beads were tested for their effectiveness at concentrating E. coli cells. Bench top indirect and direct cell capture methods were studied for both lectins and antibodies. The indirect method was found to be more effective for cell concentration. Experiments are underway to understand the differences in the two approaches and improve the direct capture method for implementation on an online automated system.

  7. The osmotic pressure of highly concentrated monoclonal antibody solutions: effect of solution conditions.

    PubMed

    Binabaji, Elaheh; Rao, Suma; Zydney, Andrew L

    2014-03-01

    The behavior of monoclonal antibodies at high concentrations is important in downstream processing, drug formulation, and drug delivery. The objective of this study was to evaluate the osmotic pressure of a highly purified monoclonal antibody at concentrations up to 250 g/L over a range of pH and ionic strength, and in the presence of specific excipients, using membrane osmometry. Independent measurements of the second virial coefficient were obtained using self-interaction chromatography, and the net protein charge was evaluated using electrophoretic light scattering. The osmotic pressure at pH 5 and low ionic strength was >50 kPa for antibody concentrations above 200 g/L. The second virial coefficients determined from the oncotic pressure (after subtracting the Donnan contribution) were in good qualitative agreement with those determined by self-interaction chromatography. The second virial coefficient decreased with increasing ionic strength and increasing pH due to the reduction in intermolecular electrostatic repulsion. The third virial coefficient was negative under all conditions, suggesting that multi-body interactions in this system are attractive. The virial coefficients were essentially unaffected by addition of sucrose or proline. These results have important implications for the analysis of protein-protein interactions in downstream processing at high protein concentrations.

  8. Pertussis Antibody Concentrations in Infants Born Prematurely to Mothers Vaccinated in Pregnancy.

    PubMed

    Kent, Alison; Ladhani, Shamez N; Andrews, Nick J; Matheson, Mary; England, Anna; Miller, Elizabeth; Heath, Paul T

    2016-07-01

    Maternal antenatal pertussis-containing vaccination is recommended for the prevention of neonatal pertussis, but the ability of maternal vaccination to protect premature infants is unknown. We hypothesized that that infants born prematurely to antenatally vaccinated women would have higher pertussis antibody concentrations than those born to unvaccinated women. Mothers had been offered a combined tetanus, diphtheria, 5-component acellular pertussis, inactivated polio vaccine from 28 weeks' gestation as part of their routine antenatal care. Premature infants of vaccinated and unvaccinated mothers enrolled in a randomized controlled trial of pneumococcal conjugate vaccine schedules had antibody concentrations (pertussis toxin, filamentous hemoagglutinin [FHA], and fimbriae 2 and 3) measured at 2 months (before primary vaccination), 5 months (1 month after primary vaccination), and 12 months of age. Mothers of 31 (19%) of 160 premature infants had received combined tetanus, diphtheria, 5-component acellular pertussis, inactivated polio vaccine in pregnancy. Compared with infants of unvaccinated mothers, those born to vaccinated mothers had significantly higher antibody concentrations at 2 months for all measured vaccine antigens (P < .001). The number of days between maternal vaccination and delivery and immunoglobulin G concentration at 2 months of age was positively correlated for pertussis toxin (P = .011) and FHA (P = .001). After primary immunization, infants of vaccinated mothers had significantly lower antibody concentrations for FHA (P = .003) compared with infants of unvaccinated mothers; these differences had resolved by 12 months of age. Maternal vaccination administered early in the third trimester may provide protection for infants born prematurely. Copyright © 2016 by the American Academy of Pediatrics.

  9. A Hepatitis C Virus Envelope Polymorphism Confers Resistance to Neutralization by Polyclonal Sera and Broadly Neutralizing Monoclonal Antibodies

    PubMed Central

    Wasilewski, Lisa N.; El-Diwany, Ramy; Munshaw, Supriya; Snider, Anna E.; Brady, Jillian K.; Osburn, William O.; Ray, Stuart C.

    2016-01-01

    ABSTRACT Hepatitis C virus (HCV) infection is a global health problem, with millions of chronically infected individuals at risk for cirrhosis and hepatocellular carcinoma. HCV vaccine development is vital in the effort toward disease control and eradication, an undertaking aided by an increased understanding of the mechanisms of resistance to broadly neutralizing antibodies (bNAbs). In this study, we identified HCV codons that vary deep in a phylogenetic tree of HCV sequences and showed that a polymorphism at one of these positions renders Bole1a, a computationally derived, ancestral genotype 1a HCV strain, resistant to neutralization by both polyclonal-HCV-infected plasma and multiple broadly neutralizing monoclonal antibodies with unique binding epitopes. This bNAb resistance mutation reduces replicative fitness, which may explain the persistence of both neutralization-sensitive and neutralization-resistant variants in circulating viral strains. This work identifies an important determinant of bNAb resistance in an ancestral, representative HCV genome, which may inform HCV vaccine development. IMPORTANCE Worldwide, more than 170 million people are infected with hepatitis C virus (HCV), the leading cause of hepatocellular carcinoma and liver transplantation in the United States. Despite recent significant advances in HCV treatment, a vaccine is needed. Control of the HCV pandemic with drug treatment alone is likely to fail due to limited access to treatment, reinfections in high-risk individuals, and the potential for resistance to direct-acting antivirals (DAAs). Broadly neutralizing antibodies (bNAbs) block infection by diverse HCV variants and therefore serve as a useful guide for vaccine development, but our understanding of resistance to bNAbs is incomplete. In this report, we identify a viral polymorphism conferring resistance to neutralization by both polyclonal plasma and broadly neutralizing monoclonal antibodies, which may inform HCV vaccine development

  10. Solubility Challenges in High Concentration Monoclonal Antibody Formulations: Relationship with Amino Acid Sequence and Intermolecular Interactions.

    PubMed

    Pindrus, Mariya; Shire, Steven J; Kelley, Robert F; Demeule, Barthélemy; Wong, Rita; Xu, Yiren; Yadav, Sandeep

    2015-11-02

    The purpose of this work was to elucidate the molecular interactions leading to monoclonal antibody self-association and precipitation and utilize biophysical measurements to predict solubility behavior at high protein concentration. Two monoclonal antibodies (mAb-G and mAb-R) binding to overlapping epitopes were investigated. Precipitation of mAb-G solutions was most prominent at high ionic strength conditions and demonstrated strong dependence on ionic strength, as well as slight dependence on solution pH. At similar conditions no precipitation was observed for mAb-R solutions. Intermolecular interactions (interaction parameter, kD) related well with high concentration solubility behavior of both antibodies. Upon increasing buffer ionic strength, interactions of mAb-R tended to weaken, while those of mAb-G became more attractive. To investigate the role of amino acid sequence on precipitation behavior, mutants were designed by substituting the CDR of mAb-R into the mAb-G framework (GM-1) or deleting two hydrophobic residues in the CDR of mAb-G (GM-2). No precipitation was observed at high ionic strength for either mutant. The molecular interactions of mutants were similar in magnitude to those of mAb-R. The results suggest that presence of hydrophobic groups in the CDR of mAb-G may be responsible for compromising its solubility at high ionic strength conditions since deleting these residues mitigated the solubility issue.

  11. Anti-VSG antibodies induce an increase in Trypanosoma evansi intracellular Ca2+ concentration.

    PubMed

    Mendoza, M; Uzcanga, G L; Pacheco, R; Rojas, H; Carrasquel, L M; García-Marchan, Y; Serrano-Martín, X; Benaím, G; Bubis, J; Mijares, A

    2008-09-01

    Trypanosoma evansi and Trypanosoma vivax have shown a very high immunological cross-reactivity. Anti-T. vivax antibodies were used to monitor changes in the T. evansi intracellular Ca2+ concentration ([Ca2+]i) by fluorometric ratio imaging from single parasites. A short-time exposure of T. evansi parasites to sera from T. vivax-infected bovines induced an increase in [Ca2+]i, which generated their complete lysis. The parasite [Ca2+]i boost was reduced but not eliminated in the absence of extracellular Ca2+ or following serum decomplementation. Decomplemented anti-T. evansi VSG antibodies also produced an increase in the parasite [Ca2+]i, in the presence of extracellular Ca2+. Furthermore, this Ca2+ signal was reduced following blockage with Ni2+ or in the absence of extracellular Ca2+, suggesting that this response was a combination of an influx of Ca2+ throughout membrane channels and a release of this ion from intracellular stores. The observed Ca2+ signal was specific since (i) it was completely eliminated following pre-incubation of the anti-VSG antibodies with the purified soluble VSG, and (ii) affinity-purified anti-VSG antibodies also generated an increase in [Ca2+]i by measurements on single cells or parasite populations. We also showed that an increase of the T. evansi [Ca2+]i by the calcium A-23187 ionophore led to VSG release from the parasite surface. In addition, in vivo immunofluorescence labelling revealed that anti-VSG antibodies induced the formation of raft patches of VSG on the parasite surface. This is the first study to identify a ligand that is coupled to calcium flux in salivarian trypanosomes.

  12. Liquid high concentration IgG1 antibody formulations by precipitation.

    PubMed

    Matheus, Susanne; Friess, Wolfgang; Schwartz, Daniel; Mahler, Hanns-Christian

    2009-09-01

    A manufacturing approach for liquid high concentration antibody formulations based on precipitation and subsequent re-dissolution was investigated. IgG1 antibody solutions were concentrated from 20 to 100 mg/mL by intermediate precipitation, with a recovery exceeding 95%, retention of the native secondary structure and binding activity as well as adequate stability. Quantitative, reproducible precipitation was performed using 1.45 M ammonium sulphate (pH 5.5 and 8.0), 0.67 M sodium citrate (pH 8.0) and 9% (w/v) PEG 4000 (pH 5.5 and 8.0). Scalability was confirmed from 1 to 100 mL. The concentrations achievable in the re-dissolution step were less affected by the re-dissolution medium, but limited by the residual precipitant. Both, improved removal of remaining precipitant liquid and larger precipitation scales were successful in increasing the final protein concentration. SEC and turbidity analysis directly after re-dissolution indicated that similar protein qualities were obtained, independent from the precipitant used. However, increased aggregate formation was observed after short term storage of the precipitated protein particles at either 2-8 degrees C or ambient temperature. An accelerated mechanical and thermal stability program verified comparable stability of the re-dissolved liquid 100 mg/mL formulations produced by intermediate precipitation to a control formulation obtained by standard ultrafiltration.

  13. Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin.

    PubMed

    Huang, Nai-Jia; Pishesha, Novalia; Mukherjee, Jean; Zhang, Sicai; Deshycka, Rhogerry; Sudaryo, Valentino; Dong, Min; Shoemaker, Charles B; Lodish, Harvey F

    2017-09-04

    A short half-life in the circulation limits the application of therapeutics such as single-domain antibodies (VHHs). We utilize red blood cells to prolong the circulatory half-life of VHHs. Here we present VHHs against botulinum neurotoxin A (BoNT/A) on the surface of red blood cells by expressing chimeric proteins of VHHs with Glycophorin A or Kell. Mice whose red blood cells carry the chimeric proteins exhibit resistance to 10,000 times the lethal dose (LD50) of BoNT/A, and transfusion of these red blood cells into naive mice affords protection for up to 28 days. We further utilize an improved CD34+ culture system to engineer human red blood cells that express these chimeric proteins. Mice transfused with these red blood cells are resistant to highly lethal doses of BoNT/A. We demonstrate that engineered red blood cells expressing VHHs can provide prolonged prophylactic protection against bacterial toxins without inducing inhibitory immune responses and illustrates the potentially broad translatability of our strategy for therapeutic applications.The therapeutic use of single-chain antibodies (VHHs) is limited by their short half-life in the circulation. Here the authors engineer mouse and human red blood cells to express VHHs against botulinum neurotoxin A (BoNT/A) on their surface and show that an infusion of these cells into mice confers long lasting protection against a high dose of BoNT/A.

  14. High Throughput Prediction Approach for Monoclonal Antibody Aggregation at High Concentration.

    PubMed

    Zidar, Mitja; Šušterič, Ana; Ravnik, Miha; Kuzman, Drago

    2017-09-01

    Characterization of the monoclonal antibody aggregation process and identification of stability factors that could be used as indicators of aggregation propensity with an emphasis on a large number of samples and low protein material consumption. Differential scanning calorimetry, dynamic light scattering and size exclusion chromatography were used as the main methodological approaches. Conformational stability, colloidal stability and aggregation kinetics were assessed for two different IgG monoclonal antibody (mAbs) subclasses. Aggregation was induced by exposing the mAbs to 55°C for 3 weeks. mAb samples were prepared in different formulations and concentrations from 1 mg/mL to 50 mg/mL. High temperature stress of mAb samples revealed that monoclonal antibodies followed first order aggregation kinetics, which suggests that the rate-limiting step of monomer loss was unimolecular. Conformational stability of mAbs was estimated with denaturation temperature measurements. Colloidal stability was assessed with dynamic interaction parameter k D . The correlation between aggregation kinetics and colloidal and conformational stability factors was evaluated and the dynamic interaction parameter was found to be a promising predictor of aggregation propensity of monoclonal antibodies. The meaning of using an intermolecular interaction parameter for prediction of what is essentially a unimolecular process is also discussed. This work estimates the significance of different predictors of aggregation propensity at high concentrations as a part of a high throughput, low resource screening method and is a contribution towards determining protein aggregation phenomena in actual systems used for the development and production of biopharmaceuticals.

  15. Human recombinant antimannan immunoglobulin G1 antibody confers resistance to hematogenously disseminated candidiasis in mice.

    PubMed

    Zhang, Mason X; Bohlman, M Charlotte; Itatani, Carol; Burton, Dennis R; Parren, Paul W H I; St Jeor, Stephen C; Kozel, Thomas R

    2006-01-01

    Mannan is a major cell wall component found in Candida species. Natural antimannan antibody is present in sera from most normal adults, but its role in host resistance to hematogenously disseminated candidiasis is unknown. The purpose of this study was to develop recombinant human antimannan antibody and to study its protective function. A phage Fab display combinatorial library containing Fab genes from bone marrow lymphocytes was screened with Candida albicans yeast cells and chemically purified mannan. One antimannan Fab, termed M1, was converted to a full-length immunoglobulin G1 antibody, M1g1, and M1g1 was produced in CHO cells. The M1g1 epitope was found in C. albicans serotypes A and B, Candida tropicalis, Candida guilliermondii, Candida glabrata, and Candida parapsilosis. Its expression was active at both 23 degrees C and 37 degrees C and uniform over the cell surface. BALB/c mice passively immunized with M1g1 were more resistant than control mice to a lethal hematogenous infection by C. albicans, as evidenced by extension of survival in an M1g1 dose-dependent manner (P, 0.08 to <0.001) and by reduction in number of infection foci and their size in the kidney. In vitro studies found that M1g1 promoted phagocytosis and phagocytic killing of C. albicans yeast cells by mouse peritoneal macrophages and was required for activation of the mouse complement cascade. Thus, human antimannan antibody may have a protective role in host resistance to systemic candidiasis.

  16. Single-dose live-attenuated Nipah virus vaccines confer complete protection by eliciting antibodies directed against surface glycoproteins

    PubMed Central

    DeBuysscher, Blair L.; Scott, Dana; Marzi, Andrea; Prescott, Joseph; Feldmann, Heinz

    2016-01-01

    Background Nipah virus (NiV), a zoonotic pathogen causing severe respiratory illness and encephalitis in humans, emerged in Malaysia in 1998 with subsequent outbreaks on an almost annual basis since 2001 in parts of the Indian subcontinent. The high case fatality rate, human-to-human transmission, wide-ranging reservoir distribution and lack of licensed intervention options are making NiV a serious regional and potential global public health problem. The objective of this study was to develop a fast-acting, single-dose NiV vaccine that could be implemented in a ring vaccination approach during outbreaks. Methods In this study we have designed new live-attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSV) expressing NiV glycoproteins (G or F) or nucleoprotein (N) and evaluated their protective efficacy in Syrian hamsters, an established NiV animal disease model. We further characterized the humoral immune response to vaccination in hamsters using ELISA and neutralization assays and performed serum transfer studies. Results Vaccination of Syrian hamsters with a single dose of the rVSV vaccine vectors resulted in strong humoral immune responses with neutralizing activities found only in those animals vaccinated with rVSV expressing NiV G or F proteins. Vaccinated animals with neutralizing antibody responses were completely protected from lethal NiV disease, whereas animals vaccinated with rVSV expressing NiV N showed only partial protection. Protection of NiV G or F vaccinated animals was conferred by antibodies, most likely the neutralizing fraction, as demonstrated by serum transfer studies. Protection of N-vaccinated hamsters was not antibody-dependent indicating a role of adaptive cellular responses for protection. Conclusions The rVSV vectors expressing Nipah virus G or F are prime candidates for new ‘emergency vaccines’ to be utilized for NiV outbreak management. PMID:24631094

  17. Higher Plasma Concentration of Food-Specific Antibodies in Persons with Autistic Disorder in Comparison to Their Siblings

    ERIC Educational Resources Information Center

    Trajkovski, Vladimir; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Trajkov, Dejan; Arsov, Todor; Strezova, Ana; Ajdinski, Ljubomir; Spiroski, Mirko

    2008-01-01

    Specific IgA, IgG, and IgE antibodies to food antigens in 35 participants with autistic disorder and 21 of their siblings in the Republic of Macedonia were examined. Statistically significant higher plasma concentration of IgA antibodies against alpha-lactalbumin, beta-lactoglobulin, casein, and gliadin were found in the children with autistic…

  18. Higher Plasma Concentration of Food-Specific Antibodies in Persons with Autistic Disorder in Comparison to Their Siblings

    ERIC Educational Resources Information Center

    Trajkovski, Vladimir; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Trajkov, Dejan; Arsov, Todor; Strezova, Ana; Ajdinski, Ljubomir; Spiroski, Mirko

    2008-01-01

    Specific IgA, IgG, and IgE antibodies to food antigens in 35 participants with autistic disorder and 21 of their siblings in the Republic of Macedonia were examined. Statistically significant higher plasma concentration of IgA antibodies against alpha-lactalbumin, beta-lactoglobulin, casein, and gliadin were found in the children with autistic…

  19. Passive Transfer of Immunoglobulin Y Antibody to Streptococcus mutans Glucan Binding Protein B Can Confer Protection against Experimental Dental Caries

    PubMed Central

    Smith, Daniel J.; King, William F.; Godiska, Ronald

    2001-01-01

    Active immunization with Streptococcus mutans glucan binding protein B (GBP-B) has been shown to induce protection against experimental dental caries. This protection presumably results from continuous secretion of salivary antibody to GBP-B, which inhibits accumulation of S. mutans within the oral biofilm. The purpose of this study was to explore the influence of short-term (9- or 24-day) passive oral administration of antibody to S. mutans GBP-B on the longer-term accumulation and cariogenicity of S. mutans in a rat model of dental caries. Preimmune chicken egg yolk immunoglobulin Y (IgY) or IgY antibody to S. mutans GBP-B was supplied in lower (experiment 1) and higher (experiment 2) concentrations in the diet and drinking water of rats for 9 (experiment 1) or 24 (experiment 2) days. During the first 3 days of IgY feeding, all animals were challenged with 5 × 106 streptomycin-resistant S. mutans strain SJ-r organisms. Rats remained infected with S. mutans for 78 days, during which rat molars were sampled for the accumulation of S. mutans SJ-r bacteria and total streptococci. Geometric mean levels of S. mutans SJ-r accumulation on molar surfaces were significantly lower in antibody-treated rats on days 16 and 78 of experiment 2 and were lower on all but the initial (day 5) swabbing occasions in both experiments. Relative to controls, the extent of molar dental caries measured on day 78 was also significantly decreased. The decrease in molar caries correlated with the amount and duration of antibody administration. This is the first demonstration that passive antibody to S. mutans GBP-B can have a protective effect against cariogenic S. mutans infection and disease. Furthermore, this decrease in infection and disease did not require continuous antibody administration for the duration of the infection period. This study also indicates that antibody to components putatively involved only in cellular aggregation can have a significant effect on the incorporation of

  20. Naturally selected hepatitis C virus polymorphisms confer broad neutralizing antibody resistance

    PubMed Central

    Bailey, Justin R.; Wasilewski, Lisa N.; Snider, Anna E.; El-Diwany, Ramy; Osburn, William O.; Keck, Zhenyong; Foung, Steven K.H.; Ray, Stuart C.

    2014-01-01

    For hepatitis C virus (HCV) and other highly variable viruses, broadly neutralizing mAbs are an important guide for vaccine development. The development of resistance to anti-HCV mAbs is poorly understood, in part due to a lack of neutralization testing against diverse, representative panels of HCV variants. Here, we developed a neutralization panel expressing diverse, naturally occurring HCV envelopes (E1E2s) and used this panel to characterize neutralizing breadth and resistance mechanisms of 18 previously described broadly neutralizing anti-HCV human mAbs. The observed mAb resistance could not be attributed to polymorphisms in E1E2 at known mAb-binding residues. Additionally, hierarchical clustering analysis of neutralization resistance patterns revealed relationships between mAbs that were not predicted by prior epitope mapping, identifying 3 distinct neutralization clusters. Using this clustering analysis and envelope sequence data, we identified polymorphisms in E2 that confer resistance to multiple broadly neutralizing mAbs. These polymorphisms, which are not at mAb contact residues, also conferred resistance to neutralization by plasma from HCV-infected subjects. Together, our method of neutralization clustering with sequence analysis reveals that polymorphisms at noncontact residues may be a major immune evasion mechanism for HCV, facilitating viral persistence and presenting a challenge for HCV vaccine development. PMID:25500884

  1. Treatment with a Monoclonal Antibody against Methamphetamine and Amphetamine Reduces Maternal and Fetal Rat Brain Concentrations in Late Pregnancy

    PubMed Central

    White, Sarah J.; Hendrickson, Howard P.; Atchley, William T.; Laurenzana, Elizabeth M.; Gentry, W. Brooks; Williams, D. Keith; Owens, S. Michael

    2014-01-01

    We hypothesized that treatment of pregnant rat dams with a dual reactive monoclonal antibody (mAb4G9) against (+)-methamphetamine [METH; equilibrium dissociation rate constant (KD) = 16 nM] and (+)-amphetamine (AMP; KD = 102 nM) could confer maternal and fetal protection from brain accumulation of both drugs of abuse. To test this hypothesis, pregnant Sprague-Dawley rats (on gestational day 21) received a 1 mg/kg i.v. METH dose, followed 30 minutes later by vehicle or mAb4G9 treatment. The mAb4G9 dose was 0.56 mole-equivalent in binding sites to the METH body burden. Pharmacokinetic analysis showed baseline METH and AMP elimination half-lives were congruent in dams and fetuses, but the METH volume of distribution in dams was nearly double the fetal values. The METH and AMP area under the serum concentration-versus-time curves from 40 minutes to 5 hours after mAb4G9 treatment increased >7000% and 2000%, respectively, in dams. Fetal METH serum did not change, but AMP decreased 23%. The increased METH and AMP concentrations in maternal serum resulted from significant increases in mAb4G9 binding. Protein binding changed from ∼15% to > 90% for METH and AMP. Fetal serum protein binding appeared to gradually increase, but the absolute fraction bound was trivial compared with the dams. mAb4G9 treatment significantly reduced METH and AMP brain values by 66% and 45% in dams and 44% and 46% in fetuses (P < 0.05), respectively. These results show anti-METH/AMP mAb4G9 therapy in dams can offer maternal and fetal brain protection from the potentially harmful effects of METH and AMP. PMID:24839971

  2. Treatment with a monoclonal antibody against methamphetamine and amphetamine reduces maternal and fetal rat brain concentrations in late pregnancy.

    PubMed

    White, Sarah J; Hendrickson, Howard P; Atchley, William T; Laurenzana, Elizabeth M; Gentry, W Brooks; Williams, D Keith; Owens, S Michael

    2014-08-01

    We hypothesized that treatment of pregnant rat dams with a dual reactive monoclonal antibody (mAb4G9) against (+)-methamphetamine [METH; equilibrium dissociation rate constant (KD) = 16 nM] and (+)-amphetamine (AMP; KD = 102 nM) could confer maternal and fetal protection from brain accumulation of both drugs of abuse. To test this hypothesis, pregnant Sprague-Dawley rats (on gestational day 21) received a 1 mg/kg i.v. METH dose, followed 30 minutes later by vehicle or mAb4G9 treatment. The mAb4G9 dose was 0.56 mole-equivalent in binding sites to the METH body burden. Pharmacokinetic analysis showed baseline METH and AMP elimination half-lives were congruent in dams and fetuses, but the METH volume of distribution in dams was nearly double the fetal values. The METH and AMP area under the serum concentration-versus-time curves from 40 minutes to 5 hours after mAb4G9 treatment increased >7000% and 2000%, respectively, in dams. Fetal METH serum did not change, but AMP decreased 23%. The increased METH and AMP concentrations in maternal serum resulted from significant increases in mAb4G9 binding. Protein binding changed from ∼15% to > 90% for METH and AMP. Fetal serum protein binding appeared to gradually increase, but the absolute fraction bound was trivial compared with the dams. mAb4G9 treatment significantly reduced METH and AMP brain values by 66% and 45% in dams and 44% and 46% in fetuses (P < 0.05), respectively. These results show anti-METH/AMP mAb4G9 therapy in dams can offer maternal and fetal brain protection from the potentially harmful effects of METH and AMP. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Concentrations of antibodies against β-amyloid 40/42 monomer and oligomers in Chinese intravenous immunoglobulins.

    PubMed

    Ye, Shengliang; Zeng, Renyong; Jiang, Peng; Hou, Mingxia; Liu, Fengjuan; Wang, Zongkui; Du, Xi; Yuan, Jing; Chen, Yunhua; Cao, Haijun; Ma, Li; Li, Changqing

    2017-02-17

    Intravenous immunoglobulin (IVIg) preparations are being investigated as a potential agent for treatment or prevention of Alzheimer's disease (AD). Antibodies towards soluble β-amyloid (Aβ) contained in IVIg were considered to be the major component contributing to the beneficial effect of the preparations in pilot studies. This study compared the antibody concentrations against Aβ in Octagam(®) IVIg (Octapharma) and 9 IVIg preparations from different Chinese manufacturers by ELISA, using Aβ40 monomer, Aβ40 soluble oligomers, Aβ42 monomer and Aβ42 soluble oligomers as the antigens. The results showed that each preparation contained different antibody levels against the four Aβ forms. The median values of the four antibody concentrations in Chinese IVIg preparations were 16.53, 8.47, 24.36 and 33.25μg/mL, which were remarkably higher than that in Octagam(®) IVIg (1.66, 2.07, 4.61 and 4.64μg/mL). Moreover, the anti-Aβ42 oligomer antibody levels in almost all IVIg preparations were higher than the anti-Aβ42 monomer antibody, and the concentrations of anti-Aβ42 antibodies in most of the IVIg preparations were significantly higher than that of anti-Aβ40 antibodies. These findings will contribute to an increased understanding of the uniqueness of Chinese IVIg preparations, and could provide support for a trial of a Chinese IVIg product in AD patients.

  4. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease

    PubMed Central

    Vande Casteele, Niels; Khanna, Reena; Levesque, Barrett G; Stitt, Larry; Zou, G Y; Singh, Sharat; Lockton, Steve; Hauenstein, Scott; Ohrmund, Linda; Greenberg, Gordon R; Rutgeerts, Paul J; Gils, Ann; Sandborn, William J; Vermeire, Séverine; Feagan, Brian G

    2015-01-01

    Objective Although low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients with adequate infliximab concentrations is uncertain. We evaluated this question using an assay sensitive for identification of ATI in the presence of infliximab. Design In an observational study, 1487 trough serum samples from 483 patients with CD who participated in four clinical studies of maintenance infliximab therapy were analysed using a fluid phase mobility shift assay. Infliximab and ATI concentrations most discriminant for remission, defined as a C-reactive protein concentration of ≤5 mg/L, were determined by receiver operating characteristic curves. A multivariable regression model evaluated these factors as independent predictors of remission. Results Based upon analysis of 1487 samples, 77.1% of patients had detectable and 22.9% had undetectable infliximab concentrations, of which 9.5% and 71.8%, respectively, were positive for ATI. An infliximab concentration of >2.79 μg/mL (area under the curve (AUC)=0.681; 95% CI 0.632 to 0.731) and ATI concentration of <3.15 U/mL (AUC=0.632; 95% CI 0.589 to 0.676) were associated with remission. Multivariable analysis showed that concentrations of both infliximab trough (OR 1.8; 95% CI 1.3 to 2.5; p<0.001) and ATI (OR 0.57; 95% CI 0.39 to 0.81; p=0.002) were independent predictors of remission. Conclusions The development of ATI increases the probability of active disease even at low concentrations and in the presence of a therapeutic concentration of drug during infliximab maintenance therapy. Evaluation of strategies to prevent ATI formation, including therapeutic drug monitoring with selective infliximab dose intensification, is needed. PMID:25336114

  5. Pasteurized, monoclonal antibody factor VIII concentrate: establishing a new standard for purity and viral safety of plasma-derived concentrates.

    PubMed

    Goldsmith, J C

    2000-03-01

    A factor VIII concentrate (Monoclate-P) manufactured using a combination of pasteurization and immunoaffinity chromatography has been chosen to compare and contrast manufacturing aspects of plasma-derived factor VIII concentrates. Pasteurization is a virucidal method with a long safety record in clinical practice, while immuno-affinity chromatography selectively isolates and purifies the procoagulant protein of factor VIII, and partitions potential viral contaminants and nonessential proteins to the unbound fraction. The complete Monoclate-P production process reduces human immunodeficiency virus by > or = 10.5 log10, Sindbis (a model for hepatitis C virus) by > or = 6.5 log10, and murine encephalomyocarditis virus (a non-enveloped model virus) by 7.1 log10. The viral safety of Monoclate-P has been further demonstrated in clinical studies in patients not previously treated with blood or plasma-derived products. Additionally, the manufacture of Monoclate-P includes careful donor screening and plasma testing for antibodies to syphilis and human immunodeficiency, hepatitis B, and hepatitis C viruses to enhance source plasma safety. Combined with donor selection and plasma testing, multiple viral reduction steps effectively eliminate both lipid-enveloped viruses (e.g. human immunodeficiency, hepatitis B and C) and non-lipid-enveloped viruses (e.g. hepatitis A). In addition, polymerase chain reaction-based nucleic acid detection tests for hepatitis B and C viruses and for human immunodeficiency virus-1 have been introduced as part of an investigational new drug mechanism.

  6. Concentrated polymer brush-modified silica particle coating confers biofouling-resistance on modified materials.

    PubMed

    Yoshikawa, Chiaki; Qiu, Jun; Shimizu, Yoshihisa; Huang, Chih-Feng; Gelling, Onko-Jan; van den Bosch, Edith

    2017-01-01

    Biofouling, an undesired adsorption of biological material to otherwise inert surfaces, is detrimental in medical, pharmaceutical, and other sectors. Concentrated polymer brushes (CPB) confer non-biofouling properties on modified surfaces but are cumbersome to fabricate. Here, a simple and versatile method of fabricating non-biofouling coatings for various substrates was developed using CPB-modified silica nanoparticles (SiPs). Concentrated poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) brushes were grafted on SiPs by surface-initiated atom transfer radical polymerization. CPB-SiPs were spin-coated onto silicon wafers or quartz crystal microbalance (QCM) sensor chips with phenyl azido cross-linkers. SiP cross-linking was then performed by ultra violet irradiation for 20s, or by heating at 120°C for 12h. Protein adsorption to coatings was studied by QCM approach and human umbilical vein endothelial cell adhesion to coatings was examined. SiP to cross-linker weight ratios were varied from 2.0/0.5 to 9.0/0.5 (wt/wt%) and the coatings almost completely suppressed protein adsorption and cell adhesion to treated surfaces. The coating was also applied to polymeric films, rendering these materials biofouling-resistant.

  7. Observation of small cluster formation in concentrated monoclonal antibody solutions and its implications to solution viscosity.

    PubMed

    Yearley, Eric J; Godfrin, Paul D; Perevozchikova, Tatiana; Zhang, Hailiang; Falus, Peter; Porcar, Lionel; Nagao, Michihiro; Curtis, Joseph E; Gawande, Pradad; Taing, Rosalynn; Zarraga, Isidro E; Wagner, Norman J; Liu, Yun

    2014-04-15

    Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable mAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions.

  8. Smartphone dongle for simultaneous measurement of hemoglobin concentration and detection of HIV antibodies.

    PubMed

    Guo, Tiffany; Patnaik, Ritish; Kuhlmann, Kevin; Rai, Alex J; Sia, Samuel K

    2015-09-07

    It is traditionally difficult to incorporate two classes of diagnostic tests into a single platform. In this work, we demonstrate a microfluidic-based smartphone dongle that simultaneously measures concentration of hemoglobin and detects HIV antibodies. Specifically, we demonstrate how a previously published immunoassay device, which measured optical density of silver precipitation on gold colloids, can be expanded to quantitatively measure hemoglobin concentration via a colorimetric assay. By lysing whole blood components with CHAPS detergent, we achieved highly reproducible measurement of hemoglobin concentration with the device. We tested this dual test on 38 patient samples from Columbia University Medical Center. Compared with the Hemocue Hb 201+ analyzer, hemoglobin concentrations from our device were accurate within 1.2 g dL(-1), while the HIV immunoassay (in the presence of CHAPS detergent) showed 95% sensitivity and 95% specificity, comparable to our previous studies. This work demonstrates the feasibility of integrating two classes of diagnostic tests (a colorimetric-based quantitative measurement and an immunoassay based on silver precipitation on gold colloids) into a low-cost, fast, and low-power dongle that works with smartphones, and creates a novel dual panel with clinical utility for antenatal-care settings.

  9. Do Clustering Monoclonal Antibody Solutions Really Have a Concentration Dependence of Viscosity?

    PubMed Central

    Pathak, Jai A.; Sologuren, Rumi R.; Narwal, Rojaramani

    2013-01-01

    Protein solution rheology data in the biophysics literature have incompletely identified factors that govern hydrodynamics. Whereas spontaneous protein adsorption at the air/water (A/W) interface increases the apparent viscosity of surfactant-free globular protein solutions, it is demonstrated here that irreversible clusters also increase system viscosity in the zero shear limit. Solution rheology measured with double gap geometry in a stress-controlled rheometer on a surfactant-free Immunoglobulin solution demonstrated that both irreversible clusters and the A/W interface increased the apparent low shear rate viscosity. Interfacial shear rheology data showed that the A/W interface yields, i.e., shows solid-like behavior. The A/W interface contribution was smaller, yet nonnegligible, in double gap compared to cone-plate geometry. Apparent nonmonotonic composition dependence of viscosity at low shear rates due to irreversible (nonequilibrium) clusters was resolved by filtration to recover a monotonically increasing viscosity-concentration curve, as expected. Although smaller equilibrium clusters also existed, their size and effective volume fraction were unaffected by filtration, rendering their contribution to viscosity invariant. Surfactant-free antibody systems containing clusters have complex hydrodynamic response, reflecting distinct bulk and interface-adsorbed protein as well as irreversible cluster contributions. Literature models for solution viscosity lack the appropriate physics to describe the bulk shear viscosity of unstable surfactant-free antibody solutions. PMID:23442970

  10. The usage of phage mini-antibodies as a means of detecting ferritin concentration in animal blood serum.

    PubMed

    Staroverov, Sergey A; Volkov, Alexei A; Fomin, Alexander S; Laskavuy, Vladislav N; Mezhennyy, Pavel V; Kozlov, Sergey V; Larionov, Sergey V; Fedorov, Michael V; Dykman, Lev A; Guliy, Olga I

    2015-01-01

    Mini-antibodies that have specific ferritin response have been produced for the first time using sheep's phage libraries (Griffin.1, Medical Research Council, Cambridge, UK). Produced phage antibodies were used for the first time for the development of diagnostic test kits for ferritin detection in the blood of cattle. The immunodot assay with secondary biospecific labeling is suggested as means of ferritin detection in cow blood serum (antiferritin phage antibodies and rabbit antiphage antibodies conjugated with different labels). Сolloidal gold, gold nanoshells, and horse reddish peroxidase used as labels have shown a similar response while detecting concentration of ferritin (0.2 mg/mL). It is shown that the method of solid-phase immunoassay with a visual view of the results allows determination of the minimum concentration of ferritin in the blood of cows at 0.225 g/mL.

  11. Vaccination schedules to raise antibody concentrations against epsilon-toxin of Clostridium perfringens in ewes and their triplet lambs.

    PubMed

    de la Rosa, C; Hogue, D E; Thonney, M L

    1997-09-01

    The objective of this experiment was to compare vaccination schedules for ewes and their lambs to raise antibody concentrations to epsilon-toxin of Clostridium perfringens, the causative agent of enterotoxemia. Half of 200 Finnsheep x Dorset ewes were vaccinated with C. perfringens type D toxoid vaccine 3 wk before lambing. Serum samples were obtained from 20 ewes that were to be vaccinated and 20 ewes that would remain unvaccinated before treatment and at wk 2, 1, and 0 before the start of lambing. Antibody concentrations in sera of unvaccinated ewes remained at 2 IU/mL, but they peaked in vaccinated ewes at 15 IU/mL by wk 1 before lambing. Lambs from each of the first 13 and the first 14 sets of triplets from vaccinated and unvaccinated ewes, respectively, received one of three vaccination treatments: no vaccine (control), vaccination on d 1 and 21 of age, or vaccination on d 21 and 42 of age. Antibody concentrations declined in sera of vaccinated ewes from 8.5 IU/mL immediately after lambing to 3 IU/mL 12 wk later. Vaccination of lambs did not increase sera antibody concentration. However, prepartum vaccination of ewes significantly increased lamb antibody concentrations (19 IU/mL) compared with lambs reared by unvaccinated ewes (2 IU/mL). Vaccination of ewes resulted in lambs with higher antibody concentrations until wk 10 postpartum. Concentrations declined to .6 IU/mL in all lambs at 12 wk. Because concentrations of .2 IU/mL may be protective, these results indicate that vaccination of ewes before lambing imparts passive protection in lambs to 12 wk of age, whereas vaccination of young lambs provides no added protection.

  12. Sex differences in the early life correlates of natural antibody concentrations.

    PubMed

    Palmer, A C; Schulze, K J; Khatry, S K; De Luca, L M; West, K P

    2015-12-01

    Innate-like B1a lymphocytes arise from long-lived progenitors produced exclusively by fetal stem cells. Any insults coinciding with this early lymphopoietic wave could have a permanent impact on the B1a population and its unique protein products, the natural antibodies (NAb). We investigated early life nutritional influences on NAb concentrations of pre-adolescent children (n=290) in rural Nepal for whom we had extensive information on exposures from pregnancy and early infancy. Infant size and growth were strongly associated with NAb concentrations at 9-13 years of age among males (e.g., for neonatal weight: βBOYS=0.43; P<0.001), but not females (e.g., for neonatal weight: βGIRLS=-0.16; P=0.26). In females, season of birth was associated with NAb concentrations, with marked reductions among girls born during the pre-monsoon (March-May; βGIRLS=-0.39; P=0.01) and pre-harvest (September-November; βGIRLS=-0.35; P=0.03) seasons. Our findings suggest that nutritional or other environmental influences on immune development may vary by sex, with potential consequences for immune function during infancy and long-term risk of immune-mediated disease.

  13. The enhancement of antibody concentration and achievement of high cell density CHO cell cultivation by adding nucleoside.

    PubMed

    Takagi, Yasuhiro; Kikuchi, Takuya; Wada, Ryuta; Omasa, Takeshi

    2017-03-02

    Recently, with the dramatic increase in demand for therapeutic antibodies, Chinese hamster ovary (CHO) cell culture systems have made significant progress in recombinant antibody production. Over the past two decades, recombinant antibody productivity has been improved by more than 100-fold. Medium optimization has been identified as an important key approach for increasing product concentrations. In this study, we evaluated the effects of deoxyuridine addition to fed-batch cultures of antibody-expressing CHO cell lines. Furthermore, we investigated the effects of combined addition of deoxyuridine, thymidine, and deoxycytidine. Our results suggest that addition of these pyrimidine nucleosides can increase CHO cell growth, with no significant change in the specific production rate. As a result of the increased cell growth, the antibody concentration was elevated and we were able to achieve more than 9 g/L during 16 days of culture. Similar effects of nucleoside addition were observed in fed-batch cultures of a Fab fragment-expressing CHO cell line, and the final Fab fragment concentration was more than 4 g/L. This nucleoside addition strategy could be a powerful platform for efficient antibody production.

  14. Multi‐criteria manufacturability indices for ranking high‐concentration monoclonal antibody formulations

    PubMed Central

    Velayudhan, Ajoy; Thornhill, Nina F.

    2017-01-01

    ABSTRACT The need for high‐concentration formulations for subcutaneous delivery of therapeutic monoclonal antibodies (mAbs) can present manufacturability challenges for the final ultrafiltration/diafiltration (UF/DF) step. Viscosity levels and the propensity to aggregate are key considerations for high‐concentration formulations. This work presents novel frameworks for deriving a set of manufacturability indices related to viscosity and thermostability to rank high‐concentration mAb formulation conditions in terms of their ease of manufacture. This is illustrated by analyzing published high‐throughput biophysical screening data that explores the influence of different formulation conditions (pH, ions, and excipients) on the solution viscosity and product thermostability. A decision tree classification method, CART (Classification and Regression Tree) is used to identify the critical formulation conditions that influence the viscosity and thermostability. In this work, three different multi‐criteria data analysis frameworks were investigated to derive manufacturability indices from analysis of the stress maps and the process conditions experienced in the final UF/DF step. Polynomial regression techniques were used to transform the experimental data into a set of stress maps that show viscosity and thermostability as functions of the formulation conditions. A mathematical filtrate flux model was used to capture the time profiles of protein concentration and flux decay behavior during UF/DF. Multi‐criteria decision‐making analysis was used to identify the optimal formulation conditions that minimize the potential for both viscosity and aggregation issues during UF/DF. Biotechnol. Bioeng. 2017;114: 2043–2056. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Perodicals, Inc. PMID:28464235

  15. Analysis of Antibody Aggregate Content at Extremely High Concentrations Using Sedimentation Velocity with a Novel Interference Optics

    PubMed Central

    Schilling, Kristian; Krause, Frank

    2015-01-01

    Monoclonal antibodies represent the most important group of protein-based biopharmaceuticals. During formulation, manufacturing, or storage, antibodies may suffer post-translational modifications altering their physical and chemical properties. Such induced conformational changes may lead to the formation of aggregates, which can not only reduce their efficiency but also be immunogenic. Therefore, it is essential to monitor the amount of size variants to ensure consistency and quality of pharmaceutical antibodies. In many cases, antibodies are formulated at very high concentrations > 50 g/L, mostly along with high amounts of sugar-based excipients. As a consequence, all routine aggregation analysis methods, such as size-exclusion chromatography, cannot monitor the size distribution at those original conditions, but only after dilution and usually under completely different solvent conditions. In contrast, sedimentation velocity (SV) allows to analyze samples directly in the product formulation, both with limited sample-matrix interactions and minimal dilution. One prerequisite for the analysis of highly concentrated samples is the detection of steep concentration gradients with sufficient resolution: Commercially available ultracentrifuges are not able to resolve such steep interference profiles. With the development of our Advanced Interference Detection Array (AIDA), it has become possible to register interferograms of solutions as highly concentrated as 150 g/L. The other major difficulty encountered at high protein concentrations is the pronounced non-ideal sedimentation behavior resulting from repulsive intermolecular interactions, for which a comprehensive theoretical modelling has not yet been achieved. Here, we report the first SV analysis of highly concentrated antibodies up to 147 g/L employing the unique AIDA ultracentrifuge. By developing a consistent experimental design and data fit approach, we were able to provide a reliable estimation of the minimum

  16. Opalescence in monoclonal antibody solutions and its correlation with intermolecular interactions in dilute and concentrated solutions.

    PubMed

    Raut, Ashlesha S; Kalonia, Devendra S

    2015-04-01

    Opalescence indicates physical instability of a formulation because of the presence of aggregates or liquid-liquid phase separation in solution and has been reported for monoclonal antibody (mAb) formulations. Increased solution opalescence can be attributed to attractive protein-protein interactions (PPIs). Techniques including light scattering, AUC, or membrane osmometry are routinely employed to measure PPIs in dilute solutions, whereas opalescence is seen at relatively higher concentrations, where both long- and short-range forces contribute to overall PPIs. The mAb molecule studied here shows a unique property of high opalescence because of liquid-liquid phase separation. In this study, opalescence measurements are correlated to PPIs measured in diluted and concentrated solutions using light scattering (kD ) and high-frequency rheology (G'), respectively. Charges on the molecules were calculated using zeta potential measurements. Results indicate that high opalescence and phase separation are a result of the attractive interactions in solution; however, the presence of attractive interactions do not always imply phase separation. Temperature dependence of opalescence suggests that thermodynamic contribution to opalescence is significant and Tcloud can be utilized as a potential tool to assess attractive interactions in solution.

  17. Liquid-liquid phase separation of a monoclonal antibody at low ionic strength: Influence of anion charge and concentration.

    PubMed

    Reiche, Katharina; Hartl, Josef; Blume, Alfred; Garidel, Patrick

    2017-01-01

    Liquid-liquid phase separation (LLPS) of a monoclonal antibody solution was investigated at low ionic strength in the presence of oligovalent anions, such as citrate, trimellitate, pyromellitate and mellitate. Phase separation was observed at the isoelectric point of the antibody at pH8.7 as well as in more acidic pH regions in the presence of the tested oligovalent ions. This can be attributed to charge neutralization via binding of the oligovalent anions to the positively charged antibody. The influence of the anion concentration on liquid-liquid phase separation with respect to the net charge of the antibody was examined. Similarities to the formation of a complex coacervate were shown to apply. These findings enable us to understand the usage of excipients to rationally induce or avoid liquid-liquid phase separation at low ionic strength. Furthermore we present a method to directly examine the competition of different ions for the solvation shell, called buffer equilibration.

  18. Surface Plasmon Resonance (SPR) Detection Using Antibody-Linked Magnetic Nanoparticles for Analyte Capture, Purification, Concentration and Signal Amplification

    PubMed Central

    Soelberg, Scott D.; Stevens, Richard C.; Limaye, Ajit P.; Furlong, Clement E.

    2009-01-01

    Rapid, sensitive and accurate detection of analytes present in low concentrations in complex matrices is a critical challenge. One issue that affects many biosensor protocols is the number and nature of the interferents present in complex matrices such as plasma, urine, stool and environmental samples, resulting in loss of sensitivity and specificity. We have developed a method for rapid purification, concentration and detection of target analytes from complex matrices using antibody-coated superparamagnetic nanobeads (immunomagnetic beads, or IMBs). The SPR detection signal from Staphylococcal enterotoxin B (SEB) was dramatically increased when the IMBs were used as detection amplifiers. When SEB detection included a 10-fold concentration/purification IMB protocol, a substantial increase in detection sensitivity was observed. This procedure was used to successfully purify and concentrate SEB from serum and stool samples, then amplify the SPR detection signal. SEB at a concentration of 100 picograms/mL was easily detected in both buffer and stool samples using this procedure. The IMB protocol also served to verify the analyte detection by using two different anti-SEB antibodies, mouse monoclonal antibodies attached to the magnetic nanobeads and rabbit polyclonal antibodies on the SPR sensor surface. Multiple detections of SEB in stool were performed using the same sensor surface by regenerating the sensor surfaces with a pH 2.2 buffer wash. PMID:19215065

  19. Surface plasmon resonance detection using antibody-linked magnetic nanoparticles for analyte capture, purification, concentration, and signal amplification.

    PubMed

    Soelberg, Scott D; Stevens, Richard C; Limaye, Ajit P; Furlong, Clement E

    2009-03-15

    Rapid, sensitive, and accurate detection of analytes present in low concentrations in complex matrixes is a critical challenge. One issue that affects many biosensor protocols is the number and nature of the interferences present in complex matrixes such as plasma, urine, stool, and environmental samples, resulting in loss of sensitivity and specificity. We have developed a method for rapid purification, concentration, and detection of target analytes from complex matrixes using antibody-coated superparamagnetic nanobeads (immunomagnetic beads, or IMBs). The surface plasmon resonance (SPR) detection signal from staphylococcal enterotoxin B (SEB) was dramatically increased when the IMBs were used as detection amplifiers. When SEB detection included a 10-fold concentration/purification IMB protocol, a substantial increase in detection sensitivity was observed. This procedure was used to successfully purify and concentrate SEB from serum and stool samples, then amplify the SPR detection signal. SEB at a concentration of 100 pg/mL was easily detected in both buffer and stool samples using this procedure. The IMB protocol also served to verify the analyte detection by using two different anti-SEB antibodies, mouse monoclonal antibodies attached to the magnetic nanobeads and rabbit polyclonal antibodies on the SPR sensor surface. Multiple detections of SEB in stool were performed using the same sensor surface by regenerating the sensor surfaces with a pH 2.2 buffer wash.

  20. Association between serum pepsinogen A and C levels, serum gastrin concentrations and Helicobacter pylori antibodies.

    PubMed

    Kullich, W; Pöllmann, G; Czerwenka, C; Klein, G

    1999-01-01

    Pepsinogen A and C as well as gastrin were measured in the serum of 117 patients with rheumatic diseases. Moreover, the patients were divided up in groups by aids of a semiquantitative, rapid enzyme immunoassay for detection of Helicobacter pylori: 20 patients without H. pylori antibodies (AB) negative, 18 positive + (= weak AB-titre), 21 positive +2 (medium AB-titre), and 58 positive +3 (high AB-titre). The semiquantitative determinations of H. pylori-AB correlated with pepsinogen A, C and gastrin. Patients with H. pylori-AB positive +3 showed significantly higher values of pepsinogen C (p < or = 0.01) as well as pepsinogen A and gastrin (p < or = 0.05) than H. pylori-AB negative patients. Significantly increased levels of pepsinogen A (> 150 ng/ml) and C (> 25 ng/ml) were found to occur in 39% and 100% of patients with high H. pylori-AB titres. The measurement of serum pepsinogen C concentrations may provide additional diagnostic information of the extent of mucosal lesions in patients with positive H. pylori-AB titres treated with antirheumatic drugs. Our findings suggest that the semi-quantitative classification of positive AB-results can be useful in cases determining H. pylori infection and mucosal irritation if other investigations are not available.

  1. [Influence of high concentration of antibodies to NGF during early embryogenesis on formation of mice behavior in postnatal period].

    PubMed

    Rodionov, A N; Lobanov, A V; Morozov, S G; Sidiakin, A A; Anikina, O M; Gribova, I E; Rybakov, A S; Protsenko, A N; Murashev, A N; Kliushnik, T P

    2012-01-01

    In this work the influence of high concentration of antibodies to NGF on mouse's progeny has been investigated. During immunization with NGF the highest concentrations of antibodies were created in the first and third days of pregnancy (in different groups of animals). The dependence of abnormalities of mice postnatal development on level of antibodies to NGF at different stages of early embryogenesis has been established. Increasing of abnormalities in the formation of early behavioral acts and more clinically apparent anomalies in the somatic maturation in case of maximum of antibodies on day I of pregnancy has been showed. Immune responses to NGF during early embryogenesis of mice cause lag in the formation of behavioral acts. The latter are characterized by difficulties in sensor-motor coordination of the limbs and more clinically apparent in mice with a maximum of antibodies on day 1 of embryonic development. Infantilism in developing of contacts between progeny and mothers detected in mice with immune reactions may be a sign of serious mental dysontogenesis. The accelerated development of working memory established in mice with immune response to NGF requires further study of the development of cognitive abilities in these animals. The obtained results illustrate the important regulatory role of NGF at the early stages of development of the nervous system.

  2. Serum pepsinogen I and II concentrations and IgG antibody to Helicobacter pylori in dyspeptic patients.

    PubMed Central

    Biasco, G; Paganelli, G M; Vaira, D; Holton, J; Di Febo, G; Brillanti, S; Miglioli, M; Barbara, L; Samloff, I M

    1993-01-01

    AIMS--To investigate the association between histologically confirmed gastritis, carriage of Helicobacter pylori and pepsinogen (PG) I and PG II concentrations. METHODS--Prospective study of 81 dyspeptic patients undergoing upper gastrointestinal endoscopy was made. The extent of gastric mucosal inflammation and the presence of H pylori was determined, and serology to evaluate PG I and II concentrations and IgG titres to H pylori was carried out. RESULTS--The presence of H pylori was strongly correlated with high IgG antibody titres to H pylori and gastritis. Patients who were H pylori positive had significantly higher PG I and PG II concentrations and a significantly lower PG I:PG II ratio than patients who were negative for H pylori. In 13 patients with duodenal ulcer and H pylori positive gastritis serum PG I concentrations were significantly higher than in H pylori positive patients without duodenal ulcer. Significant correlations were found between the age of patients and serum PG II, the PG I:PG II ratio, IgG antibodies to H pylori, the severity of body gastritis and H pylori infection, and between the degree of gastritis in the body of the stomach and the PG II concentration. CONCLUSIONS--Serum PG I and II concentrations, together with a fall in the PG I:PG II ratio, could be used as predictors of H pylori infection as well as serum IgG antibody response to H pylori. PMID:8227432

  3. Age related variations of serum concentrations of normally occurring IgG antibodies to Clostridium perfringens.

    PubMed Central

    Zarén, E; Schwan, A; Frenckner, B

    1987-01-01

    In studies using indirect immunofluorescence IgG antibodies to Clostridium perfringens were found in sera from healthy adults. Sera from 236 healthy children were examined. The normally occurring IgG antibodies to C perfringens were found to have an age related variation. Preliminary data suggest that they are not correlated to C perfringens alpha toxin. The antigen(s) against which the antibodies are directed is/are probably part of the cell wall, but its/their exact nature is not known. PMID:2881950

  4. Weak Interactions Govern the Viscosity of Concentrated Antibody Solutions: High-Throughput Analysis Using the Diffusion Interaction Parameter

    PubMed Central

    Connolly, Brian D.; Petry, Chris; Yadav, Sandeep; Demeule, Barthélemy; Ciaccio, Natalie; Moore, Jamie M.R.; Shire, Steven J.; Gokarn, Yatin R.

    2012-01-01

    Weak protein-protein interactions are thought to modulate the viscoelastic properties of concentrated antibody solutions. Predicting the viscoelastic behavior of concentrated antibodies from their dilute solution behavior is of significant interest and remains a challenge. Here, we show that the diffusion interaction parameter (kD), a component of the osmotic second virial coefficient (B2) that is amenable to high-throughput measurement in dilute solutions, correlates well with the viscosity of concentrated monoclonal antibody (mAb) solutions. We measured the kD of 29 different mAbs (IgG1 and IgG4) in four different solvent conditions (low and high ion normality) and found a linear dependence between kD and the exponential coefficient that describes the viscosity concentration profiles (|R| ≥ 0.9). Through experimentally measured effective charge measurements, under low ion normality where the electroviscous effect can dominate, we show that the mAb solution viscosity is poorly correlated with the mAb net charge (|R| ≤ 0.6). With this large data set, our results provide compelling evidence in support of weak intermolecular interactions, in contrast to the notion that the electroviscous effect is important in governing the viscoelastic behavior of concentrated mAb solutions. Our approach is particularly applicable as a screening tool for selecting mAbs with desirable viscosity properties early during lead candidate selection. PMID:22828333

  5. Use of anti-Aedes aegypti salivary extract antibody concentration to correlate risk of vector exposure and dengue transmission risk in Colombia.

    PubMed

    Londono-Renteria, Berlin; Cardenas, Jenny C; Cardenas, Lucio D; Christofferson, Rebecca C; Chisenhall, Daniel M; Wesson, Dawn M; McCracken, Michael K; Carvajal, Daisy; Mores, Christopher N

    2013-01-01

    Norte de Santander is a region in Colombia with a high incidence of dengue virus (DENV). In this study, we examined the serum concentration of anti-Aedes salivary gland extract (SGE) antibodies as a biomarker of DENV infection and transmission, and assessed the duration of anti-SGE antibody concentration after exposure to the vector ceased. We also determined whether SGE antibody concentration could differentiate between positive and negative DENV infected individuals and whether there are differences in exposure for each DENV serotype. We observed a significant decrease in the concentration of IgG antibodies at least 40 days after returning to an "Ae. aegypti-free" area. In addition, we found significantly higher anti-SGE IgG concentrations in DENV positive patients with some difference in exposure to mosquito bites among DENV serotypes. We conclude that the concentration of IgG antibodies against SGE is an accurate indicator of risk of dengue virus transmission and disease presence.

  6. Baculovirus-based nasal drop vaccine confers complete protection against malaria by natural boosting of vaccine-induced antibodies in mice.

    PubMed

    Yoshida, Shigeto; Araki, Hitomi; Yokomine, Takashi

    2010-02-01

    Blood-stage malaria parasites ablate memory B cells generated by vaccination in mice, resulting in diminishing natural boosting of vaccine-induced antibody responses to infection. Here we show the development of a new vaccine comprising a baculovirus-based Plasmodium yoelii 19-kDa carboxyl terminus of merozoite surface protein 1 (PyMSP1(19)) capable of circumventing the tactics of parasites in a murine model. The baculovirus-based vaccine displayed PyMSP1(19) on the surface of the virus envelope in its native three-dimensional structure. Needle-free intranasal immunization of mice with the baculovirus-based vaccine induced strong systemic humoral immune responses with high titers of PyMSP1(19)-specific antibodies. Most importantly, this vaccine conferred complete protection by natural boosting of vaccine-induced PyMSP1(19)-specific antibody responses shortly after challenge. The protective mechanism is a mixed Th1/Th2-type immunity, which is associated with the Toll-like receptor 9 (TLR9)-dependent pathway. The present study offers a novel strategy for the development of malaria blood-stage vaccines capable of naturally boosting vaccine-induced antibody responses to infection.

  7. Protooncogene bcl-2 gene transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation.

    PubMed Central

    Weller, M; Malipiero, U; Aguzzi, A; Reed, J C; Fontana, A

    1995-01-01

    The majority of human malignant glioma cells express Fas/APO-1 and are susceptible to Fas/APO-1 antibody-mediated apoptosis in vitro. The sensitivity of Fas/APO-1-positive glioma cell lines to Fas/APO-1 antibody-mediated killing correlates inversely with the constitutive expression of the antiapoptotic protooncogene bcl-2. Here we report that BCL-2 protein expression of human glial tumors in vivo correlates with malignant transformation in that BCL-2 immunoreactive glioma cells were more abundant in WHO grade III/IV gliomas than in grade I/II gliomas. Fas/APO-1 antibody-sensitive human glioma cell lines stably transfected with a murine bcl-2 cDNA acquired resistance to Fas/APO-1 antibody-mediated apoptosis. Forced expression of bcl-2 also attenuated TNF alpha-mediated cytotoxicity of glioma cell lines in the presence of actinomycin D and cycloheximide and conferred partial protection from irradiation and the cancer chemotherapy drugs, cisplatin and BCNU. Preexposure of the glioma cell lines to the cytokines, IFN gamma and TNF alpha, which sensitize for Fas/APO-1-dependent killing, partially overcame bcl-2-mediated rescue from apoptosis, suggesting that multimodality immunotherapy involving cytokines and Fas/APO-1 targeting might eventually provide a promising approach to the treatment of human malignant gliomas. Images PMID:7539458

  8. Concentrations of Pneumococcal IgA and IgM are compromised in some individuals with antibody deficiencies.

    PubMed

    Echeverría de Carlos, Ainara; Gómez de la Torre, Ricardo; García Carus, Enrique; Caminal Montero, Luis; Bernardino Díaz López, Jose; Suárez Casado, Hector; Molinos Matin, Luis; Tricas Aizpún, Lourdes; Harding, Stephen; Parker, Antony R

    2017-06-15

    The response to pneumococcal vaccination is assessed by measurement of antigen specific IgG only and is compromised in a number of antibody deficiencies. We measured the concentrations of Pneumococcal IgA and IgM in individuals with both normal and abnormal pneumococcal capsular polysaccharide (PCP) IgG concentrations. A higher number of individuals had abnormal pre-vaccination IgA and IgM concentrations below the lower limit of the normal range compared to the control group. Post vaccination a lower number of individuals had IgA and IgM concentrations below the upper limit of the normal range compared to the control group. Non responders had a higher percentage of individuals with a prior history of infection. In addition, individuals with a history of prior infection had lower pre- and post-vaccination concentrations of PCP IgG, IgA, and IgM. Post-vaccination IgA and IgM concentrations identified four groups of responses which correlated with prior history of infection. A higher percentage of individuals with abnormal PCP IgA and IgM concentrations had a history of prior infection compared to the percentage of individuals with normal concentrations. In individuals with an antibody deficiency, measurement of Pneumococcal IgA and IgM correlates with the number of individuals with prior history of infection.

  9. Deconvolution of antibody affinities and concentrations by non-linear regression analysis of competitive ELISA data.

    SciTech Connect

    Stevens, F. J.; Bobrovnik, S. A.; Biosciences Division; Palladin Inst. Biochemistry

    2007-12-01

    Physiological responses of the adaptive immune system are polyclonal in nature whether induced by a naturally occurring infection, by vaccination to prevent infection or, in the case of animals, by challenge with antigen to generate reagents of research or commercial significance. The composition of the polyclonal responses is distinct to each individual or animal and changes over time. Differences exist in the affinities of the constituents and their relative proportion of the responsive population. In addition, some of the antibodies bind to different sites on the antigen, whereas other pairs of antibodies are sterically restricted from concurrent interaction with the antigen. Even if generation of a monoclonal antibody is the ultimate goal of a project, the quality of the resulting reagent is ultimately related to the characteristics of the initial immune response. It is probably impossible to quantitatively parse the composition of a polyclonal response to antigen. However, molecular regression allows further parameterization of a polyclonal antiserum in the context of certain simplifying assumptions. The antiserum is described as consisting of two competing populations of high- and low-affinity and unknown relative proportions. This simple model allows the quantitative determination of representative affinities and proportions. These parameters may be of use in evaluating responses to vaccines, to evaluating continuity of antibody production whether in vaccine recipients or animals used for the production of antisera, or in optimizing selection of donors for the production of monoclonal antibodies.

  10. Specific ion-protein interactions dictate solubility behavior of a monoclonal antibody at low salt concentrations.

    PubMed

    Zhang, Le; Zhang, Jifeng

    2012-09-04

    The perturbation of salt ions on the solubility of a monoclonal antibody was systematically studied at various pHs in Na(2)SO(4), NaNO(3), NaCl, NaF, MgSO(4), Mg(NO(3))(2) and MgCl(2) solutions below 350 mM. At pH 7.1, close to the pI, all of the salts increased the solubility of the antibody, following the order of SO(4)(2-) > NO(3)(-) > Cl(-) > F(-) for anions and Mg(2+) > Na(+) for cations. At pH 5.3 where the antibody had a net positive charge, the anions initially followed the order of SO(4)(2-) > NO(3)(-) > Cl(-) > F(-) for effectiveness in reducing the solubility and then switched to increasing the solubility retaining the same order. Furthermore, the antibody was more soluble in the Mg(2+) salt solutions than in the corresponding Na(+) salt solutions with the same anion. At pH 9.0 where the antibody had a net negative charge, an initial decrease in the protein solubility was observed in the solutions of the Mg(2+) salts and NaF, but not in the rest of the Na(+) salt solutions. Then, the solubility of the antibody was increased by the anions in the order of SO(4)(2-) > NO(3)(-) > Cl(-) > F(-). The above complex behavior is explained based on the ability of both cation and anion from a salt to modulate protein-protein interactions through their specific binding to the protein surface.

  11. Assessment of the Protein-Protein Interactions in a Highly Concentrated Antibody Solution by Using Raman Spectroscopy.

    PubMed

    Ota, Chikashi; Noguchi, Shintaro; Nagatoishi, Satoru; Tsumoto, Kouhei

    2016-04-01

    To investigate the protein-protein interactions of a highly concentrated antibody solution that could cause oligomerization or aggregation and to develop a better understanding of the optimization of drug formulations. In this study, we used Raman spectroscopy to investigate the structure and interactions of a highly concentrated antibody solution over a wide range of concentrations (10-200 mg/mL) with the aid of a multivariate analysis. Our analysis of the amide I band, I 856 /I 830 of Tyr, and the relative intensity at 1004 cm(-1) of the Phe and OH stretching region at around 3000 cm(-1) showed that across this wide range of concentrations, the secondary structure of the IgG molecules did not change; however, short-range attractive interactions around the Tyr and Phe residues occurred as the distance between the IgG molecules decreased with increasing concentration. Analysis of the OH stretching region at around 3000 cm(-1) showed that these short-range attractive interactions correlated with the amount of hydrated water around the IgG molecules. Our data show that Raman spectroscopy can provide valuable information of the protein-protein interactions based on conformational approaches to support conventional colloidal approaches, especially for analyses of highly concentrated solutions.

  12. Utility of measuring serum concentrations of anti-TNF agents and anti-drug antibodies in inflammatory bowel disease.

    PubMed

    Guerra, Iván; Chaparro, María; Bermejo, Fernando; Gisbert, Javier P

    2011-07-01

    Tumor necrosis factor alpha (TNFα) is a cytokine with a critical role in the pathogenesis of some chronic inflammatory diseases, such as inflammatory bowel diseases. Anti-TNF agents, which neutralize the biological activity of TNFα, are widely used among the different therapeutic options for the treatment of patients with inflammatory bowel diseases. These drugs are very useful in clinical practice, but some patients experience lack and loss of response during the treatment. Drug serum concentration, antibodies against anti-TNF agents, clearance of the drug, formation of immune complexes, a more severe disease and probably other unknown factors can influence the treatment's efficacy. Nowadays, the management of patients with lack or loss of response is empirical. The measurement of drug concentrations and antibodies against anti-TNF agents might be useful for improving the selection of patients that will benefit from the maintenance treatment. In clinical practice, these methods may help us decide which strategy will be used in cases of loss of response: treatment intensification, shortening the infusion interval, increasing the dose, switching to another anti-TNF agent or to a drug with another mechanism of action. The optimal strategy in the future may be comprised of an early detection of loss of response to the treatment by assessing clinical symptoms and finding evidence of activity of the disease on endoscopic or radiological examinations when necessary, as well as a better management of anti-TNF treatment aided by measuring the serum concentration of the drug and antibodies against the drug.

  13. High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

    PubMed Central

    Rota, Jennifer S.; Hickman, Carole J.; Mercader, Sara; Redd, Susan; McNall, Rebecca J.; Williams, Nobia; McGrew, Marcia; Walls, M. Laura; Rota, Paul A.; Bellini, William J.

    2016-01-01

    In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. PMID:27335386

  14. Structure-activity relationship for hydrophobic salts as viscosity-lowering excipients for concentrated solutions of monoclonal antibodies.

    PubMed

    Guo, Zheng; Chen, Alvin; Nassar, Roger A; Helk, Bernhard; Mueller, Claudia; Tang, Yu; Gupta, Kapil; Klibanov, Alexander M

    2012-11-01

    To discover, elucidate the structure-activity relationship (SAR), and explore the mechanism of action of excipients able to drastically lower the viscosities of concentrated aqueous solutions of humanized monoclonal antibodies (MAbs). Salts prepared from hydrophobic cations and anions were dissolved into humanized MAbs solutions. Viscosities of the resulting solutions were measured as a function of the nature and concentration of the salts and MAbs. Even at moderate concentrations, some of the salts prepared herein were found to reduce over 10-fold the viscosities of concentrated aqueous solutions of several MAbs at room temperature. To be potent viscosity-lowering excipients, the ionic constituents of the salts must be hydrophobic, bulky, and aliphatic. A mechanistic hypothesis explaining the observed salt effects on MAb solutions' viscosities was proposed and verified.

  15. Antibodies to parvovirus, distemper virus and adenovirus conferred to household dogs using commercial combination vaccines containing Leptospira bacterin.

    PubMed

    Taguchi, M; Namikawa, K; Maruo, T; Lynch, J; Sahara, H

    2010-12-11

    To examine how the inclusion (+) or exclusion (-) of inactivated Leptospira antigens in a vaccine for canine parvovirus type 2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type 2 (CAdV-2) affects antibody titres to CPV-2, CDV and CAdV-1 antigens, household dogs were vaccinated with commercially available vaccines from one of three manufacturers. CPV-2, CDV and CAdV-1 antibody titres were measured 11 to 13 months later and compared within three different age groups and three different bodyweight groups. There were significant differences between CPV-2 antibody titres in dogs vaccinated with (+) vaccine and those vaccinated with (-) vaccine for two products in the two-year-old group and for one product in the greater than seven-year-old group; no significant differences were seen that could be attributed to bodyweight. No differences in CDV antibody titres were observed within age groups, but a significant difference was seen in the 11 to 20 kg weight group for one product. Significant differences in CAdV-1 antibody titres were seen for one product in both the two-year-old group and the ≤10 kg weight group.

  16. Domain based assays of individual antibody concentrations in an oligoclonal combination targeting a single protein

    PubMed Central

    Meng, Q.; Li, M.; Silberg, M.A.; Conrad, F.; Bettencourt, J.; To, R.; Huang, C.; Ma, J.; Meyer, K.; Shimizu, R.; Cao, L.; Tomic, M.T.; Marks, J.D.

    2014-01-01

    Quantitation of individual mAbs within a combined antibody drug product is required for preclinical and clinical drug development including pharmacokinetics (PK), toxicology, stability and biochemical characterization studies of such drugs. We have developed an antitoxin (XOMA 3AB) consisting of three recombinant monoclonal antibodies (mAbs) that potently neutralizes the known subtypes of type A botulinum neurotoxin (BoNT/A). The three mAbs bind non-overlapping BoNT/A epitopes with high affinity. XOMA3AB is being developed as a treatment for botulism resulting from BoNT/A. To develop antibody-specific assays, we cloned, expressed, and purified BoNT/A domains from E. coli. Each mAb bound only to its specific domain with affinity comparable to the binding to holotoxin. MAb specific domains were used to develop an ELISA for characterization of the integrity and binding activity of the three mAbs in the drug product. An electrochemiluminescence bridging assay was also developed that is robust to interference from components in serum and we demonstrate that it can be used for PK assays. This type of antigen engineering to generate mAb-specific domains is a general method allowing quantitation and characterization of individual mAbs in a mAb cocktail that bind the same protein and is superior to anti-idiotype approaches. PMID:22037290

  17. Pharmacological concentrations of rFVIIa restore hemostasis independent of tissue factor in antibody-induced hemophilia mice

    PubMed Central

    KESHAVA, S.; SUNDARAM, J.; RAJULAPATI, A.; PENDURTHI, U.R.; RAO, L.V.M.

    2016-01-01

    Summary Background Recombinant factor VIIa (rFVIIa) has been used widely for treating hemophilia patients with inhibitory autoantibodies against factor VIII or IX. Its mechanism of action is not entirely known. A majority of in vitro studies suggested that pharmacological concentrations of rFVIIa restore hemostasis in hemophilia in a phospholipid-dependent mechanism, independent of tissue factor (TF). However, a few studies suggested that a TF-dependent mechanism plays a primary role in rFVIIa correction of bleeding in hemophilia patients. Here, we investigated the potential contribution of TF in rFVIIa-induced hemostasis in hemophilia employing a model system of FVIII antibody-induced hemophilia in TF transgenic mice. Methods Mice expressing low levels of human TF (LTF mice), relatively high levels of human TF (HTF mice) or wild-type mice (WT mice) were administered with neutralizing anti-FVIII antibodies to induce hemophilia in these mice. The mice were then treated with varying concentrations of rFVIIa. rFVIIa-induced hemostasis was evaluated with the saphenous vein bleeding model. Results Administration of FVIII inhibitory antibodies induced the hemophilic bleeding phenotype in all three genotypes. rFVIIa administration rescued the bleeding phenotype in all three genotypes. No significant differences were observed in rFVIIa-induced correction in the bleeding of LTF and HTF mice administered with FVIII antibodies. Conclusions Our results provide strong evidence supporting that the hemostatic effect of pharmacological doses of rFVIIa stems from a TF-independent mechanism. PMID:26727350

  18. Pharmacological concentrations of recombinant factor VIIa restore hemostasis independent of tissue factor in antibody-induced hemophilia mice.

    PubMed

    Keshava, S; Sundaram, J; Rajulapati, A; Pendurthi, U R; Rao, L V M

    2016-03-01

    ESSENTIALS: The role of tissue factor (TF) in recombinant factor VIIa (rFVIIa) therapy in hemophilia is unclear. An acquired mouse hemophilia model with very low or normal levels of human TF was used in the study. rFVIIa is equally effective in correcting the bleeding in mice expressing low or normal levels of TF. Pharmacological doses of rFVIIa restore hemostasis in hemophilia independent of TF. Recombinant factor VIIa (rFVIIa) has been used widely for treating hemophilia patients with inhibitory autoantibodies against factor VIII or IX. Its mechanism of action is not entirely known. A majority of in vitro studies suggested that pharmacological concentrations of rFVIIa restore hemostasis in hemophilia in a phospholipid-dependent manner, independent of tissue factor (TF). However, a few studies suggested that a TF-dependent mechanism has a primary role in correction of bleeding by rFVIIa in hemophilia patients. Here, we investigated the potential contribution of TF in rFVIIa-induced hemostasis in hemophilia employing a model system of FVIII antibody-induced hemophilia in TF transgenic mice. Mice expressing low levels of human TF (LTF mice), mice expressing relatively high levels of human TF (HTF mice) and wild-type mice (WT mice) had neutralizing anti-FVIII antibodies administered in order to induce hemophilia in these mice. The mice were then treated with varying concentrations of rFVIIa. rFVIIa-induced hemostasis was evaluated with the saphenous vein bleeding model. Administration of FVIII inhibitory antibodies induced the hemophilic bleeding phenotype in all three genotypes. rFVIIa administration rescued the bleeding phenotype in all three genotypes. No significant differences were observed in rFVIIa-induced correction of bleeding between LTF and HTF mice that had FVIII antibodies administered. Our results provide strong evidence supporting the suggestion that the hemostatic effect of pharmacological doses of rFVIIa stems from a TF-independent mechanism. © 2016

  19. Applying photoacoustics to quantification of melanin concentration in retinal pigment epithelium (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Shu, Xiao; Zhang, Hao F.; Liu, Wenzhong

    2016-03-01

    The melanin in the retinal pigment epithelium (RPE) protects retina and other ocular tissues by photo-screening and acting as antioxidant and free radical scavenger. It helps maintain normal visual functions since human eye is subjected to lifelong high oxygen stress and photon exposure. Loss of the RPE melanin weakens the protection mechanism and jeopardizes ocular health. Local decrease in the RPE melanin concentration is believed to be both a cause and a sign of early-stage age-related macular degeneration (AMD), the leading blinding disease in developed world. Current technology cannot quantitatively measure the RPE melanin concentration which might be a promising marker in early AMD screening. Photoacoustic ophthalmoscopy (PAOM), as an emerging optical absorption-based imaging technology, can potentially be applied to measure the RPE melanin concentration if the dependence of the detectable photoacoustic (PA) signal amplitudes on the RPE melanin concentrations is verified. In this study, we tested the feasibility of using PA signal ratio from RPE melanin and the nearby retinal blood vessels as an indicator of the RPE melanin variation. A novel whole eye optical model was designed and Monte Carlo modeling of light (MCML) was employed. We examined the influences on quantification from PAOM axial resolution, the depth and diameter of the retinal blood vessel, and the RPE thickness. The results show that the scheme is robust to individual histological and illumination variations. This study suggests that PAOM is capable of quantitatively measuring the RPE melanin concentration in vivo.

  20. Transgenic expression in citrus of single-chain antibody fragments specific to Citrus tristeza virus confers virus resistance.

    PubMed

    Cervera, Magdalena; Esteban, Olga; Gil, Maite; Gorris, M Teresa; Martínez, M Carmen; Peña, Leandro; Cambra, Mariano

    2010-12-01

    Citrus tristeza virus (CTV) causes one of the most destructive viral diseases of citrus worldwide. Generation of resistant citrus genotypes through genetic engineering could be a good alternative to control CTV. To study whether production of single-chain variable fragment (scFv) antibodies in citrus could interfere and immunomodulate CTV infection, transgenic Mexican lime plants expressing two different scFv constructs, separately and simultaneously, were generated. These constructs derived from the well-referenced monoclonal antibodies 3DF1 and 3CA5, specific against CTV p25 major coat protein, whose mixture is able to detect all CTV isolates characterized so far. ScFv accumulation levels were low and could be readily detected just in four transgenic lines. Twelve homogeneous and vigorous lines were propagated and CTV-challenged by graft inoculation with an aggressive CTV strain. A clear protective effect was observed in most transgenic lines, which showed resistance in up to 40-60% of propagations. Besides, both a delay in symptom appearance and attenuation of symptom intensity were observed in infected transgenic plants compared with control plants. This effect was more evident in lines carrying the 3DF1scFv transgene, being probably related to the biological functions of the epitope recognized by this antibody. This is the first report describing successful protection against a pathogen in woody transgenic plants by ectopic expression of scFv recombinant antibodies.

  1. Antibody Engineering and Therapeutics

    PubMed Central

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  2. Telecommunications Policy Research Conference. Media Concentration and the First Amendment Section. Papers.

    ERIC Educational Resources Information Center

    Telecommunications Policy Research Conference, Inc., Washington, DC.

    These two papers consider the implications of industry concentration in the mass media industry. The first, "Selling the Store: Policy Implications of the 1986 Bonanza in Television Station Transfers" (Joseph Foley, Ohio State University), analyzes the relationship between key market variables and prices paid in 1986 television stations…

  3. Cow-level association between serum 25-hydroxyvitamin D concentration and Mycobacterium avium subspecies paratuberculosis antibody seropositivity: a pilot study.

    PubMed

    Sorge, U S; Molitor, T; Linn, J; Gallaher, D; Wells, S W

    2013-02-01

    Vitamin D deficiency has been associated with various human diseases. Therefore, the objective of this study was to evaluate the cow-level association between serum 25-hydroxyvitamin D [25(OH)D] concentration and Mycobacterium avium ssp. paratuberculosis (MAP) seropositivity of dairy cows, adjusting for diet, breed, hair coat color, stage of lactation, reproductive status, and cow age. The sera of 80 MAP antibody ELISA-positive and 80 test-negative herd mates from 5 Minnesota dairy herds were analyzed for 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. The cows' age, production records, and hair coat color were recorded. Additionally, feed samples were obtained and analyzed for vitamin D(2) and vitamin D(3) content. A linear mixed model was used to identify potential predictors for serum 25(OH)D concentration, accounting for herd of origin. The majority of rations analyzed had over 22,000 IU of vitamin D/day (maximum: 52,000 I U/d) and the study cows' average serum 25(OH)D concentration was 62.5 ± 13.8 ng/mL. Serum ELISA-positive cows had, on average, 5.3 ng/mL lower 25(OH)D serum levels than test-negative herd mates. The reproductive status of cows was also associated with the 25(OH)D levels, with fresh cows having the lowest serum concentration. In this cross-sectional study, a temporal or causal association between MAP antibody ELISA status and serum 25(OH)D concentration could not be evaluated. In addition, the high levels of vitamin D in the rations of participating farms and the average 25(OH)D serum concentration suggest that additional supplementation with vitamin D in the ration is likely to be ineffective. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  4. Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial

    PubMed Central

    Sokolove, Jeremy; Schiff, Michael; Fleischmann, Roy; Weinblatt, Michael E; Connolly, Sean E; Johnsen, Alyssa; Zhu, Jin; Maldonado, Michael A; Patel, Salil; Robinson, William H

    2016-01-01

    Objectives To examine whether baseline anti-cyclic citrullinated peptide-2 (CCP2) antibody status and concentration correlated with clinical outcomes in patients treated with abatacept or adalimumab on background methotrexate (MTX) in the 2-year AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE rheumatoid arthritis subjects with background MTX) study. Methods In this exploratory analysis, anti-CCP2 antibody concentration was measured at baseline, and antibody-positive patients were divided into equal quartiles, Q1–Q4, representing increasing antibody concentrations. Clinical outcomes analysed by baseline anti-CCP2 status and quartile included change from baseline in disease activity and disability and remission rates. Results Baseline characteristics were generally comparable across quartiles and treatment groups. In both treatment groups, anti-CCP2 antibody-negative patients responded less well than antibody-positive patients. At year 2, improvements in disease activity and disability and remission rates were similar across Q1–Q3, but were numerically higher in Q4 in the abatacept group; in contrast, treatment effects were similar across all quartiles in the adalimumab group. Conclusions In AMPLE, baseline anti-CCP2 positivity was associated with a better response for abatacept and adalimumab. Patients with the highest baseline anti-CCP2 antibody concentrations had better clinical response with abatacept than patients with lower concentrations, an association that was not observed with adalimumab. Trial registration number NCT00929864. PMID:26359449

  5. Local distribution and concentration of intravenously injected sup 131 I-9. 2. 27 monoclonal antibody in human malignant melanoma

    SciTech Connect

    Del Vecchio, S.; Reynolds, J.C.; Carrasquillo, J.A.; Blasberg, R.G.; Neumann, R.D.; Lotze, M.T.; Bryant, G.J.; Farkas, R.J.; Larson, S.M. )

    1989-05-15

    Regional measurements of {sup 131}I-9.2.27 distribution in human melanoma tumors were obtained using quantitative autoradiography. Tumors were removed from patients 72-96 h after they had received an i.v. injection of 9.15 mCi (100 mg) of {sup 131}I-9.2.27. The autoradiographic images showed that the radioactivity reaching the tumor was heterogeneously distributed. Areas of relative high and low uptake were selected in each tumor. Regions of high activity contained from 51 to 1371 nCi/g, while areas with low uptake had radioactivity ranging from 12 to 487 nCi/g. The reliability of the autoradiographic measurements was demonstrated by the strong positive correlation with direct tissue sample counting (r = 0.994 P less than 0.001). Since comparative immunocytochemistry showed a homogeneous and diffuse staining of target antigen on viable tumor cells, variability of monoclonal antibody uptake within individual tumors was not primarily due to heterogeneity of antigen expression in these cases. However, antigen levels accounted for some of the variation from tumor to tumor. When immunoperoxidase staining was repeated on adjacent sections without the addition of 9.2.27, it confirmed the nonuniform distribution of monoclonal antibody found at autoradiography. Thus, quantitative autoradiography gives information about the distribution and the local concentration of radioactive antibody in tumors allowing calculation of the radiation dose delivered to small regions within tumors.

  6. In Vitro Neutralization of Low Dose Inocula at Physiological Concentrations of a Monoclonal Antibody Which Protects Macaques against SHIV Challenge

    PubMed Central

    Davis, David; Koornstra, Wim; Fagrouch, Zahra; Verschoor, Ernst J.; Heeney, Jonathan L.; Bogers, Willy M. J. M.

    2013-01-01

    Background Passive transfer of antibodies can be protective in the simian human immunodeficiency virus (SHIV) – rhesus macaque challenge model. The human monoclonal antibody IgG1 b12 neutralizes human immunodeficiency type 1 (HIV-1) in vitro and protects against challenge by SHIV. Our hypothesis is that neutralizing antibodies can only completely inactivate a relatively small number of infectious virus. Methods And Findings We have used GHOST cell assays to quantify individual infectious events with HIV-1SF162 and its SHIV derivatives: the relatively neutralization sensitive SHIVSF162P4 isolate and the more resistant SHIVSF162P3. A plot of the number of fluorescent GHOST cells with increasing HIV-1SF162 dose is not linear. It is likely that with high-dose inocula, infection with multiple virus produces additive fluorescence in individual cells. In studies of the neutralization kinetics of IgG1 b12 against these isolates, events during the absorption phase of the assay, as well as the incubation phase, determine the level of neutralization. It is possible that complete inactivation of a virus is limited to the time it is exposed on the cell surface. Assays can be modified so that neutralization of these very low doses of virus can be quantified. A higher concentration of antibody is required to neutralize the same dose of resistant SHIVSF162P3 than the sensitive SHIVSF162P4. In the absence of selection during passage, the density of the CCR5 co-receptor on the GHOST cell surface is reduced. Changes in the CD4 : CCR5 density ratio influence neutralization. Conclusions Low concentrations of IgG1 b12 completely inactivate small doses of the neutralization resistant SHIV SF162P3. Assays need to be modified to quantify this effect. Results from modified assays may predict protection following repeated low-dose shiv challenges in rhesus macaques. It should be possible to induce this level of antibody by vaccination so that modified assays could predict the outcome of

  7. In vitro neutralization of low dose inocula at physiological concentrations of a monoclonal antibody which protects macaques against SHIV challenge.

    PubMed

    Davis, David; Koornstra, Wim; Fagrouch, Zahra; Verschoor, Ernst J; Heeney, Jonathan L; Bogers, Willy M J M

    2013-01-01

    Passive transfer of antibodies can be protective in the simian human immunodeficiency virus (SHIV)--rhesus macaque challenge model. The human monoclonal antibody IgG1 b12 neutralizes human immunodeficiency type 1 (HIV-1) in vitro and protects against challenge by SHIV. Our hypothesis is that neutralizing antibodies can only completely inactivate a relatively small number of infectious virus. We have used GHOST cell assays to quantify individual infectious events with HIV-1SF162 and its SHIV derivatives: the relatively neutralization sensitive SHIV(SF162P4) isolate and the more resistant SHIV(SF162P3). A plot of the number of fluorescent GHOST cells with increasing HIV-1SF162 dose is not linear. It is likely that with high-dose inocula, infection with multiple virus produces additive fluorescence in individual cells. In studies of the neutralization kinetics of IgG1 b12 against these isolates, events during the absorption phase of the assay, as well as the incubation phase, determine the level of neutralization. It is possible that complete inactivation of a virus is limited to the time it is exposed on the cell surface. Assays can be modified so that neutralization of these very low doses of virus can be quantified. A higher concentration of antibody is required to neutralize the same dose of resistant SHIV(SF162P3) than the sensitive SHIV(SF162P4). In the absence of selection during passage, the density of the CCR5 co-receptor on the GHOST cell surface is reduced. Changes in the CD4 : CCR5 density ratio influence neutralization. Low concentrations of IgG1 b12 completely inactivate small doses of the neutralization resistant SHIV(SF162P3). Assays need to be modified to quantify this effect. Results from modified assays may predict protection following repeated low-dose shiv challenges in rhesus macaques. It should be possible to induce this level of antibody by vaccination so that modified assays could predict the outcome of human trials.

  8. Positive antibody response to vaccination in adolescence predicts lower C-reactive protein concentration in young adulthood in the Philippines

    PubMed Central

    McDade, Thomas W.; Adair, Linda; Feranil, Alan B.; Kuzawa, Christopher

    2010-01-01

    Objectives Inflammation has been associated with a wide range of chronic degenerative diseases, but the developmental factors contributing to the regulation of inflammation are poorly understood. This study investigates the within-individual association between antibody response to vaccination in adolescence and C-reactive protein (CRP) concentration in young adulthood. Methods In 1998-99, at age 14-15 years, a subset of participants (N=96) in the Cebu Longitudinal Health and Nutrition Survey were administered a typhoid vaccine, and baseline and follow up blood samples were drawn to assess the strength of the antibody response to vaccination. In 2005, at age 20-21 years, blood samples were drawn from the full cohort for measurement of CRP. N=74 individuals had complete data at both time points. Bivariate associations and multivariate logistic regression models were evaluated to test the hypothesis that vaccine responsiveness in adolescence was significantly associated with CRP level in young adulthood. Results There was a strong and statistically significant association between antibody response to vaccination in adolescence and CRP in young adulthood. Median CRP was more than four times higher among non-responders than responders, and non-responders were 2.3 to 3.6 times more likely to have CRP in the top tertile of the sample distribution. Conclusions This study provides evidence for a prospective, within-individual link between more effective antibody-mediated immune defenses and lower levels of inflammation. In the context of prior research in this population, these results suggest that early environments are important determinants of multiple aspects of an individual’s immuno-phenotype. PMID:21484910

  9. Resistance to neutralization by broadly reactive antibodies to the human immunodeficiency virus type 1 gp120 glycoprotein conferred by a gp41 amino acid change.

    PubMed Central

    Thali, M; Charles, M; Furman, C; Cavacini, L; Posner, M; Robinson, J; Sodroski, J

    1994-01-01

    A neutralization-resistant variant of human immunodeficiency virus type 1 (HIV-1) that emerged during in vitro propagation of the virus in the presence of neutralizing serum from an infected individual has been described. A threonine-for-alanine substitution at position 582 in the gp41 transmembrane envelope glycoprotein of the variant virus was responsible for the neutralization-resistant phenotype (M.S. Reitz, Jr., C. Wilson, C. Naugle, R. C. Gallo, and M. Robert-Guroff, Cell 54:57-63, 1988). The mutant virus also exhibited reduced sensitivity to neutralization by 30% of HIV-1-positive sera that neutralized the parental virus, suggesting that a significant fraction of the neutralizing activity within these sera can be affected by the amino acid change in gp41 (C. Wilson, M. S. Reitz, Jr., K. Aldrich, P. J. Klasse, J. Blomberg, R. C. Gallo, and M. Robert-Guroff, J. Virol. 64:3240-3248, 1990). It is shown here that the change of alanine 582 to threonine specifically confers resistance to neutralizing by antibodies directed against both groups of discontinuous, conserved epitopes related to the CD4 binding site on the gp120 exterior envelope glycoprotein. Only minor differences in binding of these antibodies to wild-type and mutant envelope glycoproteins were observed. Thus, the antigenic structure of gp120 can be subtly affected by an amino acid change in gp41, with important consequences for sensitivity to neutralization. Images PMID:7507184

  10. Relative EBV antibody concentrations and cost of standard IVIG and CMV-IVIG for PTLD prophylaxis in solid organ transplant patients.

    PubMed

    Ramirez-Avila, L; Garner, O B; Cherry, J D

    2014-09-01

    Some centers prefer CMV-IVIG over IVIG for the prophylaxis of EBV-related PTLD in solid organ transplant patients. Our objective was to compare the relative dose-related EBV ELISA antibody concentrations and cost of standard IVIG and CMV-IVIG. The concentration of EBV IgG to VCA was analyzed via ELISA in four lots of IVIG and four lots of CMV-IVIG. Relative EBV ELISA antibody concentrations and cost were compared assuming an IVIG dose of 0.5 gm/kg and CMV-IVIG dose of 0.15 gm/kg in a 50-kg patient. The price of IVIG was $70/gm and CMV-IVIG $430/gm. IVIG contains the same EBV antibody concentrations (20 790 ELISA antibody units/mL) than CMV-IVIG (17 430 ELISA antibody units/mL, p > 0.2) in the four lots of each product sampled. When factoring in the dosing scheme for a 50-kg patient, IVIG contains two times more EBV antibody than CMV-IVIG. Yet, CMV-IVIG is 1.8 times more expensive than IVIG ($3225 vs. $1750). In the four lots of each product sampled, IVIG contains more EBV antibodies and costs less than CMV-IVIG when factoring in the dosing scheme. Studies are needed to determine whether there is clinical efficacy of immunoglobulin products for EBV-related PTLD prophylaxis.

  11. Cosolute effects on the chemical potential and interactions of an IgG1 monoclonal antibody at high concentrations.

    PubMed

    Scherer, Thomas M

    2013-02-28

    The solution thermodynamics and interactions of a reversibly self-associating IgG1 monoclonal antibody have been investigated as a function of cosolute type (NaCl, NaSCN, arginine-HCl) and cosolute concentration over a wide range of protein concentrations (1-235 mg/mL) using static light scattering. The nonideality of mAb solutions is analyzed within the simplifying framework of a two-component system to obtain the dependencies of the excess chemical potential of the mAb on protein and cosolute concentrations. Using hard spheres as a model of mAbs in the absence of intermolecular interactions, the mean interparticle distances can be estimated as a function of antibody concentration. Analysis of MAb1 excess chemical potential and mean intermolecular distance results in a potential function representing the sum of protein-protein interactions and their contributions to solution nonideality. This approach facilitates evaluation of the relative contributions of attractive/repulsive intermolecular interactions and excluded volume effects, as well as the effects of cosolutes on protein multiparticle interactions in crowded conditions. Underlying the dominant effect of volume exclusion at high protein concentrations, attractive interactions were found to be amplified with decreasing intermolecular distances by the MAb1 many-body correlations. Comparison of the cosolute concentration dependence of the protein chemical potential, dμ2(ex)/dC3, across the mAb concentrations demonstrates that MAb1 self-association is reduced with increasing ionic strength and in a series based on cosolute identity; Arg-Cl > NaSCN > NaCl. The effectiveness of arginine-HCl and NaSCN in modulating MAb1 excess chemical potential in concentrated solutions is ascribed to the cosolute's ability to mitigate both electrostatic as well as weaker hydrophobic attractive interactions between MAb1 molecules. This investigation presents the first direct analysis of cosolute specific effects on protein

  12. Antithyroglobulin antibody

    MedlinePlus

    Thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Hypothyroidism - thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Graves disease - thyroglobulin antibody; Underactive thyroid - thyroglobulin antibody

  13. [Effect of tetanus toxoid powder needleless injection on the concentration of serum antibody IgG in mice].

    PubMed

    Wang, Jia-Bo; Zhou, Xu; Wang, Zhe-Wei; Jin, Cheng; Xiao, Xiao-He

    2009-12-01

    In this study, a self-designed powder needleless injection system was compared with subcutaneous injection using a needle and syringe to deliver tetanus toxoid (TT) into mice to elicit immunity. First of all, factors influencing the prepartion of TT into powder by being absorbed on aluminium hydroxide were investigated and the micromeritic characters of Al (OH)3-TT powder were observed with optical microscope and laser particle analyzer. The results showed that salt concentration and absorption time had an enhancive effect on drug loading, but the pH value and temperature did not influence the absorption reaction obviously. The absorption reaction was optimized with sodium chloride concentration of 0.4 mol x L(-1) and lasting for 10 min. The average diameter of Al(OH)3-TT powder prepared with conditions optimized above was (60.6 +/- 4.4) microm. The immunization effect of TT was determined through enzyme-linked immunosorbent assay (ELISA) of the concentration of IgG antibody elicited by TT. With delivery of Al(OH)3-TT (of 30 microg TT) by powder needleless injection to mice, the IgG antibody concentration were (6.19 +/- 0.52) and (10.70 +/- 0.78) U x L(-1) after immunization of 4 and 8 weeks, respectively, while the values were (4.25 +/- 0.58) and (7.48 +/- 0.57) U x L(-1) by subcutaneous injection (of 20 microg TT) using a needle and syringe. The results suggested that the self-designed powder needleless injection of Al(OH)3-TT was comparable to subcutaneous injection with a good immunity.

  14. Aggregation of concentrated monoclonal antibody solutions studied by rheology and neutron scattering

    NASA Astrophysics Data System (ADS)

    Castellanos, Maria Monica; Pathak, Jai; Colby, Ralph

    2013-03-01

    Protein solutions are studied using rheology and scattering techniques to investigate aggregation. Here we present a monoclonal antibody (mAb) that aggregates after incubation at 40 °C (below its unfolding temperature), with a decrease in monomer purity of 6% in 10 days. The mAb solution contains surfactant and behaves as a Newtonian fluid when reconstituted into solution from the lyophilized form (before incubation at 40 °C). In contrast, mAb solutions incubated at 40 °C for 1 month exhibit shear yielding in torsional bulk rheometers. Interfacial rheology reveals that interfacial properties are controlled by the surfactant, producing a negligible surface contribution to the bulk yield stress. These results provide evidence that protein aggregates formed in the bulk are responsible for the yield stress. Small-angle neutron scattering (SANS) measurements show an increase in intensity at low wavevectors (q < 4*10-2 nm-1) that we attribute to protein aggregation, and is not observed in solutions stored at 4 °C for 3 days before the measurement. This work suggests a correlation between the aggregated state of the protein (stability) and the yield stress from rheology. Research funded by MedImmune

  15. Highly specific spectroscopic photoacoustic molecular imaging of dynamic optical absorption shifts of an antibody-ICG contrast agent (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Wilson, Katheryne E.; Bachawal, Sunitha; Abou-Elkacem, Lotfi; Jensen, Kristen C.; Machtaler, Steven; Tian, Lu; Willmann, Juergen K.

    2017-03-01

    Improved techniques for breast cancer screening are critically needed as current methods lack diagnostic accuracy. Using spectroscopic photoacoustic (sPA) molecular imaging with a priori knowledge of optical absorption spectra allows suppression of endogenous background signal, increasing the overall sensitivity and specificity of the modality to exogenous contrast agents. Here, sPA imaging was used to monitor antibody-indocyanine green (ICG) conjugates as they undergo optical absorption spectrum shifts after cellular endocytosis and degradation to allow differentiation between normal murine mammary glands from breast cancer by enhancing molecular imaging signal from target (B7-H3)-bound antibody-ICG. First, B7-H3 was shown to have highly specific (AUC of 0.93) expression on both vascular endothelium and tumor stroma in malignant lesions through quantitative immunohistochemical staining of B7-H3 on 279 human samples (normal (n=53), benign lesions (11 subtypes, n=182), breast cancers (4 subtypes, n=97)), making B7-H3 a promising target for sPA imaging. Second, absorption spectra of intracellular and degraded B7-H3-ICG and Isotype control (Iso-ICG) were characterized through in vitro and in vivo experiments. Finally, a transgenic murine breast cancer model (FVB/N-Tg(MMTVPyMT)634Mul) was imaged, and sPA imaging in found a 3.01 (IQR 2.63, 3.38, P<0.001) fold increase in molecular B7-H3-ICG signal in tumors (n=80) compared to control conditions (B7-H3-ICG in tumor negative animals (n=60), Iso-ICG (n=30), blocking B7-H3+B7-H3-ICG (n=20), and free ICG (n=20)) despite significant tumor accumulation of Iso-ICG, confirmed through ex vivo histology. Overall, leveraging anti-B7-H3 antibody-ICG contrast agents, which have dynamic optical absorption spectra representative of molecular interactions, allows for highly specific sPA imaging of murine breast cancer.

  16. Use of Anti-Aedes aegypti Salivary Extract Antibody Concentration to Correlate Risk of Vector Exposure and Dengue Transmission Risk in Colombia

    PubMed Central

    Londono-Renteria, Berlin; Cardenas, Jenny C.; Cardenas, Lucio D.; Christofferson, Rebecca C.; Chisenhall, Daniel M.; Wesson, Dawn M.; McCracken, Michael K.; Carvajal, Daisy; Mores, Christopher N.

    2013-01-01

    Norte de Santander is a region in Colombia with a high incidence of dengue virus (DENV). In this study, we examined the serum concentration of anti-Aedes salivary gland extract (SGE) antibodies as a biomarker of DENV infection and transmission, and assessed the duration of anti-SGE antibody concentration after exposure to the vector ceased. We also determined whether SGE antibody concentration could differentiate between positive and negative DENV infected individuals and whether there are differences in exposure for each DENV serotype. We observed a significant decrease in the concentration of IgG antibodies at least 40 days after returning to an “Ae. aegypti-free” area. In addition, we found significantly higher anti-SGE IgG concentrations in DENV positive patients with some difference in exposure to mosquito bites among DENV serotypes. We conclude that the concentration of IgG antibodies against SGE is an accurate indicator of risk of dengue virus transmission and disease presence. PMID:24312537

  17. Gold Nanostar Enhanced Surface Plasmon Resonance Detection of an Antibiotic at Attomolar Concentrations via an Aptamer-Antibody Sandwich Assay.

    PubMed

    Kim, Suhee; Lee, Hye Jin

    2017-06-20

    A new sandwich assay for tetracycline (TC) involving a DNA aptamer and antibody pair is demonstrated in conjunction with gold nanostar (GNS) enhanced surface plasmon resonance (SPR) to achieve detection in the low attomolar range. GNS particles were covalently functionalized with the antibody probe (antiTC) and integrated into a surface sandwich assay in conjunction with a SPR gold chip modified with the TC-specific aptamer. After it was demonstrated that both affinity probes can bind simultaneously to TC, optimization of the assay was performed using either antiTC only or GNS-antiTC conjugates to interact with aptamer/TC complexes present on the chip surface. Target concentrations as low as 10 aM could be detected using GNS-antiTC's, which was >10(3) times greater in performance than when using antiTC only. In addition, good selectivity was achieved with respect to other tetracycline derivative antibiotics, such as oxytetracycline (OTC) and chlortetracycline (CTC), both which are structurally similar to TC. As a demonstration of trace antibiotic analysis in environmental samples, the GNS enhanced sandwich assay was applied to analyze TC added to aliquots of local river water and the results validated by comparing to conventional high-performance liquid chromatography (HPLC) analysis.

  18. Kinetic analysis of IgM monoclonal antibodies for determination of dengue sample concentration using SPR technique.

    PubMed

    Jahanshahi, Peyman; Wei, Qin; Jie, Zhang; Ghomeishi, Mostafa; Sekaran, Shamala Devi; Mahamd Adikan, Faisal Rafiq

    2016-08-17

    Surface plasmon resonance (SPR) sensing is recently emerging as a valuable technique for measuring the binding constants, association and dissociation rate constants, and stoichimetry for a binding interaction kinetics in a number of emerging biological areas. This technique can be applied to the study of immune system diseases in order to contribute to improved understanding and evaluation of binding parameters for a variety of interactions between antigens and antibodies biochemically and clinically. Since the binding constants determination of an anti-protein dengue antibody (Ab) to a protein dengue antigen (Ag) is mostly complicated, the SPR technique aids a determination of binding parameters directly for a variety of particular dengue Ag_Ab interactions in the real-time. The study highlights the doctrine of real-time dengue Ag_Ab interaction kinetics as well as to determine the binding parameters that is performed with SPR technique. In addition, this article presents a precise prediction as a reference curve for determination of dengue sample concentration.

  19. Development of an antibody-based, modular biosensor for 129Xe NMR molecular imaging of cells at nanomolar concentrations

    PubMed Central

    Rose, Honor M.; Witte, Christopher; Rossella, Federica; Klippel, Stefan; Freund, Christian; Schröder, Leif

    2014-01-01

    Magnetic resonance imaging (MRI) is seriously limited when aiming for visualization of targeted contrast agents. Images are reconstructed from the weak diamagnetic properties of the sample and require an abundant molecule like water as the reporter. Micromolar to millimolar concentrations of conventional contrast agents are needed to generate image contrast, thus excluding many molecular markers as potential targets. To address this limitation, we developed and characterized a functional xenon NMR biosensor that can identify a specific cell surface marker by targeted 129Xe MRI. Cells expressing the cell surface protein CD14 can be spatially distinguished from control cells with incorporation of as little as 20 nM of the xenon MRI readout unit, cryptophane-A. Cryptophane-A serves as a chemical host for hyperpolarized nuclei and facilitates the sensitivity enhancement achieved by xenon MRI. Although this paper describes the application of a CD14-specific biosensor, the construct has been designed in a versatile, modular fashion. This allows for quick and easy adaptation of the biosensor to any cell surface target for which there is a specific antibody. In addition, the modular design facilitates the creation of a multifunctional probe that incorporates readout modules for different detection methods, such as fluorescence, to complement the primary MRI readout. This modular antibody-based approach not only offers a practical technique with which to screen targets, but one which can be readily applied as the xenon MRI field moves closer to molecular imaging applications in vivo. PMID:25071165

  20. A Nucleic-Acid Hydrolyzing Single Chain Antibody Confers Resistance to DNA Virus Infection in HeLa Cells and C57BL/6 Mice

    PubMed Central

    Lee, Gunsup; Yu, Jaelim; Cho, Seungchan; Byun, Sung-June; Kim, Dae Hyun; Lee, Taek-Kyun; Kwon, Myung-Hee; Lee, Sukchan

    2014-01-01

    Viral protein neutralizing antibodies have been developed but they are limited only to the targeted virus and are often susceptible to antigenic drift. Here, we present an alternative strategy for creating virus-resistant cells and animals by ectopic expression of a nucleic acid hydrolyzing catalytic 3D8 single chain variable fragment (scFv), which has both DNase and RNase activities. HeLa cells (SCH7072) expressing 3D8 scFv acquired significant resistance to DNA viruses. Virus challenging with Herpes simplex virus (HSV) in 3D8 scFv transgenic cells and fluorescence resonance energy transfer (FRET) assay based on direct DNA cleavage analysis revealed that the induced resistance in HeLa cells was acquired by the nucleic acid hydrolyzing catalytic activity of 3D8 scFv. In addition, pseudorabies virus (PRV) infection in WT C57BL/6 mice was lethal, whereas transgenic mice (STG90) that expressed high levels of 3D8 scFv mRNA in liver, muscle, and brain showed a 56% survival rate 5 days after PRV intramuscular infection. The antiviral effects against DNA viruses conferred by 3D8 scFv expression in HeLa cells as well as an in vivo mouse system can be attributed to the nuclease activity that inhibits viral genome DNA replication in the nucleus and/or viral mRNA translation in the cytoplasm. Our results demonstrate that the nucleic-acid hydrolyzing activity of 3D8 scFv confers viral resistance to DNA viruses in vitro in HeLa cells and in an in vivo mouse system. PMID:24968358

  1. Stability of buffer-free freeze-dried formulations: A feasibility study of a monoclonal antibody at high protein concentrations.

    PubMed

    Garidel, Patrick; Pevestorf, Benjamin; Bahrenburg, Sven

    2015-11-01

    We studied the stability of freeze-dried therapeutic protein formulations over a range of initial concentrations (from 40 to 160 mg/mL) and employed a variety of formulation strategies (including buffer-free freeze dried formulations, or BF-FDF). Highly concentrated, buffer-free liquid formulations of therapeutic monoclonal antibodies (mAbs) have been shown to be a viable alternative to conventionally buffered preparations. We considered whether it is feasible to use the buffer-free strategy in freeze-dried formulations, as an answer to some of the known drawbacks of conventional buffers. We therefore conducted an accelerated stability study (24 weeks at 40 °C) to assess the feasibility of stabilizing freeze-dried formulations without "classical" buffer components. Factors monitored included pH stability, protein integrity, and protein aggregation. Because the protein solutions are inherently self-buffering, and the system's buffer capacity scales with protein concentration, we included highly concentrated buffer-free freeze-dried formulations in the study. The tested formulations ranged from "fully formulated" (containing both conventional buffer and disaccharide stabilizers) to "buffer-free" (including formulations with only disaccharide lyoprotectant stabilizers) to "excipient-free" (with neither added buffers nor stabilizers). We evaluated the impacts of varying concentrations, buffering schemes, pHs, and lyoprotectant additives. At the end of 24 weeks, no change in pH was observed in any of the buffer-free formulations. Unbuffered formulations were found to have shorter reconstitution times and lower opalescence than buffered formulations. Protein stability was assessed by visual inspection, sub-visible particle analysis, protein monomer content, charge variants analysis, and hydrophobic interaction chromatography. All of these measures found the stability of buffer-free formulations that included a disaccharide stabilizer comparable to buffer

  2. Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1.

    PubMed

    El-Diwany, Ramy; Cohen, Valerie J; Mankowski, Madeleine C; Wasilewski, Lisa N; Brady, Jillian K; Snider, Anna E; Osburn, William O; Murrell, Ben; Ray, Stuart C; Bailey, Justin R

    2017-02-01

    Broadly-neutralizing monoclonal antibodies (bNAbs) may guide vaccine development for highly variable viruses including hepatitis C virus (HCV), since they target conserved viral epitopes that could serve as vaccine antigens. However, HCV resistance to bNAbs could reduce the efficacy of a vaccine. HC33.4 and AR4A are two of the most potent anti-HCV human bNAbs characterized to date, binding to highly conserved epitopes near the amino- and carboxy-terminus of HCV envelope (E2) protein, respectively. Given their distinct epitopes, it was surprising that these bNAbs showed similar neutralization profiles across a panel of natural HCV isolates, suggesting that some viral polymorphisms may confer resistance to both bNAbs. To investigate this resistance, we developed a large, diverse panel of natural HCV envelope variants and a novel computational method to identify bNAb resistance polymorphisms in envelope proteins (E1 and E2). By measuring neutralization of a panel of HCV pseudoparticles by 10 μg/mL of each bNAb, we identified E1E2 variants with resistance to one or both bNAbs, despite 100% conservation of the AR4A binding epitope across the panel. We discovered polymorphisms outside of either binding epitope that modulate resistance to both bNAbs by altering E2 binding to the HCV co-receptor, scavenger receptor B1 (SR-B1). This study is focused on a mode of neutralization escape not addressed by conventional analysis of epitope conservation, highlighting the contribution of extra-epitopic polymorphisms to bNAb resistance and presenting a novel mechanism by which HCV might persist even in the face of an antibody response targeting multiple conserved epitopes.

  3. Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1

    PubMed Central

    El-Diwany, Ramy; Mankowski, Madeleine C.; Wasilewski, Lisa N.; Brady, Jillian K.; Snider, Anna E.; Osburn, William O.; Murrell, Ben; Ray, Stuart C.

    2017-01-01

    Broadly-neutralizing monoclonal antibodies (bNAbs) may guide vaccine development for highly variable viruses including hepatitis C virus (HCV), since they target conserved viral epitopes that could serve as vaccine antigens. However, HCV resistance to bNAbs could reduce the efficacy of a vaccine. HC33.4 and AR4A are two of the most potent anti-HCV human bNAbs characterized to date, binding to highly conserved epitopes near the amino- and carboxy-terminus of HCV envelope (E2) protein, respectively. Given their distinct epitopes, it was surprising that these bNAbs showed similar neutralization profiles across a panel of natural HCV isolates, suggesting that some viral polymorphisms may confer resistance to both bNAbs. To investigate this resistance, we developed a large, diverse panel of natural HCV envelope variants and a novel computational method to identify bNAb resistance polymorphisms in envelope proteins (E1 and E2). By measuring neutralization of a panel of HCV pseudoparticles by 10 μg/mL of each bNAb, we identified E1E2 variants with resistance to one or both bNAbs, despite 100% conservation of the AR4A binding epitope across the panel. We discovered polymorphisms outside of either binding epitope that modulate resistance to both bNAbs by altering E2 binding to the HCV co-receptor, scavenger receptor B1 (SR-B1). This study is focused on a mode of neutralization escape not addressed by conventional analysis of epitope conservation, highlighting the contribution of extra-epitopic polymorphisms to bNAb resistance and presenting a novel mechanism by which HCV might persist even in the face of an antibody response targeting multiple conserved epitopes. PMID:28235087

  4. A cross-sectional study of tetanus and diphtheria antibody concentrations post vaccination among lung transplant patients compared with healthy individuals.

    PubMed

    Rohde, K A; Cunningham, K C; Henriquez, K M; Nielsen, A R; Worzella, S L; Hayney, M S

    2014-12-01

    Lung transplant (LuTx) patients are routinely immunized against tetanus and diphtheria. However, few studies have been done to measure serologic immunity in the transplant population. The primary objective of this study was to compare tetanus and diphtheria antibody concentrations in LuTx vs. healthy subjects. Serum was used from an available sample of 111 total individuals (n = 36 healthy; n = 75 LuTx). Tetanus and diphtheria antibody concentrations were measured using an enzyme-linked immunosorbant assay method. A statistically significant difference in both tetanus and diphtheria antibody concentrations was found between the groups. The median concentration of tetanus antibody was higher for healthy individuals compared with the LuTx group (3.2 IU/mL [1.2-5.2 interquartile range {IQR}] vs. 1.3 IU/mL [0.4-2.6 IQR], respectively; P = 0.0001). No difference in time was found since the last tetanus-diphtheria vaccine or tetanus-diphtheria-pertussis vaccine dose between the groups (healthy 76.5 months [16-114 IQR] vs. LuTx 74.5 months [45-118 IQR]; P = 0.44). Tetanus and diphtheria immunizations are recommended for LuTx patients to reduce the risk of infection. Because the LuTx group has lower antibody concentrations, further studies should investigate the possible need for more frequent tetanus and diphtheria boosters. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry.

    PubMed

    Li, Qingsheng; Zeng, Ming; Duan, Lijie; Voss, James E; Smith, Anthony J; Pambuccian, Stefan; Shang, Liang; Wietgrefe, Stephen; Southern, Peter J; Reilly, Cavan S; Skinner, Pamela J; Zupancic, Mary L; Carlis, John V; Piatak, Michael; Waterman, Diane; Reeves, R Keith; Masek-Hammerman, Katherine; Derdeyn, Cynthia A; Alpert, Michael D; Evans, David T; Kohler, Heinz; Müller, Sybille; Robinson, James; Lifson, Jeffrey D; Burton, Dennis R; Johnson, R Paul; Haase, Ashley T

    2014-09-15

    We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium. This local Ab production and delivery system correlated spatially and temporally with the maturation of local protection against high-dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of Abs at mucosal frontlines could aid in the development of an effective vaccine to protect women against HIV-1. Copyright © 2014 by The American Association of Immunologists, Inc.

  6. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.

    PubMed

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A; Thörn, Karolina; Cairns, Tina M; Wegmann, Frank; Sattentau, Quentin J; Eisenberg, Roselyn J; Cohen, Gary H; Harandi, Ali M

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

  7. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

    PubMed Central

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A.; Thörn, Karolina; Cairns, Tina M.; Wegmann, Frank; Sattentau, Quentin J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Harandi, Ali M.

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes. PMID:28082979

  8. Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial.

    PubMed

    Sokolove, Jeremy; Schiff, Michael; Fleischmann, Roy; Weinblatt, Michael E; Connolly, Sean E; Johnsen, Alyssa; Zhu, Jin; Maldonado, Michael A; Patel, Salil; Robinson, William H

    2016-04-01

    To examine whether baseline anti-cyclic citrullinated peptide-2 (CCP2) antibody status and concentration correlated with clinical outcomes in patients treated with abatacept or adalimumab on background methotrexate (MTX) in the 2-year AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE rheumatoid arthritis subjects with background MTX) study. In this exploratory analysis, anti-CCP2 antibody concentration was measured at baseline, and antibody-positive patients were divided into equal quartiles, Q1-Q4, representing increasing antibody concentrations. Clinical outcomes analysed by baseline anti-CCP2 status and quartile included change from baseline in disease activity and disability and remission rates. Baseline characteristics were generally comparable across quartiles and treatment groups. In both treatment groups, anti-CCP2 antibody-negative patients responded less well than antibody-positive patients. At year 2, improvements in disease activity and disability and remission rates were similar across Q1-Q3, but were numerically higher in Q4 in the abatacept group; in contrast, treatment effects were similar across all quartiles in the adalimumab group. In AMPLE, baseline anti-CCP2 positivity was associated with a better response for abatacept and adalimumab. Patients with the highest baseline anti-CCP2 antibody concentrations had better clinical response with abatacept than patients with lower concentrations, an association that was not observed with adalimumab. NCT00929864. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. A CLEC16A variant confers risk for juvenile idiopathic arthritis and anti-cyclic citrullinated peptide antibody negative rheumatoid arthritis.

    PubMed

    Skinningsrud, Beate; Lie, Benedicte A; Husebye, Eystein S; Kvien, Tore K; Førre, Øystein; Flatø, Berit; Stormyr, Alice; Joner, Geir; Njølstad, Pål R; Egeland, Thore; Undlien, Dag E

    2010-08-01

    Variants in CLEC16A have conferred susceptibility to autoimmune diseases in genome-wide association studies. The present work aimed to investigate the locus' involvements in juvenile idiopathic arthritis (JIA) and further explore the association with rheumatoid arthritis (RA), type 1 diabetes (T1D) and Addison's disease (AD) in the Norwegian population. Three single nucleotide polymorphisms (SNPs) were genotyped in patients with RA (n=809), JIA (n=509), T1D (n=1211) and AD (n=414) and in healthy controls (n=2149). All diseases were associated with CLEC16A, but with different SNPs. The intron 22 SNP, rs6498169, was associated with RA (p=0.006) and JIA (p=0.016) and the intron 19 SNPs, rs12708716/rs12917716, with T1D (p=1x10-5) and AD (p=2x10-4). The RA association was confined to the anti-cyclic citrullinated peptide antibody (anti-CCP) negative subgroup (p=2x10-4). This is the first report of a CLEC16A association with JIA and a split of the RA association according to anti-CCP status. Different causative variants underlie the rheumatic versus the organ specific diseases.

  10. Aedes aegypti anti-salivary gland antibody concentration and dengue virus exposure history in healthy individuals living in an endemic area in Colombia.

    PubMed

    Londoño-Rentería, Berlín; Cárdenas, Jenny C; Giovanni, Jennifer E; Cárdenas, Lucio; Villamizar, Paloma; Rolón, Jennifer; Chisenhall, Daniel M; Christofferson, Rebecca C; Carvajal, Daisy J; Pérez, Omar G; Wesson, Dawn M; Mores, Christopher N

    2015-01-01

    Mosquito salivary proteins are able to induce an antibody response that reflects the level of human-vector contact. IgG antibodies against dengue virus (DENV-IgG) are indicators of previous exposure. The risk of DENV transmission is not only associated to mosquito or dengue factors, but also to socioeconomic factors that may play an important role in the disease epidemiology. To determine the effect of the presence of Aedes aegypti mosquitos in different stages in households and the history of dengue exposure on vector-human contact determined by the level of anti-salivary protein antibodies in people living in a Colombian endemic area. A pilot study of 58 households and 55 human subjects was conducted in Norte de Santander, Colombia. A questionnaire for socioeconomic factors was administered and houses were examined for the presence of Ae. aegypti specimens in the aquatic stages. The level of DENV-IgG antibodies (DENV-IgG), in addition to IgG and IgM anti- Ae. aegypti salivary gland extract (SGE) antibodies (SGE-IgG, SGE-IgM) were evaluated by ELISA using blood collected in filter paper. We found a significant higher level of SGE-IgG antibodies in subjects living in houses with Ae. aegypti in aquatic stages. We also found a higher concentration of SGE-IgG antibodies in people exposed to DENV, a positive correlation between IgM-SGE and IgG-DENV and a negative correlation with IgG-SGE. Anti-salivary proteins antibodies are consistent with the presence of Ae. aegypti aquatic stages inside houses and DENV-IgG antibodies concentrations.

  11. Fabrication of MoS2 biosensor to detect lower-concentrated area of biological molecules(Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Yang, Erika; Ryu, Byunghoon; Nam, Hongsuk; Liang, Xiaogan

    2017-03-01

    Two dimensional layered transition metal dichalcogenides (TMDC) materials have the growing potential to upstage graphene in the next generation of biosensors in detecting lower-concentrated areas of biomolecules. The current gold-standard detection method is the enzyme-linked immunosorbent assay (ELISA), an immunological assay technique that makes use of an enzyme bonded to a particular antibody or antigen. However, this technique is not only bulky, labor-intensive, and time extensive, but more importantly, the ELISA has relatively low detection limits of only 600 femtomolar (fM). In this work, for the first time, we present a novel flexible, sensitive MoS2 (molybdenum disulfide) biosensor, as shown in Figure 1, composed of few-layer of MoS2 as the channel material, and flexible polyimide as the substrate. In order to nano-fabricate this flexible biosensor, we mechanically transferred a few layers of MoS2 onto the flexible substrate polyimide and photolithography to create a patterning on the surface, and as a result, we were able to create a transistor that used MoS2 as its conductance channel. We successfully fabricated this MoS2 biosensor onto a flexible polyimide substrate. Furthermore, the fabricated flexible MoS2 biosensor can be utilized for quantifying the time-dependent reaction kinetics of streptavidin-biotin binding. Figure 2 shows the transfer characteristics of flexible MoS2 biosensors measured under different concentrations of streptavidin. The flexible MoS2 biosensor could illustrate a faster detection time in matters of minutes, and higher sensitivity with detection limits as low as 10 fM. Time versus equilibrium constants will be presented in details.

  12. Real-time monitoring the distribution of antibody-photo-absorber conjugates during photoimmunotherapy in vivo(Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Tang, Qinggong; Lin, Jonathan; Nagaya, Tadanobu; Liu, Yi; Kobayashi, Hisataka; Chen, Yu

    2017-02-01

    Photo-immunotherapy (PIT) is an emerging low-side-effect cancer therapy based on monoclonal antibody (mAb) conjugated with a near-infrared (NIR) phthalocyanine dye IRDye700DX (IR700 is not only fluorescent which can be used as an imaging agent, but also phototoxic) that induces rapid cell death after exposure to NIR light. PIT induces highly-selective cancer cell death while leaving most of tumor blood vessels unharmed, leading to an effect termed super-enhanced permeability and retention (SUPR), which significantly improve the effectiveness of anti-cancer drug. Currently, the therapeutic effects of PIT were monitored using IR700 fluorescent signal based on macroscopic fluorescence reflectance imager, which lacks the resolution and depth information to reveal the intra-tumor heterogeneity of mAb-IR700 distribution. We developed a minimally-invasive two-channel fluorescence fiber imaging system by combining the traditional fluorescence imaging microscope with two imaging fiber bundles ( 0.85 mm) to monitor mAb-IR700 distribution and therapeutic effects during PIT at different intra-tumor locations (e.g. tumor periphery vs. tumor rim) in situ and in real time simutaneously, thereby enabling evaluation of the therapeutic effects in vivo and optimization of treatment regimens accordingly. Experiments were carried out on ten mice. The average fluorescence intensity recovery after PIT in tumor rim is 91.50% while 100.63% in tumor periphery. Significantly higher fluorescence redistribution (P=0.0371) in tumor periphery than tumor rim after PIT treatment were observed. In order to verify the results, two-photon microscopy combining with micro-prism was also used to record the mAb-IR700 distribution at different depth locations of the tumor during PIT.

  13. Symptoms, spirometry, and serum antibody concentrations among compost workers exposed to organic dust.

    PubMed

    van Kampen, Vera; Deckert, Anja; Hoffmeyer, Frank; Taeger, Dirk; Brinkmann, Elmar; Brüning, Thomas; Raulf-Heimsoth, Monika; Bünger, Jürgen

    2012-01-01

    Work-related symptoms and diseases of 190 currently exposed compost workers, 59 former compost workers, and 38 nonexposed control subjects were investigated in a cross-sectional study. Using a standardized questionnaire, participants were asked for work-related symptoms, exposures to bioaerosols, atopic diseases, and smoking habits. The subjects underwent a physical examination and a lung function test. In addition, total immunoglobulin (Ig) E, IgE specific to environmental allergens and moulds, and IgG specific to molds and actinomycetes were quantified. Compared to controls, compost workers suffered more often from cough and irritation of the eyes in terms of mucosal membrane irritation (MMI). Former compost workers reported similar work-related complaints, but most MMI symptoms had improved after termination of bioaerosol exposure. In contrast, cough and dyspnea persisted, indicating a chronic process. Lung function parameters of compost workers were within the reference ranges. Nevertheless, forced vital capacity (FVC) was significantly lower than for controls. Specific IgE to environmental allergens and molds was positive in 25.3% and 7.4%, respectively, of currently exposed compost workers. There were no marked differences in IgE and IgG concentrations among the three groups. Compost workers suffered with a higher frequency from cough and MMI symptoms. The findings that MMI symptoms improved in former compost workers after leaving the job confirmed the association with bioaerosol exposure. Further, the reduced FVC may be produced by this exposure. There was no higher frequency of mold sensitization in the group of compost workers compared to controls, which may be an indication of a healthy worker survivor effect.

  14. The molecular weight and concentration of dextran sulfate affect cell growth and antibody production in CHO cell cultures.

    PubMed

    Hyoung Park, Jin; Sin Lim, Myung; Rang Woo, Ju; Won Kim, Jong; Min Lee, Gyun

    2016-09-01

    To investigate the effect of dextran sulfate (DS), a widely used anti-aggregation agent, on cell growth and monoclonal antibody (mAb) production including the quality attributes, DS with the three different MWs (4,000 Da, 15,000 Da, and 40,000 Da) at various concentrations (up to 1 g/L) was added to suspension cultures of two different recombinant CHO (rCHO) cell lines producing mAb, SM-0.025 and CS13-1.00. For both cell lines, the addition of DS, regardless of the MW and concentration of DS used, improved cell growth and viability in the decline phase of growth. However, it increased mAb production only in the CS13-1.00 cells. Among the three different MWs, 40,000 Da DS was most effective in attenuating cell aggregation during the cultures of CS13-1.00 cells, and showed the highest maximum mAb concentration. For SM-0.025 cells, it significantly decreased specific mAb productivity, particularly at a high concentration of DS. Overall, DS addition did not negatively affect the quality attributes of mAbs (aggregation, charge variation, and glycosylation), though its efficacy on mAb quality depended on the MW and concentration of DS and cell lines. For both cell lines, the addition of DS did not affect N-glycosylation of mAbs and decreased basic charge variants in mAbs. For CS13-1.00 cells, the mAb monomer increased with the addition of 40,000 Da DS at 0.3-1.0 g/L. Taken together, to maximize the beneficial effect of DS addition on mAb production, the optimal MW and concentration of DS should be determined for each specific rCHO cell line. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1113-1122, 2016. © 2016 American Institute of Chemical Engineers.

  15. On the role of salt type and concentration on the stability behavior of a monoclonal antibody solution.

    PubMed

    Arosio, Paolo; Jaquet, Baptiste; Wu, Hua; Morbidelli, Massimo

    2012-07-01

    Protein-salt interactions regulate protein solubility and stability and in particular several protein related processes, such as salting-out and aggregation. Using an IgG2 monoclonal antibody as a model multi-domain therapeutic protein, we have investigated the salt effect on the reversible formation of protein clusters with small aggregation number. The oligomer formation has been quantified by size exclusion chromatography (SEC). It is found that the salt effect is strongly ion specific and pH dependent. In particular, at pH 3.0 only anions affect the aggregation propensity, while at pH 4.0 both anions and cations influence the aggregation rate. The ranking of the anion effect follows the Hofmeister series with the only exception of sulfate, while that of the cation effect does not. In addition, a maximum of the aggregation propensity as a function of salt concentration is observed (i.e., presence of re-stabilization). By correlating the aggregation kinetics to the experimental investigation of protein structure and surface energy, it is shown that changes in pH and salt concentration induce aggregation not only through charge screening and various solvation forces, but also through the formation of protein intermediates characterized by partially ordered structures and certain degrees of hydrophobicity. The complex interaction between the solvation forces and such protein secondary structures induced by salts explains the observed experimental results relative to re-stabilization at large salt concentrations, ion specificity and the peculiar behavior of the sulfate anion.

  16. Sub-inhibitory concentrations of human α-defensin potentiate neutralizing antibodies against HIV-1 gp41 pre-hairpin intermediates in the presence of serum.

    PubMed

    Demirkhanyan, Lusine; Marin, Mariana; Lu, Wuyuan; Melikyan, Gregory B

    2013-01-01

    Human defensins are at the forefront of the host responses to HIV and other pathogens in mucosal tissues. However, their ability to inactivate HIV in the bloodstream has been questioned due to the antagonistic effect of serum. In this study, we have examined the effect of sub-inhibitory concentrations of human α-defensin HNP-1 on the kinetics of early steps of fusion between HIV-1 and target cells in the presence of serum. Direct measurements of HIV-cell fusion using an enzymatic assay revealed that, in spite of the modest effect on the extent of fusion, HNP-1 prolonged the exposure of functionally important transitional epitopes of HIV-1 gp41 on the cell surface. The increased lifetime of gp41 intermediates in the presence of defensin was caused by a delay in the post-coreceptor binding steps of HIV-1 entry that correlated with the marked enhancement of the virus' sensitivity to neutralizing anti-gp41 antibodies. By contrast, the activity of antibodies to gp120 was not affected. HNP-1 appeared to specifically potentiate antibodies and peptides targeting the first heptad repeat domain of gp41, while its effect on inhibitors and antibodies to other gp41 domains was less prominent. Sub-inhibitory concentrations of HNP-1 also promoted inhibition of HIV-1 entry into peripheral blood mononuclear cells by antibodies and, more importantly, by HIV-1 immune serum. Our findings demonstrate that: (i) sub-inhibitory doses of HNP-1 potently enhance the activity of a number of anti-gp41 antibodies and peptide inhibitors, apparently by prolonging the lifetime of gp41 intermediates; and (ii) the efficiency of HIV-1 fusion inhibitors and neutralizing antibodies is kinetically restricted. This study thus reveals an important role of α-defensin in enhancing adaptive immune responses to HIV-1 infection and suggests future strategies to augment these responses.

  17. Glycans Flanking the Hypervariable Connecting Peptide between the A and B Strands of the V1/V2 Domain of HIV-1 gp120 Confer Resistance to Antibodies That Neutralize CRF01_AE Viruses

    PubMed Central

    O’Rourke, Sara M.; Sutthent, Ruengpung; Phung, Pham; Mesa, Kathryn A.; Frigon, Normand L.; To, Briana; Horthongkham, Navin; Limoli, Kay; Wrin, Terri; Berman, Phillip W.

    2015-01-01

    Understanding the molecular determinants of sensitivity and resistance to neutralizing antibodies is critical for the development of vaccines designed to prevent HIV infection. In this study, we used a genetic approach to characterize naturally occurring polymorphisms in the HIV envelope protein that conferred neutralization sensitivity or resistance. Libraries of closely related envelope genes, derived from virus quasi-species, were constructed from individuals infected with CRF01_AE viruses. The libraries were screened with plasma containing broadly neutralizing antibodies, and neutralization sensitive and resistant variants were selected for sequence analysis. In vitro mutagenesis allowed us to identify single amino acid changes in three individuals that conferred resistance to neutralization by these antibodies. All three mutations created N-linked glycosylation sites (two at N136 and one at N149) proximal to the hypervariable connecting peptide between the C-terminus of the A strand and the N-terminus of the B strand in the four-stranded V1/V2 domain β-sheet structure. Although N136 has previously been implicated in the binding of broadly neutralizing monoclonal antibodies, this glycosylation site appears to inhibit the binding of neutralizing antibodies in plasma from HIV-1 infected subjects. Previous studies have reported that the length of the V1/V2 domain in transmitted founder viruses is shorter and possesses fewer glycosylation sites compared to viruses isolated from chronic infections. Our results suggest that vaccine immunogens based on recombinant envelope proteins from clade CRF01_AE viruses might be improved by inclusion of envelope proteins that lack these glycosylation sites. This strategy might improve the efficacy of the vaccines used in the partially successful RV144 HIV vaccine trial, where the two CRF01_AE immunogens (derived from the A244 and TH023 isolates) both possessed glycosylation sites at N136 and N149. PMID:25793890

  18. Glycans flanking the hypervariable connecting peptide between the A and B strands of the V1/V2 domain of HIV-1 gp120 confer resistance to antibodies that neutralize CRF01_AE viruses.

    PubMed

    O'Rourke, Sara M; Sutthent, Ruengpung; Phung, Pham; Mesa, Kathryn A; Frigon, Normand L; To, Briana; Horthongkham, Navin; Limoli, Kay; Wrin, Terri; Berman, Phillip W

    2015-01-01

    Understanding the molecular determinants of sensitivity and resistance to neutralizing antibodies is critical for the development of vaccines designed to prevent HIV infection. In this study, we used a genetic approach to characterize naturally occurring polymorphisms in the HIV envelope protein that conferred neutralization sensitivity or resistance. Libraries of closely related envelope genes, derived from virus quasi-species, were constructed from individuals infected with CRF01_AE viruses. The libraries were screened with plasma containing broadly neutralizing antibodies, and neutralization sensitive and resistant variants were selected for sequence analysis. In vitro mutagenesis allowed us to identify single amino acid changes in three individuals that conferred resistance to neutralization by these antibodies. All three mutations created N-linked glycosylation sites (two at N136 and one at N149) proximal to the hypervariable connecting peptide between the C-terminus of the A strand and the N-terminus of the B strand in the four-stranded V1/V2 domain β-sheet structure. Although N136 has previously been implicated in the binding of broadly neutralizing monoclonal antibodies, this glycosylation site appears to inhibit the binding of neutralizing antibodies in plasma from HIV-1 infected subjects. Previous studies have reported that the length of the V1/V2 domain in transmitted founder viruses is shorter and possesses fewer glycosylation sites compared to viruses isolated from chronic infections. Our results suggest that vaccine immunogens based on recombinant envelope proteins from clade CRF01_AE viruses might be improved by inclusion of envelope proteins that lack these glycosylation sites. This strategy might improve the efficacy of the vaccines used in the partially successful RV144 HIV vaccine trial, where the two CRF01_AE immunogens (derived from the A244 and TH023 isolates) both possessed glycosylation sites at N136 and N149.

  19. Detection of aqueous VEGF concentrations before and after intravitreal injection of anti-VEGF antibody using low-volume sampling paper-based ELISA.

    PubMed

    Hsu, Min-Yen; Hung, Yu-Chien; Hwang, De-Kuang; Lin, Shang-Chi; Lin, Keng-Hung; Wang, Chun-Yuan; Choi, Hin-Yeung; Wang, Yu-Ping; Cheng, Chao-Min

    2016-10-11

    Intraocular vascular endothelial growth factor (VEGF) levels play an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Here, we aimed to develop a paper-based enzyme-linked immunosorbent assay (P-ELISA) to analyze the suppression of aqueous VEGF concentrations following intravitreal injection (IVI) of anti-VEGF antibody (bevacizumab or ranibizumab). A total of 25 eyes with wet AMD, one with myopic neovascularization, and one with polypoidal choroidal vasculopathy were enrolled in this study. The limit of detection using P-ELISA was 0.03 pg/mL. Forty-six consecutive samples of aqueous humor were acquired. From all samples, 66.67% (10/15) achieved complete VEGF suppression (below the detection limit) within 5 weeks of receiving IVI of anti-VEGF antibody. Only 13.33% of samples (2/15) achieved complete VEGF suppression 5 weeks after receiving treatment. In some patients, elevated VEGF was still detected 5 weeks after receipt of anti-VEGF antibody, and all samples (10/10) were found to have elevated VEGF levels 49 days after treatment. Thus, we suggest that monthly IVI of anti-VEGF antibody may be required to ensure durable VEGF inhibition. Ultrasensitive P-ELISA can detect elevated VEGF at an earlier time point and may facilitate decision-making regarding appropriate treatment strategies.

  20. Detection of aqueous VEGF concentrations before and after intravitreal injection of anti-VEGF antibody using low-volume sampling paper-based ELISA

    PubMed Central

    Hsu, Min-Yen; Hung, Yu-Chien; Hwang, De-Kuang; Lin, Shang-Chi; Lin, Keng-Hung; Wang, Chun-Yuan; Choi, Hin-Yeung; Wang, Yu-Ping; Cheng, Chao-Min

    2016-01-01

    Intraocular vascular endothelial growth factor (VEGF) levels play an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Here, we aimed to develop a paper-based enzyme-linked immunosorbent assay (P-ELISA) to analyze the suppression of aqueous VEGF concentrations following intravitreal injection (IVI) of anti-VEGF antibody (bevacizumab or ranibizumab). A total of 25 eyes with wet AMD, one with myopic neovascularization, and one with polypoidal choroidal vasculopathy were enrolled in this study. The limit of detection using P-ELISA was 0.03 pg/mL. Forty-six consecutive samples of aqueous humor were acquired. From all samples, 66.67% (10/15) achieved complete VEGF suppression (below the detection limit) within 5 weeks of receiving IVI of anti-VEGF antibody. Only 13.33% of samples (2/15) achieved complete VEGF suppression 5 weeks after receiving treatment. In some patients, elevated VEGF was still detected 5 weeks after receipt of anti-VEGF antibody, and all samples (10/10) were found to have elevated VEGF levels 49 days after treatment. Thus, we suggest that monthly IVI of anti-VEGF antibody may be required to ensure durable VEGF inhibition. Ultrasensitive P-ELISA can detect elevated VEGF at an earlier time point and may facilitate decision-making regarding appropriate treatment strategies. PMID:27725716

  1. Recombinant NDV expressing cytokines or fliC confers a quick immune response against NDV challenge and resistance to maternal antibody.

    PubMed

    Zhang, Tianyuan; Liu, Yunye; Wang, Hui; Zhang, Xu; Zhu, Shenglong; Xu, Pengfei; Yin, Jiechao; Ren, Guiping; Liu, Jingli; Li, Deshan

    2016-11-30

    Currently, there are two major bottleneck problems which seriously affect prevention of the Newcastle disease (ND): interference of maternal antibody on NDV vaccination and slow production of neutralization antibody. To overcome these problems, in present study, four rNDV vaccine strains expressing bio-adjuvants chIL2, chIL15, chGM-CSF or fliC gene were constructed and rescued using reverse genetics approach. The HI antibody titers of SPF birds immunized with rNDV reached to 5.5log2, 4.7log2, 6.5log2 and 5.8log2, respectively at the 8th day post immunization, while the antibody titers of the parental virus and control were 3.3log2 and 1log2, respectively. The immunized chickens were challenged by 10(4)ELD50 dose of the virulent NDV BJ strains at the 7th day post immunization. The protection rate of the four rNDVs bio-adjuvant groups was 100%, while the protection rate of the parental group was 80%. We also examined the anti-maternal antibody activity of these adjuvant vaccines by detection HI titer after vaccination of chickens with high (8.4log2) or low (5log2) maternal antibody levels. In chicken flock with higher maternal antibody, parental strain could not resist the influence of the maternal antibody and induce any notable change of HI antibody kinetics. However, both rClon30-chGM-CSF and rClon30-flic were able to resist the influence of the maternal antibody and maintained the HI antibody above the protection level during the 14day's experiment. In chicken flock with lower maternal antibody, the parental rclone30 strain could not induce HI titer to the protection level until the 14th day, but both rClon30-GM-CSF and clone30-fliC raised the HI antibody to above the protection level at the 7th day post vaccination.

  2. A stable cytosolic expression of VH antibody fragment directed against PVY NIa protein in transgenic potato plant confers partial protection against the virus.

    PubMed

    Bouaziz, Donia; Ayadi, Malika; Bidani, Amira; Rouis, Souad; Nouri-Ellouz, Oumèma; Jellouli, Raïda; Drira, Noureddine; Gargouri-Bouzid, Radhia

    2009-04-01

    The expression of recombinant antibodies in transgenic plants has been proved to be an efficient approach for large-scale production. However, the stability of these molecules and their accumulation level depend on their molecular properties and cellular targeting. The expression of single-domain antibody fragment (VH) can be advantageous since it offers small length, high expression, solubility and stability. It can therefore be preferred to other antibody derivatives avoiding the expression difficulties related to immunoglobulin domain folding via the formation of disulfide bridge. This report describes the production of transgenic potato plants expressing a VH antibody directed against the NIa protease of potato virus Y. The antibody was driven by the constitutive CaMV 35S RNA promoter. The expression cassette was transferred into potato plants via Agrobacterium tumefaciens mediated transformation. All transgenic lines showed detectable levels of VH protein confirming the efficient translation and stability of this protein. The cellular localisation of the VH antibody was investigated. Transgenic and control plants were transferred in the greenhouse and mechanically inoculated by PVY(o) suspension. Some of the transgenic lines showed delayed symptoms at the first period post inoculation and then displayed a recovery phenomenon while the virions were still detected in the leaves.

  3. Identification of regulated genes conferring resistance to high concentrations of glyphosate in a new strain of Enterobacter.

    PubMed

    Fei, Yun-Yan; Gai, Jun-Yi; Zhao, Tuan-Jie

    2013-12-01

    Glyphosate is a widely used herbicide that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) activity. Most plants and microbes are sensitive to glyphosate. However, transgenic-resistant crops that contain a modified epsps obtained from the resistant microbes have been commercially successful and therefore, new resistance genes and their adaptive regulatory mechanisms are of great interest. In this study, a soil-borne, glyphosate-resistant bacterium was selected and identified as Enterobacter. The EPSPS in this strain was found to have been altered to a resistant one. A total of 42 differentially expressed genes (DEGs) in the glyphosate were screened using microarray techniques. Under treatment, argF, sdhA, ivbL, rrfA-H were downregulated, whereas the transcripts of speA, osmY, pflB, ahpC, fusA, deoA, uxaC, rpoD and a few ribosomal protein genes were upregulated. Data were verified by quantitative real-time PCR on selected genes. All transcriptional changes appeared to protect the bacteria from glyphosate and associated osmotic, acidic and oxidative stresses. Many DEGs may have the potential to confer resistance to glyphosate alone, and some may be closely related to the shikimate pathway, reflecting the complex gene interaction network for glyphosate resistance. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  4. Numerical analysis on using compound parabolic couplers for direct transmission of concentrated solar radiation via optical fibre (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Rahou, Maryam; Andrews, John; Rosengarten, Gary

    2016-09-01

    A challenge in high-temperature solar thermal applications is transfer of concentrated solar radiation to the load with minimum energy loss. The use of a solar concentrator in conjunction with optical fibres has potential advantages in terms of transmission efficiency, technical feasibility and cost-effectiveness compared to a conventional heat transfer system employing heat exchangers and a heat transfer fluid. For transferring higher levels of concentrated flux it is necessary to employ multiple optical fibres or fibre bundles. However, the losses at the incident plane of a bundle due to absorption by the epoxy and cladding between the individual fibres in a bundle are substantial, typically over 60% of the overall transmission loss. The optical transmission of the system can thus be enhanced by employing a coupler between the concentrated solar radiation and the entrance to the bundle that reflects all incident light into the cores of individual fibres rather than allowing it to strike the interstitial spaces between the cores. This paper describes the design for such couplers based on multiple compound parabolic (CP) reflectors each with its exit aperture coinciding with the core of an individual fibre within the bundle. The proposed design employs external reflection from a machined metallic aluminium surface. This CP arrangement has the additional benefit of increasing the concentration ratio of the primary solar concentrator used. Simulation modeling using LightTools is conducted into a parabolic Cassegrain solar concentrator employing these CP couplers prior to a fibre bundle. The dependence of overall transmission and total optical efficiency of the system over lengths of the bundle up to 100 m are investigated quantitatively. In addition, the influence on transmission of the angular distribution of radiation intensity at the aperture of the couplers is studied.

  5. Randomized Cross-Sectional Study to Compare HIV-1 Specific Antibody and Cytokine Concentrations in Female Genital Secretions Obtained by Menstrual Cup and Cervicovaginal Lavage

    PubMed Central

    Archary, Derseree; Liebenberg, Lenine J.; Werner, Lise; Tulsi, Sahil; Majola, Nelisile; Naicker, Nivashnee; Dlamini, Sarah; Hope, Thomas J.; Samsunder, Natasha; Abdool Karim, Salim S.; Morris, Lynn; Passmore, Jo-Ann S.; Garrett, Nigel J.

    2015-01-01

    Introduction Optimizing methods for genital specimen collection to accurately characterize mucosal immune responses is a priority for the HIV prevention field. The menstrual cup (MC) has been proposed as an alternative to other methods including cervicovaginal lavage (CVL), but no study has yet formally compared these two methods. Methods Forty HIV-infected, antiretroviral therapy-naïve women from the CAPRISA 002 acute HIV infection cohort study were randomized to have genital fluid collected using the MC with subsequent CVL, or by CVL alone. Qualitative data, which assessed levels of comfort and acceptability of MC using a 5-point Likert scale, was collected. Luminex multiplex assays were used to measure HIV-specific IgG against multiple gene products and 48 cytokines. Results The majority (94%) of participants indicated that insertion, wearing and removal of the MC was comfortable. Nineteen MCs with 18 matching, subsequent CVLs and 20 randomized CVLs were available for analysis. Mucosal IgG responses against four HIV-antigens were detected in 99% of MCs compared to only 80% of randomized CVLs (p = 0.029). Higher specific antibody activity and total antibodies were observed in MCs compared to CVL (all p<0.001). In MCs, 42/48 (88%) cytokines were in the detectable range in all participants compared to 27/48 (54%) in CVL (p<0.001). Concentrations of 22/41 cytokines (53.7%) were significantly higher in fluid collected by MC. Both total IgG (r = 0.63; p = 0.005) and cytokine concentrations (r = 0.90; p<0.001) correlated strongly between MC and corresponding post-MC CVL. Conclusions MC sampling improves the detection of mucosal cytokines and antibodies, particularly those present at low concentrations. MC may therefore represent an ideal tool to assess immunological parameters in genital secretions, without interfering with concurrent collection of conventional CVL samples. PMID:26147923

  6. Application of Photonic Crystal Enhanced Fluorescence to Detection of Low Serum Concentrations of Human IgE Antibodies Specific for a Purified Cat Allergen (Fel d1)

    PubMed Central

    Tan, Yafang; Halsey, John F.; Tang, Tiantian; Wetering, Scott Vande; Taine, Elaine; Van Cleve, Mark; Cunningham, Brian T.

    2015-01-01

    We demonstrate the detection of low concentrations of allergen-specific Immunoglobulin E (IgE) in human sera using a Photonic Crystal Enhanced Fluorescence (PCEF) microarray platform. The Photonic Crystal (PC) surface, designed to provide optical resonances for the excitation wavelength and emission wavelength of Cy5, was used to amplify the fluorescence signal intensity measured from a multiplexed allergen microarray. Surface-based sandwich immunoassays were used to detect and quantify specific IgE antibodies against a highly purified cat allergen (Fel d1). A comparison of the lowest detectable concentration of IgE measured by the PC microarray system and a commercially available clinical analyzer demonstrated that the PCEF microarray system provides higher sensitivity. The PCEF system was able to detect low concentrations of specific IgE (~0.02 kU/L), which is 5 to 17 -fold more sensitive than the commercially available FDA-approved analyzers. In preliminary experiments using multi-allergen arrays, we demonstrate selective simultaneous detection of IgE antibodies to multiple allergens. PMID:26406461

  7. Measurement of cyclosporine concentrations in whole blood: HPLC and radioimmunoassay with a specific monoclonal antibody and /sup 3/H- or /sup 125/I-labeled ligand compared

    SciTech Connect

    Wolf, B.A.; Daft, M.C.; Koenig, J.W.; Flye, M.W.; Turk, J.W.; Scott, M.G.

    1989-01-01

    We compared cyclosporine concentrations in whole blood as measured by HPLC and by RIA with a monoclonal antibody specific for cyclosporine with /sup 3/H- or /sup 125/I-labeled cyclosporine ligand. The /sup 3/H-RIA kit slightly underestimated cyclosporine concentrations (greater than 600 micrograms/L) in comparison with HPLC. Over a wide range of concentrations, cyclosporine measured with the /sup 125/I-RIA kit correlated well with HPLC (slope = 0.99, n = 301, r = 0.98), observed for samples from recipients of kidney, heart, or liver allografts (respective slopes: 1.01, 0.93, and 1.00). The /sup 125/I-RIA standard curve was linear to 1000 micrograms of cyclosporine per liter. Inter- and intra-assay CVs for /sup 125/I-RIA measurements of cyclosporine were less than or equal to 7%. Evidently, the /sup 125/I-RIA kit involving a monoclonal antibody specific for cyclosporine is equivalent to the HPLC assay and can replace it for therapeutic drug monitoring of cyclosporine therapy.

  8. Application of photonic crystal enhanced fluorescence to detection of low serum concentrations of human IgE antibodies specific for a purified cat allergen (Fel D1).

    PubMed

    Tan, Yafang; Halsey, John F; Tang, Tiantian; Wetering, Scott Vande; Taine, Elaine; Cleve, Mark Van; Cunningham, Brian T

    2016-03-15

    We demonstrate the detection of low concentrations of allergen-specific Immunoglobulin E (IgE) in human sera using a Photonic Crystal Enhanced Fluorescence (PCEF) microarray platform. The Photonic Crystal (PC) surface, designed to provide optical resonances for the excitation wavelength and emission wavelength of Cy5, was used to amplify the fluorescence signal intensity measured from a multiplexed allergen microarray. Surface-based sandwich immunoassays were used to detect and quantify specific IgE antibodies against a highly purified cat allergen (Fel d1). A comparison of the lowest detectable concentration of IgE measured by the PC microarray system and a commercially available clinical analyzer demonstrated that the PCEF microarray system provides higher sensitivity. The PCEF system was able to detect low concentrations of specific IgE (~0.02 kU/L), which is 5-17-fold more sensitive than the commercially available FDA-approved analyzers. In preliminary experiments using multi-allergen arrays, we demonstrate selective simultaneous detection of IgE antibodies to multiple allergens.

  9. Neutralization of Diverse Human Cytomegalovirus Strains Conferred by Antibodies Targeting Viral gH/gL/pUL128-131 Pentameric Complex

    PubMed Central

    Ha, Sha; Li, Fengsheng; Troutman, Matthew C.; Freed, Daniel C.; Tang, Aimin; Loughney, John W.; Wang, I-Ming; Vlasak, Josef; Nickle, David C.; Rustandi, Richard R.; Hamm, Melissa; DePhillips, Pete A.; Zhang, Ningyan; McLellan, Jason S.; Zhu, Hua; Adler, Stuart P.; McVoy, Michael A.; An, Zhiqiang

    2017-01-01

    ABSTRACT Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a vaccinated animal, we mapped eight sites on the dominant virus-neutralizing antigen—the pentameric complex of glycoprotein H (gH), gL, and pUL128, pUL130, and pUL131. By evaluating the site-specific antibodies in vaccine immune sera, we demonstrated that vaccination elicited functional antiviral antibodies to multiple neutralizing sites in rhesus macaques, with quality attributes comparable to those of CMV hyperimmune globulin. Furthermore, these immune sera showed antiviral activities against a panel of genetically distinct HCMV clinical isolates. These results highlighted the importance of understanding the quality of vaccine-induced antibody responses, which includes not only the neutralizing potency in key cell types but also the ability to protect against the genetically diverse field strains. IMPORTANCE HCMV is the leading cause of congenital viral infection, and development of a preventive vaccine is a high public health priority. To understand the strain coverage of vaccine-induced immune responses in comparison with natural immunity, we used a panel of broadly neutralizing antibodies to identify the immunogenic sites of a dominant viral antigen—the pentameric complex. We further demonstrated that following vaccination of a replication

  10. The Impact of Routine HTLV-III Antibody Testing on Public Health. National Institutes of Health Consensus Development Conference Statement, Vol. 6, No. 5.

    ERIC Educational Resources Information Center

    National Institutes of Health (DHHS), Bethesda, MD.

    A policy statement by a group of experts on screening blood donations for contamination by human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS), is presented in this document. This document provides policy recommendations formed by a consensus conference sponsored by the National Institutes of Health…

  11. Viscosity measurements of antibody solutions by photon correlation spectroscopy: an indirect approach - limitations and applicability for high-concentration liquid protein solutions.

    PubMed

    Wagner, Michael; Reiche, Katharina; Blume, Alfred; Garidel, Patrick

    2013-01-01

    Photon correlation spectroscopy (PCS) is compared with classic rheological measurements using the cone-and-plate technique for the determination of the viscosity of protein solutions. The potential advantages using PCS are small sample volume and fast determination of zero-shear viscosity. The present study assesses potentials and limitations of the applicability of this method for the determination of viscosity of antibody solutions in protein science development. The principle of the assay is based on the determination of the apparent hydrodynamic radius of commercial available latex beads of known size added to protein solutions. Using the Stokes-Einstein equation, the hydrodynamic radius can be converted to viscosity. Several latex particle sizes and concentrations were evaluated and the assay optimized. The PCS assay for viscosity determination was tested using water/glycerol-mixtures, where the viscosity was measured with rheometer using the cone-and-plate method and also compared with published data. Different protein solutions of bovine serum albumin, lysozyme and monoclonal antibodies were then used and the PCS results were compared with viscosity data obtained by the cone-and-plate method. It could be shown that the PCS assay has limitations for the determination of the viscosity of protein solutions, especially monoclonal antibodies. The main reason is due to protein-latex bead interactions leading to the formation of larger aggregates. The use of surface modification of the latex beads can in principle prevent this interaction.

  12. Monitoring of laying capacity, immunoglobulin Y concentration, and antibody titer development in chickens immunized with ricin and botulinum toxins over a two-year period.

    PubMed

    Pauly, D; Dorner, M; Zhang, X; Hlinak, A; Dorner, B; Schade, R

    2009-02-01

    One of the key benefits in using chickens for immunization is the high yield of antibodies obtainable. It is known that egg production decreases over time, while animal maintenance costs remain stable. It would, however, be desirable to keep hens as long as possible to obtain maximal amounts of antibodies. To identify a suitable length of time that animals can be kept and to optimize the cost:yield ratio, we monitored the number of eggs laid, the total amount of chicken IgY, and the specific antibody titer from individually prepared eggs over a 2-yr period. The plant toxin ricin and the Clostridium botulinum neurotoxins type A and B were used to immunize 4 chickens. The number of eggs laid in 2 yr was approximately 600 per hen (about 80% of the maximum egg number), yielding about 20 to 40 g of total IgY per hen. A stable antibody titer of 1:100,000 to 1:1,000,000, as measured by ELISA, was obtained following up to 11 injections of 10 to 20 microg of immobilized native toxin. Laying capacities were found to decrease, on average, from 7 eggs/wk at the point of first immunization to 2 eggs/wk after more than 2 yr. In parallel, the yield of total and specific IgY increased over time, so that the antibody recovery remained high, even after prolonged immunization times. Using purified IgY preparations, classical immunological assays such as ELISA and Western blotting were performed. Furthermore, the IgY showed neutralizing capacity when used to block the functional activity of the toxins both in vitro and in vivo. Analysis of the total IgY content over time demonstrated a complex biological oscillation (and the antigen-specific titer), with a shorter time period of around 7 d (circaseptan rhythm). In summary, we successfully immunized chickens with ricin and botulinum neurotoxins and monitored laying capacity, IgY concentration, and specific antibody titer over an extended period of 2 yr.

  13. Small-Angle Neutron Scattering and Neutron Spin Echo Characterization of Monoclonal Antibody Self-Associations at High Concentrations

    NASA Astrophysics Data System (ADS)

    Yearley, Eric; Zarraga, Isidro (Dan); Godfrin, Paul (Doug); Perevozchikova, Tatiana; Wagner, Norman; Liu, Yun

    2013-03-01

    Concentrated therapeutic protein formulations offer numerous delivery and stability challenges. In particular, it has been found that several therapeutic proteins exhibit a large increase in viscosity as a function of concentration that may be dependent on the protein-protein interactions. Small-Angle Neutron Scattering (SANS) and Neutron Spin Echo (NSE) investigations have been performed to probe the protein-protein interactions and diffusive properties of highly concentrated MAbs. The SANS data demonstrate that the inter-particle interactions for a highly viscous MAb at high concentrations (MAb1) are highly attractive, anisotropic and change significantly with concentration while the viscosity and interactions do not differ considerably for MAb2. The NSE results furthermore indicate that MAb1 and MAb2 have strong concentration dependencies of dynamics at high Q that are correlated to the translational motion of the proteins. Finally, it has also been revealed that the individual MAb1 proteins form small clusters at high concentrations in contrast to the MAb2 proteins, which are well-dispersed. It is proposed that the formation of these clusters is the primary cause of the dramatic increase in viscosity of MAb1 in crowded or concentrated environments.

  14. Transgenic Restoration of Urea Transporter A1 Confers Maximal Urinary Concentration in the Absence of Urea Transporter A3.

    PubMed

    Klein, Janet D; Wang, Yanhua; Mistry, Abinash; LaRocque, Lauren M; Molina, Patrick A; Rogers, Richard T; Blount, Mitsi A; Sands, Jeff M

    2016-05-01

    Urea has a critical role in urinary concentration. Mice lacking the inner medullary collecting duct (IMCD) urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) have very low levels of urea permeability and are unable to concentrate urine. To investigate the role of UT-A1 in the concentration of urine, we transgenically expressed UT-A1 in knockout mice lacking UT-A1 and UT-A3 using a construct with a UT-A1 gene that cannot be spliced to produce UT-A3. This construct was inserted behind the original UT-A promoter to yield a mouse expressing only UT-A1 (UT-A1(+/+)/UT-A3(-/-)). Western blot analysis demonstrated UT-A1 in the inner medulla of UT-A1(+/+)/UT-A3(-/-) and wild-type mice, but not in UT-A1/UT-A3 knockout mice, and an absence of UT-A3 in UT-A1(+/+)/UT-A3(-/-) and UT-A1/UT-A3 knockout mice. Immunohistochemistry in UT-A1(+/+)/UT-A3(-/-) mice also showed negative UT-A3 staining in kidney and other tissues and positive UT-A1 staining only in the IMCD. Urea permeability in isolated perfused IMCDs showed basal permeability in the UT-A1(+/+)/UT-A3(-/-) mice was similar to levels in wild-type mice, but vasopressin stimulation of urea permeability in wild-type mice was significantly greater (100% increase) than in UT-A1(+/+)/UT-A3(-/-) mice (8% increase). Notably, basal urine osmolalities in both wild-type and UT-A1(+/+)/UT-A3(-/-) mice increased upon overnight water restriction. We conclude that transgenic expression of UT-A1 restores basal urea permeability to the level in wild-type mice but does not restore vasopressin-stimulated levels of urea permeability. This information suggests that transgenic expression of UT-A1 alone in mice lacking UT-A1 and UT-A3 is sufficient to restore urine-concentrating ability. Copyright © 2016 by the American Society of Nephrology.

  15. Mutations located on both F1 and F2 subunits of the Newcastle disease virus fusion protein confer resistance to neutralization with monoclonal antibodies.

    PubMed Central

    Neyt, C; Geliebter, J; Slaoui, M; Morales, D; Meulemans, G; Burny, A

    1989-01-01

    The fusion gene sequence of six Newcastle disease virus escape mutants revealed that residues important for the integrity of antigenic site 1 and antigenic site 2 were located, respectively, on the F2 subunit and within the cysteine-rich domain of the F1 subunit. We further report the antibody-binding capacity of these mutants. PMID:2463386

  16. Filling of High-Concentration Monoclonal Antibody Formulations into Pre-filled Syringes: Investigating Formulation-Nozzle Interactions To Minimize Nozzle Clogging.

    PubMed

    Shieu, Wendy; Stauch, Oliver B; Maa, Yuh-Fun

    2015-01-01

    Syringe filling of high-concentration/viscosity monoclonal antibody formulations is a complex process that is not fully understood. This study, which builds on a previous investigation that used a bench-top syringe filling unit to examine formulation drying at the filling nozzle tip and subsequent nozzle clogging, further explores the impact of formulation-nozzle material interactions on formulation drying and nozzle clogging. Syringe-filling nozzles made of glass, stainless steel, or plastic (polypropylene, silicone, and Teflon®), which represent a full range of materials with hydrophilic and hydrophobic properties as quantified by contact angle measurements, were used to fill liquids of different viscosity, including a high-concentration monoclonal antibody formulation. Compared with hydrophilic nozzles, hydrophobic nozzles offered two unique features that discouraged formulation drying and nozzle clogging: (1) the liquid formulation is more likely to be withdrawn into the hydrophobic nozzle under the same suck-back conditions, and (2) the residual liquid film left on the nozzle wall when using high suck-back settings settles to form a liquid plug away from the hydrophobic nozzle tip. Making the tip of the nozzle hydrophobic (silicone-coating on glass and Teflon-coating stainless steel) could achieve the same suck-back performance as plastic nozzles. This study demonstrated that using hydrophobic nozzles are most effective in reducing the risk of nozzle clogging by drying of high-concentration monoclonal antibody formulation during extended nozzle idle time in a large-scale filling facility and environment. Syringe filling is a well-established manufacturing process and has been implemented by numerous contract manufacturing organizations and biopharmaceutical companies. However, its technical details and associated critical process parameters are rarely published. Information on high-concentration/viscosity formulation filling is particularly lacking. This

  17. Site-specific antibody-liposome conjugation through copper-free click chemistry: a molecular biology approach for targeted photodynamic therapy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Obaid, Girgis; Wang, Yucheng; Kuriakose, Jerrin; Broekgaarden, Mans; Alkhateeb, Ahmed; Bulin, Anne-Laure; Hui, James; Tsourkas, Andrew; Hasan, Tayyaba

    2016-03-01

    Nanocarriers, such as liposomes, have the ability to potentiate photodynamic therapy (PDT) treatment regimens by the encapsulation of high payloads of photosensitizers and enhance their passive delivery to tumors through the enhanced permeability and retention effect. By conjugating targeting moieties to the surface of the liposomal nanoconstructs, cellular selectivity is imparted on them and PDT-based therapies can be performed with significantly higher dose tolerances, as off-target toxicity is simultaneously reduced.1 However, the maximal benefits of conventional targeted nanocarriers, including liposomes, are hindered by practical limitations including chemical instability, non-selective conjugation chemistry, poor control over ligand orientation, and loss of ligand functionality following conjugation, amongst others.2 We have developed a robust, physically and chemically stable liposomal nanoplatform containing benzoporphyrin derivative photosensitizer molecules within the phospholipid bilayer and an optimized surface density of strained cyclooctyne moieties for `click' conjugation to azido-functionalized antibodies.3 The clinical chimeric anti-EGFR antibody Cetuximab is site-specifically photocrosslinked to a recombinant bioengineered that recognizes the antibody's Fc region, containing a terminal azide.4 The copper-free click conjugation of the bioengineered Cetuximab derivative to the optimized photosensitizing liposome provides exceptional control over the antibody's optimal orientation for cellular antigen binding. Importantly, the reaction occurs rapidly under physiological conditions, bioorthogonally (selectively in the presence of other biomolecules) and without the need for toxic copper catalysis.3 Such state-of-the-art conjugation strategies push the boundaries of targeted photodynamic therapy beyond the limitations of traditional chemical coupling techniques to produce more robust and effective targeted therapeutics with applications beyond

  18. [LEVELS OF SERUM ANTIBODIES TO ENTEROBACTERIAL LIPOPOLYSACCHARIDES AND THEIR RELATIONSHIP WITH CONCENTRATION OF C-REACTIVE PROTEIN IN DIABETES MELLITUS PATIENTS].

    PubMed

    Gordienko, A I

    2015-01-01

    We examined patients with type 1 (DM 1) and type 2 (DM 2) diabetes mellitus. The concentration of C-reactive protein (CRP) in the blood and levels of serum antibodies to different classes of enterobacterial lipopolysaccharides (LPS) were determined by ELISA. Using cluster analysis it was shown that in 40.8% DM-1 patients the increased concentration of CRP is associated with a decrease in the levels of serum anti-LPS-IgA, anti-LPS-IgM and anti-LPS-IgG. In 56.7% of DM-2 patients with increased concentration of CRP levels of serum anti-LPS-IgA and anti-LPS-IgM were not significantly different from the normal values, but the levels of serum anti-LPS-IgG were significantly increased. Activation of inflammation and increase of concentration of the CRP in the blood of DM-2 patients is accompanied by a significant increase in the levels of serum anti-LPS-A and anti-LPS-G, as well as the tendency to reduce the levels of anti-LPS-IgM. The results of this study suggest an association between low intensity inflammation and immune response to enterobacterial LPS in type 1 and 2 diabetes mellitus.

  19. Immunoglobulin Concentrations and Antigen-Specific Antibody Levels in Cervicovaginal Lavages of Rhesus Macaques Are Influenced by the Stage of the Menstrual Cycle

    PubMed Central

    Lü, F. Xusheng; Ma, Zhongmin; Rourke, Tracy; Srinivasan, Seema; McChesney, Michael; Miller, Christopher J.

    1999-01-01

    The levels of antigen-specific antibodies (Abs) and immunoglobulins in the cervical mucus of women vary with the menstrual cycle; the highest levels occur during menses, and the lowest occur during the periovulatory period. The rhesus macaque is a widely used animal model of female genital tract immunity. We sought to determine whether rhesus macaques have a cyclical pattern of changing cervicovaginal Ab and immunoglobulin levels that is similar to that of the human female. This study examined the relationship of the stages of the menstrual cycle to genital mucosal and systemic immunoglobulin concentrations and Ab levels in rhesus macaques. In all seven rhesus macaques studied, the immunoglobulins G and A and some antibodies in cervicovaginal lavages varied with the stages of the menstrual cycle, and in many cases this variation reached the level of statistical significance. In a pattern similar to that of women, the highest levels of Abs and immunoglobulins occurred during menses, and the lowest levels occurred around the time of ovulation. However, the Ab and immunoglobulin levels in serum and rectal lavages did not change with the menstrual cycle stage. The results of this study are consistent with the hypothesis that the ovarian hormones that drive the menstrual cycle influence genital tract immunity in female primates. PMID:10569744

  20. Llama-Derived Single-Chain Antibody Fragments Directed to Rotavirus VP6 Protein Possess Broad Neutralizing Activity In Vitro and Confer Protection against Diarrhea in Mice▿

    PubMed Central

    Garaicoechea, Lorena; Olichon, Aurelien; Marcoppido, Gisela; Wigdorovitz, Andrés; Mozgovoj, Marina; Saif, Linda; Surrey, Thomas; Parreño, Viviana

    2008-01-01

    Group A rotavirus is one of the most common causes of severe diarrhea in human infants and newborn animals. Rotavirus virions are triple-layered particles. The outer capsid proteins VP4 and VP7 are highly variable and represent the major neutralizing antigens. The inner capsid protein VP6 is conserved among group A rotaviruses, is highly immunogenic, and is the target antigen of most immunodiagnosis tests. Llama-derived single-chain antibody fragments (VHH) are the smallest molecules with antigen-binding capacity and can therefore be expected to have properties different from conventional antibodies. In this study a library containing the VHH genes of a llama immunized with recombinant inner capsid protein VP6 was generated. Binders directed to VP6, in its native conformation within the viral particle, were selected and characterized. Four selected VHH directed to conformational epitopes of VP6 recognized all human and animal rotavirus strains tested and could be engineered for their use in immunodiagnostic tests for group A rotavirus detection. Three of the four VHH neutralized rotavirus in vivo independently of the strain serotype. Furthermore, this result was confirmed by in vivo partial protection against rotavirus challenge in a neonatal mouse model. The present study demonstrates for the first time a broad neutralization activity of VP6 specific VHH in vitro and in vivo. Neutralizing VHH directed to VP6 promise to become an essential tool for the prevention and treatment of rotavirus diarrhea. PMID:18632867

  1. Serum Concentration of Anti-TNF Antibodies, Adverse Effects and Quality of Life in Patients with Inflammatory Bowel Disease in Remission on Maintenance Treatment.

    PubMed

    Brandse, Johannan F; Vos, Laura M C; Jansen, Jeroen; Schakel, Toos; Ponsioen, Cyriel I J; van den Brink, Gijs R; D'Haens, Geert R; Löwenberg, Mark

    2015-11-01

    High serum concentrations of infliximab [IFX] and adalimumab [ADA] may be associated with adverse effects in patients with inflammatory bowel disease [IBD]. We aimed to investigate whether high anti-tumour necrosis factor [TNF] trough levels [TLs] were associated with toxicity and impaired quality of life [QoL]. We conducted a prospective cohort study in IBD patients in clinical and biochemical remission on IFX or ADA maintenance therapy. Trough serum concentrations and antidrug antibodies were measured in addition to biochemical markers of inflammation in serum and stool to confirm quiescent disease. QoL was assessed using the Inflammatory Bowel Disease Questionnaire and 36-item short form]. Side effects such as fatigue and arthralgia were measured with a visual analogue score [VAS]. Skin toxicity was reported with a European Organization for Research and Treatment of Cancer-derived score. In all, 252 IBD patients on maintenance anti-TNF therapy were screened, of whom 95 [73 with Crohn's disease, 22 with ulcerative colitis; 72 on IFX, 23 on ADA] were in clinical and biochemical remission and were included. Median TLs were 5.5 µg/ml and 6.6 µg/ml for IFX and ADA, respectively. Patients with anti-TNF TLs above median had lower IBDQ scores than patients with lower TLs [IBDQ 176 vs 187, p = 0.02], particularly regarding systemic symptoms and emotional status. A trend towards lower SF-36 and higher fatigue scores was observed in the higher anti-TNF TL group. Skin and arthralgia scores were not significantly different between the groups. IBD patients with higher anti-TNF serum concentrations had significantly lower disease-specific QoL. Fatigue, arthralgia, and skin lesions do not occur more often in these patients. These data are reassuring that high serum concentrations of anti-TNF antibodies are not toxic. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email

  2. Filling of High-Concentration Monoclonal Antibody Formulations: Investigating Underlying Mechanisms That Affect Precision of Low-Volume Fill by Peristaltic Pump.

    PubMed

    Shieu, Wendy; Lamar, Dax; Stauch, Oliver B; Maa, Yuh-Fun

    2016-01-01

    Filling of high-concentration/viscosity monoclonal antibody formulations into vials or syringes by peristaltic pumps is an industrial standard. Control of the peristaltic pump on fill weight/volume accuracy/precision over time, however, has not been fully disclosed in the literature. This study systematically evaluated the impact of a broad range of system/pump parameters, from tubing setup to pump parameter settings to the filling nozzle, on filling precision using a bench-top system with fill weight readings from a high-precision balance. A low fill volume of 0.3 mL was targeted to fill liquids of various viscosities (including a high-concentration monoclonal antibody formulation). Fill weight precision was reported via percent of fill weight data points (at least 100 consecutive points) falling within 3% of the target fill weight (e.g., within 0.009 g for a 0.3 g target fill weight). Experimental results suggested that the 3% precision target is challenging for filling high-viscosity liquids due to run-to-run and day-to-day variability. More importantly, none of the system/pump parameters seemed to directly correlate with fill weight precision. Photograph analysis revealed liquid suck-back height variations during fill, which correlated well with fill weight variability. Suck-back height variation was attributed to two possible root causes: (1) inconsistent liquid stream separation point at the end of fill and (2) pressure-induced variations upon suck-back. Liquid stream break-up was influenced by liquid properties as well as liquid/nozzle interactions, and pressure variations might be associated with tubing and overall mechanism of the peristaltic pump. A custom nozzle tip design featuring a hydrophobic tip and a pressure-resistance barrier enabled consistent suck-back heights for each fill and approximately 90% of fill weight data within 3% precision for a high-concentration monoclonal antibody formulation. Vial and syringe filling by peristaltic pump is

  3. Concentrations of Immunoglobulin G Antibodies Against Pertussis Toxin Does Not Decrease Over a Long Period of Time in Japan.

    PubMed

    Sakakibara, Yumi; Ohtani, Yoshio; Jinta, Torahiko; Fujie, Toshihide; Miyazaki, Yasunari; Inase, Naohiko; Saito, Ryoichi; Akaza, Miho; Sasano, Tetsuo; Sumi, Yuki

    Objective Adult patients with pertussis rarely show typical symptoms, such as paroxysmal coughing, inspiratory "whoop", or post-tussive vomiting. While a culture is regarded as the gold standard for diagnosis, the sensitivity is very low. Therefore, the diagnosis of pertussis in adults in clinical practice is mostly based on single-sample serology using an enzyme-linked immunosorbent assay (ELISA) with the pertussis toxin antigen. Various cut-off values for the anti-pertussis toxin IgG (PT-IgG) have been proposed. It has been reported that concentrations of PT-IgG fall below the defined cut-off about 4.5 months after infection on average, and within 1 year in most patients. We investigated the distribution and time course of the PT-IgG levels. Methods The data were collected from the medical records. Patients The study retrospectively identified subjects who had visited Ikebukuro Otani Clinic, which is a specialized clinic for patients with cough. We retrospectively reviewed 406 patients with PT-IgG measurements to investigate the age distribution of PT-IgG levels. The changes in PT-IgG levels over time were assessed in the 205 patients who had more than one PT-IgG measurement. Results PT-IgG levels were ≥100 EU/mL in more than 15% of subjects. The PT-IgG levels of a few subjects had diminished over a long period of time. Conclusion A PT-IgG level greater than the defined cut-off value simply indicates past infection or immunization in most subjects. As such, a single measurement of PT-IgG using the cut-off values might lead to overdiagnosis of pertussis. Further data collection and analysis are required.

  4. Concentrations of Immunoglobulin G Antibodies Against Pertussis Toxin Does Not Decrease Over a Long Period of Time in Japan

    PubMed Central

    Sakakibara, Yumi; Ohtani, Yoshio; Jinta, Torahiko; Fujie, Toshihide; Miyazaki, Yasunari; Inase, Naohiko; Saito, Ryoichi; Akaza, Miho; Sasano, Tetsuo; Sumi, Yuki

    2016-01-01

    Objective Adult patients with pertussis rarely show typical symptoms, such as paroxysmal coughing, inspiratory “whoop”, or post-tussive vomiting. While a culture is regarded as the gold standard for diagnosis, the sensitivity is very low. Therefore, the diagnosis of pertussis in adults in clinical practice is mostly based on single-sample serology using an enzyme-linked immunosorbent assay (ELISA) with the pertussis toxin antigen. Various cut-off values for the anti-pertussis toxin IgG (PT-IgG) have been proposed. It has been reported that concentrations of PT-IgG fall below the defined cut-off about 4.5 months after infection on average, and within 1 year in most patients. We investigated the distribution and time course of the PT-IgG levels. Methods The data were collected from the medical records. Patients The study retrospectively identified subjects who had visited Ikebukuro Otani Clinic, which is a specialized clinic for patients with cough. We retrospectively reviewed 406 patients with PT-IgG measurements to investigate the age distribution of PT-IgG levels. The changes in PT-IgG levels over time were assessed in the 205 patients who had more than one PT-IgG measurement. Results PT-IgG levels were ≥100 EU/mL in more than 15% of subjects. The PT-IgG levels of a few subjects had diminished over a long period of time. Conclusion A PT-IgG level greater than the defined cut-off value simply indicates past infection or immunization in most subjects. As such, a single measurement of PT-IgG using the cut-off values might lead to overdiagnosis of pertussis. Further data collection and analysis are required. PMID:27853066

  5. Concentration of anti-pneumococcal capsular polysaccharide IgM, IgG and IgA specific antibodies in adult blood donors.

    PubMed

    Parker, Antony R; Allen, Syreeta; Harding, Stephen

    2016-08-01

    Anti-pneumococcal capsular polysaccharide (PCP) IgM, IgG and IgA ELISAs have been developed to aid assessment of the adaptive immune system. The relationship between the concentrations of PCP IgM, IgG, and IgA was investigated. The concentrations of PCP IgM, IgG, and IgA were measured in sera obtained from 231 adult blood donors. Concentrations of each isotype were not normally distributed. The median concentration for PCP IgM was 54 U/mL (range 37-75 U/mL), IgG 40 mg/L (range 26-79 mg/L) and IgA 21 U/mL (range 13-44 U/mL). The median PCP IgM titres decreased with age and were significantly lower in patients aged 81-90 years compared to those aged 18-80 years. By contrast, there was a significantly higher median serum PCP IgG titre in the 61-90 years group compared to those aged 18-60 years and a significantly higher median serum PCP IgA titre in the 51-90 years group compared to those aged 18-50 years. The correlation between PCP IgG and IgA was more significant than between IgM and IgA and between IgM and IgG. Correlation of PCP IgA and IgM concentrations identified four phenotypes: high PCP IgM and IgA; high PCP IgM only; high PCP IgA only; and low PCP IgM and IgA. A significant number of individuals with a PCP IgG concentration >50 mg/L had low PCP IgA and IgM concentrations. The additional measurement of PCP IgA and PCP IgM, alongside PCP IgG, in individuals investigated for a compromised immune system may provide a more detailed antibody profile.

  6. Cost-effectiveness of combined serum anti-Helicobacter pylori IgG antibody and serum pepsinogen concentrations for screening for gastric cancer risk in Japan.

    PubMed

    Saito, Shota; Azumi, Motoi; Muneoka, Yusuke; Nishino, Katsuhiko; Ishikawa, Takashi; Sato, Yuichi; Terai, Shuji; Akazawa, Kouhei

    2017-05-26

    A combination of assays for the presence of serum anti-Helicobacter pylori IgG antibody (HPA) and serum pepsinogen (PG) concentrations can be used to screen for gastric cancer risk. In Japan, this "ABC method" is considered an effective means of stratifying gastric cancer risk. This study aimed to ascertain its cost-effectiveness for assessing gastric cancer risk. A Markov model was constructed to compare the cost-effectiveness of two strategies for gastric cancer-risk screening over a 30-year period: the ABC method, which uses a combination of assessing the presence of HPA and measuring serum PG concentrations and scheduling endoscopies accordingly, and annual endoscopic screening. Clinical and epidemiological data on variables in the model were obtained from published reports. Analyses were made from the perspective of the Japanese health care payer. According to base-case analysis, the ABC method cost less than annual endoscopic screening (64,489 vs. 64,074 USD) and saved more lives (18.16 vs. 18.30 quality-adjusted life years). One-way analyses confirmed the robustness of the cost-effectiveness results. The probability that the ABC method is cost-effective in Japanese individuals aged 50 years was 0.997. A combination of HPA and serum PG assays, plus scheduling endoscopy accordingly, is a cost-effective method of screening for gastric cancer risk in Japan.

  7. Viscosity-Lowering Effect of Amino Acids and Salts on Highly Concentrated Solutions of Two IgG1 Monoclonal Antibodies.

    PubMed

    Wang, Shujing; Zhang, Ning; Hu, Tao; Dai, Weiguo; Feng, Xiuying; Zhang, Xinyi; Qian, Feng

    2015-12-07

    Monoclonal antibodies display complicated solution properties in highly concentrated (>100 mg/mL) formulations, such as high viscosity, high aggregation propensity, and low stability, among others, originating from protein-protein interactions within the colloidal protein solution. These properties severely hinder the successful development of high-concentration mAb solution for subcutaneous injection. We hereby investigated the effects of several small-molecule excipients with diverse biophysical-chemical properties on the viscosity, aggregation propensity, and stability on two model IgG1 (JM1 and JM2) mAb formulations. These excipients include nine amino acids or their salt forms (Ala, Pro, Val, Gly, Ser, HisHCl, LysHCl, ArgHCl, and NaGlu), four representative salts (NaCl, NaAc, Na2SO4, and NH4Cl), and two chaotropic reagents (urea and GdnHCl). With only salts or amino acids in their salt-forms, significant decrease in viscosity was observed for JM1 (by up to 30-40%) and JM2 (by up to 50-80%) formulations, suggesting charge-charge interaction between the mAbs dictates the high viscosity of these mAbs formulations. Most of these viscosity-lowering excipients did not induce substantial protein aggregation or changes in the secondary structure of the mAbs, as evidenced by HPLC-SEC, DSC, and FT-IR analysis, even in the absence of common protein stabilizers such as sugars and surfactants. Therefore, amino acids in their salt-forms and several common salts, such as ArgHCl, HisHCl, LysHCl, NaCl, Na2SO4, and NaAc, could potentially serve as viscosity-lowering excipients during high-concentration mAb formulation development.

  8. Conference Planning.

    ERIC Educational Resources Information Center

    Burke, W. Warner, Ed.; Beckhard, Richard, Ed.

    This book, written to instruct in the use of a conference as a medium of social intercourse, is divided into four sections. Section I, which contains five articles, deals with factors to be considered in planning a conference. Specific techniques one can employ to improve a conference and several different techniques for evaluating the…

  9. Prediction of Pneumococcal Conjugate Vaccine Effectiveness against Invasive Pneumococcal Disease Using Opsonophagocytic Activity and Antibody Concentrations Determined by Enzyme-Linked Immunosorbent Assay with 22F Adsorption ▿

    PubMed Central

    Schuerman, L.; Wysocki, J.; Tejedor, J. C.; Knuf, M.; Kim, K.-H.; Poolman, J.

    2011-01-01

    We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (≥0.2 μg/ml) and OPA assay (titer, ≥8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of ≥0.2 μg/ml IgG and an OPA titer of ≥8 corresponded well with overall effectiveness against IPD. In addition, the OPA assay seemed to better predict serotype-specific effectiveness than enzyme-linked immunoassay. Finally, when applied to post-dose-2 immune responses, both thresholds also corresponded well with the overall IPD effectiveness following a 2-dose 7vCRM primary vaccination. These results support the importance of the OPA assay in evaluating immune responses to pneumococcal conjugate vaccines. PMID:21994351

  10. Serum pharmacokinetics and cerebrospinal fluid concentration analysis of the new IgG4 monoclonal antibody GNbAC1 to treat multiple sclerosis: A Phase 1 study

    PubMed Central

    Curtin, François; Vidal, Virginie; Bernard, Corinne; Kromminga, Arno; Lang, Alois B.; Porchet, Hervé

    2016-01-01

    ABSTRACT GNbAC1 is a humanized IgG4 monoclonal antibody antagonist of Mulitple Sclerosis Retrovirus Envelope (MSRV-Env), a protein that could play a critical role in multiple sclerosis. This randomized placebo-controlled dose-escalation study evaluated the safety and pharmacokinetics of GNbAC1 in 21 healthy volunteers after single intravenous infusion at doses of 6, 18 and 36 mg/kg. Lumbar punctures were performed at days 2, 15 or 29 to measure GNbAC1 concentrations in cerebrospinal fluid (CSF). GNbAC1 was well tolerated. Serum data show a dose-linear pharmacokinetics. A mean CSF/serum ratio of 0.12% was observed at Day 2, increasing to 0.39% at Day 15 and 0.42% at Day 29. Linear regression analysis shows a relationship between GNbAC1 CSF/serum ratio and albumin CSF/serum ratio and a relationship at the limit of statistical significance with the timing of CSF sampling. PMID:27030142

  11. Technical Decision-Making with Higher Order Structure Data: Detecting Reversible Concentration-Dependent Self-Association in a Monoclonal Antibody and a Preliminary Investigation to Eliminate It.

    PubMed

    Wei, Julie Y; Bou-Assaf, George M; Houde, Damian; Weiskopf, Andrew

    2015-11-01

    Protein self-association or aggregation is a property of significant concern for biopharmaceutical products due to the potential ability of aggregates to cause adverse toxicological and immunological effects. Thus, during the development of a protein biopharmaceutical, it is important to detect and quantify the level and nature of aggregate species as early as possible in order to make well-informed decisions and to mitigate and control potential risks. Although a deeper understanding of the mechanism of aggregation (i.e., protein-protein interactions) is desirable, such detailed assessment is not always necessary from a biopharmaceutical process development point of view. In fact, the scope of characterization efforts is often focused on achieving a well-controlled process, which generates a product that reliably meets established acceptance criteria for safety and efficacy. In this brief note, we evaluated the utility of size-exclusion chromatography, dynamic light scattering, and analytical ultracentrifugation in their simplest forms, to effectively reveal and confirm the presence of concentration-dependent reversible self-association (RSA) in a monoclonal antibody in the early stages of formulation development. Using these techniques, we also initiated preliminary work aimed at reducing the occurrence of this RSA behavior by varying the pH of the formulation buffer. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. Antimitochondrial antibody

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003529.htm Antimitochondrial antibody To use the sharing features on this page, please enable JavaScript. Antimitochondrial antibodies (AMA) are substances ( antibodies ) that form against mitochondria. ...

  13. Inhibin immunoneutralization by antibodies raised against synthetic peptide sequences of inhibin alpha subunit: effects on gonadotrophin concentrations and ovulation rate in sheep.

    PubMed

    Wrathall, J H; McLeod, B J; Glencross, R G; Beard, A J; Knight, P G

    1990-01-01

    Two experiments were conducted to explore the effectiveness of synthetic peptide-based vaccines for active and passive autoimmunization of sheep against inhibin. In the first experiment, adult Romney ewes (n = 20) were actively immunized against a synthetically produced peptide that corresponded to the N-terminus of the alpha-subunit of bovine inhibin (bI alpha(1-29)-Tyr30). This peptide was conjugated to tuberculin purified protein derivative (PPD) to increase its antigenic properties. Control groups comprised non-immunized (n = 10) and PPD-immunized (n = 10) ewes. Primary immunization (400 micrograms conjugate/ewe) was followed by two booster immunizations (200 micrograms conjugate/ewe), given 5 and 8 weeks later. Following synchronization of oestrus using progestagen sponges, ovulation rates were assessed by laparoscopy. Weekly blood samples were taken throughout the experiment. All inhibin-immunized ewes produced antibodies which bound 125I-labelled bovine inhibin (Mr 32,000), and ovulation rate in inhibin-immunized ewes (2.15 +/- 0.22; mean +/- S.E.M.) was significantly (P less than 0.01) greater than in both non-immunized (0.90 +/- 0.23) and PPD-immunized (1.20 +/- 0.13) control groups. Immunization against the peptide, but not against PPD alone, resulted in a modest rise in plasma FSH, with mean levels after the second boost being significantly (P less than 0.025) higher (22%) than those before immunization. Moreover, when blood samples were taken (2-h intervals) from randomly selected groups of control (n = 7) and inhibin-immunized (n = 7) ewes for an 84-h period following withdrawal of progestagen sponges, the mean plasma concentration of FSH during the 48 h immediately before the preovulatory LH surge was 37% greater (P less than 0.025) in immunized than in control animals. However, more frequent blood sampling (every 15 min for 12 h) during follicular and mid-luteal phases of the oestrous cycle revealed no significant differences between treatment groups

  14. Effect of α7n-Acetylcholine Receptor Activation and Antibodies to TNF-α on Mortality of Mice and Concentration of Proinflammatory Cytokines During Early Stage of Sepsis.

    PubMed

    Zabrodskii, P F; Gromov, M S; Maslyakov, V V

    2015-10-01

    Experiments on random-bred albino mice showed that activation α7n-acetylcholine receptors with anabasine (0.5 LD50) and the use of antibodies to TNF-α (1 mg/kg) 2 h before sepsis modeling significantly reduces mortality of mice from experimental sepsis (intraperitoneal injection of E. coli) due to a decrease in the blood concentration of proinflammatory cytokines TNF-α, IL-1β, and IL-6. After combined administration of anti-TNF-α antibodies and anabasine, an additive effect was observed.

  15. Antibody engineering and therapeutics, The Annual Meeting of the Antibody Society: December 8-12, 2013, Huntington Beach, CA.

    PubMed

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul W H I; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates.

  16. Cerebral distribution of immunoconjugate after treatment for neoplastic meningitis using an intrathecal radiolabeled monoclonal antibody

    SciTech Connect

    Benjamin, J.C.; Moss, T.; Moseley, R.P.; Maxwell, R.; Coakham, H.B. )

    1989-08-01

    A detailed autopsy and autoradiographic study was performed after the death of a patient undergoing intrathecal, antibody-guided irradiation for carcinomatous meningitis. The results demonstrated tumor cells infiltrating the surface meninges and a severe astrocytic reaction associated with oedema in the periventricular and brain stem subpial white matter. This was not seen in cortical or other gray matter structures. Autoradiographic examination correlated well, demonstrating isotope within the oedematous areas of the white matter in addition to the expected concentration in the leptomeningeal layers. These findings are discussed in the context of antibody binding to tumor tissue and the possible benefits conferred in the treatment of infiltrating tumor cells.

  17. Antibody Gene Transfer for HIV Immunoprophylaxis

    PubMed Central

    Balazs, Alejandro B.; West, Anthony P.

    2015-01-01

    Antibody gene transfer, which involves the delivery of genes that encode potent, broadly neutralizing anti-HIV antibodies, is a promising new strategy to prevent HIV infection. A satellite symposium at the AIDS Vaccine 2012 conference brought together many of the groups working in this field. PMID:23238748

  18. Antibody gene transfer for HIV immunoprophylaxis.

    PubMed

    Balazs, Alejandro B; West, Anthony P

    2013-01-01

    Antibody gene transfer, which involves the delivery of genes that encode potent, broadly neutralizing antibodies to human immunodeficiency virus (HIV), is a promising new strategy for preventing HIV infection. A satellite symposium at the AIDS Vaccine 2012 conference brought together many of the groups working in this field.

  19. Conference Resolution

    NASA Astrophysics Data System (ADS)

    2009-04-01

    Since the first IUPAP International Conference on Women in Physics (Paris, March 2002) and the Second Conference (Rio de Janeiro, May 2005), progress has continued in most countries and world regions to attract girls to physics and advance women into leadership roles, and many working groups have formed. The Third Conference (Seoul, October 2008), with 283 attendees from 57 countries, was dedicated to celebrating the physics achievements of women throughout the world, networking toward new international collaborations, building each participant's capacity for career success, and aiding the formation of active regional working groups to advance women in physics. Despite the progress, women remain a small minority of the physics community in most countries.

  20. Summary of 1990 Code Conference

    SciTech Connect

    Cooper, R.K.; Chan, Kwok-Chi D.

    1990-01-01

    The Conference on Codes and the Linear Accelerator Community was held in Los Alamos in January 1990, and had approximately 100 participants. This conference was the second in a series which has as its goal the exchange of information about codes and code practices among those writing and actually using these codes for the design and analysis of linear accelerators and their components. The first conference was held in San Diego in January 1988, and concentrated on beam dynamics codes and Maxwell solvers. This most recent conference concentrated on 3-D codes and techniques to handle the large amounts of data required for three-dimensional problems. In addition to descriptions of codes, their algorithms and implementations, there were a number of paper describing the use of many of the codes. Proceedings of both these conferences are available. 3 refs., 2 tabs.

  1. Monoclonal Antibodies.

    ERIC Educational Resources Information Center

    Killington, R. A.; Powell, K. L.

    1984-01-01

    Monoclonal antibodies have provided an exciting addition to the "armory" of the molecular biologist and immunologist. This article discusses briefly the concept of, techniques available for, production of, and possible uses of monoclonal antibodies. (Author)

  2. Monoclonal Antibodies.

    ERIC Educational Resources Information Center

    Killington, R. A.; Powell, K. L.

    1984-01-01

    Monoclonal antibodies have provided an exciting addition to the "armory" of the molecular biologist and immunologist. This article discusses briefly the concept of, techniques available for, production of, and possible uses of monoclonal antibodies. (Author)

  3. Biomedical Conferences

    NASA Technical Reports Server (NTRS)

    1976-01-01

    As a result of Biomedical Conferences, Vivo Metric Systems Co. has produced cardiac electrodes based on NASA technology. Frequently in science, one highly specialized discipline is unaware of relevant advances made in other areas. In an attempt to familiarize researchers in a variety of disciplines with medical problems and needs, NASA has sponsored conferences that bring together university scientists, practicing physicians and manufacturers of medical instruments.

  4. Antithyroid microsomal antibody

    MedlinePlus

    Thyroid antimicrosomal antibody; Antimicrosomal antibody; Microsomal antibody; Thyroid peroxidase antibody; TPOAb ... Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also been linked with an increased risk ...

  5. Differences in modifications of cytoplasmic free Ca2+ concentration and 86Rb+ influx in human neoplastic B cells by antibodies to mu- relative to delta-Ig heavy chains.

    PubMed Central

    Heikkilä, R; Ruud, E; Funderud, S; Godal, T

    1985-01-01

    Cytoplasmic free Ca2+ concentration and influx of 86Rb+ (K+ analogue) were determined during the first minutes after stimulation of neoplastic human B cells and B cell lines by antibodies to surface Ig. The Ca2+ concentration increased in the great majority of samples (41 of 48). All of four B cell lines also responded, providing formal evidence that accessory cells are not required for this early, surface Ig-mediated event. Antibodies to delta as well as mu, heavy chains (anti-delta and anti-mu) could induce both Ca2+ and 86Rb+ responses. 86Rb+ responders were found within the group of Ca2+ responders, but no quantitative relation was observed between the two responses. In cells expressing both sIgM and sIgD, antibodies to delta heavy chains were more potent than those to mu heavy chains in inducing Ca2+ responses, whereas the opposite pattern was seen with regard to 86Rb+ responses. These results demonstrate that sIgM and sIgD can deliver different biochemical signals to the cell. PMID:3921300

  6. Accuracy of a point-of-care ELISA test kit for predicting the presence of protective canine parvovirus and canine distemper virus antibody concentrations in dogs.

    PubMed

    Litster, A L; Pressler, B; Volpe, A; Dubovi, E

    2012-08-01

    Canine parvovirus (CPV) and canine distemper virus (CDV) are highly infectious and often fatal diseases with worldwide distributions, and are important population management considerations in animal shelters. A point-of-care ELISA test kit is available to detect serum antibodies to CPV and CDV, and presumptively to predict protective status. The aim of this study was to determine the diagnostic accuracy of the test compared to CPV hemagglutination inhibition titers and CDV serum neutralization titers determined by a reference laboratory, using sera collected from dogs housed at animal shelters. The ELISA test was used under both field and laboratory conditions and duplicate specimens were processed using an extra wash step. The test kit yielded accurate results (CPV: sensitivity 92.3%, specificity 93.5%; CDV: sensitivity 75.7%, specificity 91.8%) under field conditions. CDV sensitivity was improved by performing the test under laboratory conditions and using an optical density (OD) meter (laboratory performed 94.0%; OD 88.1%). Point-of-care ELISA testing for serum CPV and CDV antibody titers was demonstrated to be a useful tool for determining antibody status when making decisions regarding the need for CPV and/or CDV vaccination and also in animal shelters for population management.

  7. Absolute quantification of the total and antidrug antibody-bound concentrations of recombinant human α-glucosidase in human plasma using protein G extraction and LC-MS/MS.

    PubMed

    Bronsema, Kees J; Bischoff, Rainer; Pijnappel, W W M Pim; van der Ploeg, Ans T; van de Merbel, Nico C

    2015-04-21

    The administration of protein-based pharmaceuticals can cause the in vivo formation of antidrug antibodies (ADAs), which may reduce the efficacy of the therapy by binding to the protein drug. An accurate determination of the total and ADA-bound concentrations of the drug gives information on the extent of this immune response and its consequences and may help develop improved therapeutic regimens. We present an absolute quantitative method to differentiate between total, free, and ADA-bound drug for recombinant human alpha acid glucosidase (rhGAA) in plasma from patients suffering from Pompe's disease. LC-MS/MS quantification of a signature peptide after trypsin digestion of plasma samples before and after an extraction of the total IgG content of plasma with protein G coated beads was used to determine the total and the ADA-bound fractions of rhGAA in samples from Pompe patients after enzyme infusion. The methods for total and ADA-bound rhGAA allow quantitation of the drug in the range of 0.5 to 500 μg/mL using 20 μL of plasma and met the regular bioanalytical validation requirements, both in the absence and presence of high levels of anti-rhGAA antibodies. This demonstrates that the ADA-bound rhGAA fraction can be accurately and precisely determined and is not influenced by sample dilution, repeated freezing and thawing, or extended benchtop or frozen storage. In samples from a patient with a reduced response to therapy due to ADAs, high ADA-bound concentrations of rhGAA were found, while in the samples from a patient lacking ADAs, no significant ADA-bound concentrations were found. Since protein G captures the complete IgG content of plasma, including all antidrug antibodies, the described extraction approach is universally applicable for the quantification of ADA-bound concentrations of all non-IgG-based biopharmaceuticals.

  8. Conference reports

    NASA Astrophysics Data System (ADS)

    Dongpei, Chen; Yulong, Ma

    1994-12-01

    The Ultrasonic Electronics Branch Society of the China Acoustics Society, and the Electronics Countermeasure Branch Society of the China Electronics Society held and All-China Applications Conference of Ultrasonic Electronics Devices in Electronic Countermeasures, Radar and Military Communication Technology. A total of 66 papers was received by the conference with contents relating to surface acoustic wave devices, high-frequency acoustic wave devices, acousto-optical devices, applications of devices in radar, applications of devices in electronic countermeasures, and applications of devices in military communication systems.

  9. Human Monoclonal Antibodies Generated Following Vaccination with AVA Provide Neutralization by Blocking Furin Cleavage but not by Preventing Oligomerization

    PubMed Central

    Smith, Kenneth; Crowe, Sherry R.; Garman, Lori; Guthridge, Carla; Muther, Jennifer J.; McKee, Emily; Farris, A. Darise; Guthridge, Joel M.; Wilson, Patrick C.; James, Judith A.

    2012-01-01

    In order to identify the combination of antibody-mediated mechanisms of neutralization that result from vaccination with anthrax vaccine adsorbed (AVA), we isolated antibody secreting cells from a single donor seven days after booster vaccination with AVA and generated nine fully human monoclonal antibodies (hmAb) with high specificity for protective antigen (PA). Two of the antibodies were able to neutralize lethal toxin in vitro at low concentrations (IC50: p6C01, 0.12 µg/ml and p6F01, 0.45 µg/ml). Passive transfer of either of these hmAbs to A/J mice prior to challenge with lethal toxin conferred 80–90% protection. We demonstrate that hmAb p6C01 is neutralizing by preventing furin cleavage of PA in a dose-dependent manner, but the mechanism of p6F01 is unclear. Three additional antibodies were found to bind to domain 3 of PA and prevent oligomerization, although they did not confer significant protection in vivo and showed a significant prozone-like effect in vitro. These fully human antibodies provide insight into the neutralizing response to AVA for future subunit vaccine and passive immunotherapeutic cocktail design. PMID:22425791

  10. Conference Summary

    ERIC Educational Resources Information Center

    Doherty, Cait

    2009-01-01

    This article summarizes an original conference, organised by the Child Care Research Forum (http://www.qub.ac.uk/sites/ccrf/), which brought together experts from all over Northern Ireland to showcase some of the wealth of research with children and young people that is going on in the country today. Developed around the six high-level outcomes of…

  11. The conference

    Treesearch

    Gordon M. Heisler; Lee P. Herrington

    1977-01-01

    This is a report on the Conference on Metropolitan Physical Environment, held in August 1975 at Syracuse, N.Y., where some 160 scientists and planners met to discuss the use of vegetation, space, and structures to improve the amenities for people who live in metropolitan areas.

  12. Conference Space

    ERIC Educational Resources Information Center

    Tillett, Wade

    2016-01-01

    The following is an exploration of the spatial configurations (and their implications) within a typical panel session at an academic conference. The presenter initially takes up different roles and hyperbolically describes some possible messages that the spatial arrangement sends. Eventually, the presenter engages the audience members in atypical…

  13. Conference Space

    ERIC Educational Resources Information Center

    Tillett, Wade

    2016-01-01

    The following is an exploration of the spatial configurations (and their implications) within a typical panel session at an academic conference. The presenter initially takes up different roles and hyperbolically describes some possible messages that the spatial arrangement sends. Eventually, the presenter engages the audience members in atypical…

  14. Antibody Engineering & Therapeutics, the annual meeting of The Antibody Society December 7-10, 2015, San Diego, CA, USA.

    PubMed

    Pauthner, Matthias; Yeung, Jenny; Ullman, Chris; Bakker, Joost; Wurch, Thierry; Reichert, Janice M; Lund-Johansen, Fridtjof; Bradbury, Andrew R M; Carter, Paul J; Melis, Joost P M

    2016-01-01

    The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6-10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on "Antibodies to watch" in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries.

  15. High Concentrations of Angiopoietin-Like Protein 4 Detected in Serum from Patients with Rheumatoid Arthritis Can Be Explained by Non-Specific Antibody Reactivity

    PubMed Central

    Makoveichuk, Elena; Ruge, Toralph; Nilsson, Solveig; Södergren, Anna

    2017-01-01

    Angiopoietin-like protein 4 (ANGPTL4) is suggested to be a master regulator of plasma triglyceride metabolism. Our aim was to study whether the previously reported high levels of ANGPTL4 detected in serum from patients with rheumatoid arthritis (RA) by ELISA was due to any specific molecular form of this protein (oligomers, monomers or fragments). ANGPTL4 levels were first determined in serum from 68 RA patients and 43 age and sex matched control subjects and the mean values differed by a factor of 5.0. Then, ANGPTL4 was analyzed after size exclusion chromatography (SEC) of serum samples. With serum from one of the RA patients with high levels of ANGPTL4, the dominant reactivity was found in fractions corresponding to high-molecular weight proteins. In addition, a minor peak of reactivity eluting late from the column was found both in the patient and in controls. By the use of HeteroBlock®, and by careful selection of antibodies, we documented non-specific reactions for ANGPTL4 in 39% of samples from the RA patients, most likely due to cross-reactivity of the antibodies with rheumatoid factor (RF). The corresponding figure for control subjects was 6.3%. After corrections for non-specific reactions, the mean level of ANGPTL4 in serum from RA patients was still significantly higher than in control individuals (mean levels were 101±62 and 67±39 ng/ml respectively, P = 0.02). We re-analyzed samples from our previously published studies on ANGPL4 levels in patients on hemodialysis and patients with diabetes type 2. These samples did not show false positive reactions. The levels of ANGPTL4 were comparable to those detected previously. PMID:28107351

  16. Preclinical Pharmacokinetics Evaluation of Anti-heparin-binding EGF-like Growth Factor (HB-EGF) Monoclonal Antibody Using Cynomolgus Monkeys via (89)Zr-immuno-PET Study and the Determination of Drug Concentrations in Serum and Cerebrospinal Fluid.

    PubMed

    Kasai, Noriyuki; Adachi, Maiko; Yamano, Kazuya

    2016-02-01

    Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family and is an important therapeutic target in some types of human cancers. KHK2866 is a humanized anti-HB-EGF monoclonal antibody IgG that neutralizes HB-EGF activity by inhibiting the binding of HB-EGF to its receptors. The phase I study of KHK2866 was discontinued because of neuropsychiatric toxicity. In this study, the pharmacokinetics of KHK2866 was evaluated by (89)Zr-immuno-PET study and the determination of drug concentrations in serum and cerebrospinal fluid using cynomolgus monkeys was performed in order to predict neurotoxicity in a reverse-translational manner. KHK2866 was radiolabeled with (89)Zr for preclinical evaluations in normal cynomolgus monkeys and its distribution was analyzed. Furthermore, as a separate study, KHK2866 concentrations in serum and cerebrospinal fluid were determined after administration of a single dose. PET studies with monkeys revealed (89)Zr-KHK2866 accumulation in the liver, spleen and joints of multiple parts, but not in brain. In addition, the pharmacokinetic analyses in serum and CSF demonstrated a low penetration of KHK2866 into the brain. These studies indicate the difficulty of prediction for neuropsychiatric toxicity of monoclonal antibodies in human by means of pharmacokinetic evaluations using cynomolgus monkeys.

  17. Seroprevalence of parvovirus B19, cytomegalovirus, hepatitis A virus and hepatitis E virus antibodies in haemophiliacs treated exclusively with clotting-factor concentrates considered safe against human immunodeficiency and hepatitis C viruses.

    PubMed

    Flores, G; Juárez, J C; Montoro, J B; Tusell, J M; Altisent, C; Juste, C; Jardí, R

    1995-04-01

    Clotting-factor concentrates (CFC) are a potential source of transmission of blood-borne viruses. Newer physical and chemical methods (pasteurization, wet-heating, solvent/detergent treating) developed to inactivate viruses are effective against HIV, HBV and HCV. However, it is not clear if these methods protect against other pathogenic viruses such as parvovirus B19, cytomegalovirus (CMV), hepatitis A virus (HAV) and hepatitis E virus (HEV). To evaluate the safety of current CFC we have studied seroprevalence of parovirus B19, CMV, HAV and HEV antibodies in 22 HIV and HCV negative haemophiliacs who were treated exclusively with clotting-factor concentrates considered safe with respect to HIV and HCV transmission, 22 healthy individuals served as controls. Neither HAV nor HEV antibodies were detected in haemophiliacs or controls. Two controls and two haemophiliacs were seropositive for CMV. Five controls (32% prevalence) and 15 haemophiliacs (77%) were positive to parovirus B19. No statistical differences can be established for seropositivity with CMV, HAV and HEV between haemophilic patients and controls. In the case of parvovirus B19 the differences are statistically significant (P= 0.0128). The relative risk of parvovirus B19 is 2.4 in the case of haemophiliacs. CFC considered safe against HIV and HCV are not safe against parvovirus B19, although they seem to be safe against CMV, HAV and HEV.

  18. The making of bispecific antibodies

    PubMed Central

    2017-01-01

    ABSTRACT During the past two decades we have seen a phenomenal evolution of bispecific antibodies for therapeutic applications. The ‘zoo’ of bispecific antibodies is populated by many different species, comprising around 100 different formats, including small molecules composed solely of the antigen-binding sites of two antibodies, molecules with an IgG structure, and large complex molecules composed of different antigen-binding moieties often combined with dimerization modules. The application of sophisticated molecular design and genetic engineering has solved many of the technical problems associated with the formation of bispecific antibodies such as stability, solubility and other parameters that confer drug properties. These parameters may be summarized under the term ‘developability’. In addition, different ‘target product profiles’, i.e., desired features of the bispecific antibody to be generated, mandates the need for access to a diverse panel of formats. These may vary in size, arrangement, valencies, flexibility and geometry of their binding modules, as well as in their distribution and pharmacokinetic properties. There is not ‘one best format’ for generating bispecific antibodies, and no single format is suitable for all, or even most of, the desired applications. Instead, the bispecific formats collectively serve as a valuable source of diversity that can be applied to the development of therapeutics for various indications. Here, a comprehensive overview of the different bispecific antibody formats is provided. PMID:28071970

  19. A single dose of a neuron-binding human monoclonal antibody improves brainstem NAA concentrations, a biomarker for density of spinal cord axons, in a model of progressive multiple sclerosis.

    PubMed

    Wootla, Bharath; Denic, Aleksandar; Watzlawik, Jens O; Warrington, Arthur E; Rodriguez, Moses

    2015-04-29

    Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis (MS). We previously showed that as the disease progresses, a marked decrease in brainstem N-acetyl aspartate (NAA; metabolite associated with neuronal integrity) concentrations, reflecting axon health, is measured. We also demonstrated stimulation of neurite outgrowth by a neuron-binding natural human antibody, IgM12. Treatment with either the serum-derived or recombinant human immunoglobulin M 12 (HIgM12) preserved functional motor activity in the TMEV model. In this study, we examined IgM-mediated changes in brainstem NAA concentrations and central nervous system (CNS) pathology. (1)H-magnetic resonance spectroscopy (MRS) showed that treatment with HIgM12 significantly increased brainstem NAA concentrations compared to controls in TMEV-infected mice. Pathologic analysis demonstrated a significant preservation of axons in the spinal cord of animals treated with HIgM12. This study links drug efficacy of slowing deficits with axon preservation and NAA concentrations in the brainstem in a model of progressive MS. HIgM12-mediated changes of NAA concentrations in the brainstem are a surrogate marker of axon injury/preservation throughout the spinal cord. This study provides proof-of-concept that a neuron-reactive human IgM can be therapeutic and provides a biomarker for clinical trials.

  20. Monoclonal Antibodies against Pectin

    PubMed Central

    Liners, Françoise; Letesson, Jean-Jacques; Didembourg, Christian; Van Cutsem, Pierre

    1989-01-01

    Monoclonal antibodies have been produced that recognize a conformation of homopolygalacturonic acid (pectic acid) induced by an optimum concentration of calcium and sodium of about 1 and 150 millinormal, respectively. The epitope recognized is probably part of the dimers of pectin chains associated according to the `egg box' model. Images Figure 2 PMID:16667195

  1. Monoclonal Antibodies.

    PubMed

    Geskin, Larisa J

    2015-10-01

    Use of monoclonal antibodies (mAbs) has revolutionized cancer therapy. Approaches targeting specific cellular targets on the malignant cells and in tumor microenvironment have been proved to be successful in hematologic malignancies, including cutaneous lymphomas. mAb-based therapy for cutaneous T-cell lymphoma has demonstrated high response rates and a favorable toxicity profile in clinical trials. Several antibodies and antibody-based conjugates are approved for use in clinical practice, and many more are in ongoing and planned clinical trials. In addition, these safe and effective drugs can be used as pillars for sequential therapies in a rational stepwise manner.

  2. Next conference

    NASA Astrophysics Data System (ADS)

    Hexemer, Alexander; Toney, Michael F.

    2010-11-01

    After the successful conference on Synchrotron Radiation in Polymer Science (SRPS) in Rolduc Abbey (the Netherlands), we are now looking forward to the next meeting in this topical series started in 1995 by H G Zachmann, one of the pioneers of the use of synchrotron radiation techniques in polymer science. Earlier meetings were held in Hamburg (1995), Sheffield (2002), Kyoto (2006), and Rolduc (2009). In September of 2012 the Synchrotron Radiation and Polymer Science V conferences will be organized in a joint effort by the SLAC National Accelerator Laboratory and Lawrence Berkeley National Laboratory. Stanford Linear Accelerator Laboratory Stanford Linear Accelerator Laboratory Advanced Light Source at LBL Advanced Light Source at LBL The conference will be organised in the heart of beautiful San Francisco. The program will consist of invited and contributed lectures divided in sessions on the use of synchrotron SAXS/WAXD, imaging and tomography, soft x-rays, x-ray spectroscopy, GISAXS and reflectivity, micro-beams and hyphenated techniques in polymer science. Poster contributions are more than welcome and will be highlighted during the poster sessions. Visits to both SLAC as well as LBL will be organised. San Francisco can easily be reached. It is served by two major international airports San Francisco International Airport and Oakland International Airport. Both are being served by most major airlines with easy connections to Europe and Asia as well as national destinations. Both also boast excellent connections to San Francisco city centre. We are looking forward to seeing you in the vibrant city by the Bay in September 2012. Golden gate bridge Alexander Hexemer Lawrence Berkeley National Laboratory, Advanced Light Source, Berkeley, CA 94720, USA Michael F Toney Stanford Synchrotron Radiation Lightsource, Menlo Pk, CA 94025, USA E-mail: ahexemer@lbl.gov, mftoney@slac.stanford.edu

  3. Conferences revisited

    NASA Astrophysics Data System (ADS)

    Radcliffe, Jonathan

    2008-08-01

    Way back in the mid-1990s, as a young PhD student, I wrote a Lateral Thoughts article about my first experience of an academic conference (Physics World 1994 October p80). It was a peach of a trip - most of the lab decamped to Grenoble for a week of great weather, beautiful scenery and, of course, the physics. A whole new community was there for me to see in action, and the internationality of it all helped us to forget about England's non-appearance in the 1994 World Cup finals.

  4. Clinical utility of newly developed immunoassays for serum concentrations of adalimumab and anti-adalimumab antibodies in patients with Crohn's disease.

    PubMed

    Imaeda, Hirotsugu; Takahashi, Kenichiro; Fujimoto, Takehide; Bamba, Shigeki; Tsujikawa, Tomoyuki; Sasaki, Masaya; Fujiyama, Yoshihide; Andoh, Akira

    2014-01-01

    The appearance of anti-adalimumab antibodies (AAAs) is associated with low serum adalimumab (ADA) trough levels and a decrease of clinical response. The goal of this study was to assess the accuracy and clinical utility of new immunoassays for serum ADA and AAA levels. Serum ADA trough levels and AAA levels were measured using new immunoassays in 40 patients with Crohn's disease (CD) receiving ADA maintenance therapy. Serum ADA trough levels were 12.3 ± 9.6 μg/ml (n = 40) in CD patients, and 14 of 40 patients (35 %) were positive for AAAs. A negative correlation was observed between serum AAA levels and ADA trough levels (y = -6.02x + 18.7, r = -0.54, P < 0.001, n = 40). The ROC (receiver-operator curve) analyses indicated that an ADA trough of 5.9 μg/ml was optimal to maintain negative CRP (C-reactive protein) levels (≤0.3 mg/dl). The ADA trough levels were significantly lower in patients positive for AAAs (5.5 ± 5.4 μg/ml, n = 14) than in patients negative for AAAs (16.0 ± 9.5 μg/ml, n = 26). The CRP and ESR levels were significantly higher in AAA-positive patients than in AAA-negative patients. Serum albumin levels were significantly lower in AAA-positive patients. The positive rate for AAAs in patients who lost a response to infliximab (50 %) was significantly higher than that of anti-TNF-α drug naïve patients (12.5 %). These new assays for serum AAA trough and AAA levels are useful for routine clinical use and may help guide selection of optimal management strategies for IBD patients with a loss of response to ADA.

  5. Back to the future: recombinant polyclonal antibody therapeutics

    PubMed Central

    Wang, Xian-zhe; Coljee, Vincent W.; Maynard, Jennifer A.

    2013-01-01

    Antibody therapeutics are one of the fastest growing classes of pharmaceuticals, with an annual US market over $20 billion, developed to treat a variety of diseases including cancer, auto-immune and infectious diseases. Most are currently administered as a single molecule to treat a single disease, however there is mounting evidence that cocktails of multiple antibodies, each with a unique binding specificity and protective mechanism, may improve clinical efficacy. Here, we review progress in the development of oligoclonal combinations of antibodies to treat disease, focusing on identification of synergistic antibodies. We then discuss the application of modern antibody engineering technologies to produce highly potent antibody preparations, including oligoclonal antibody cocktails and truly recombinant polyclonal antibodies. Specific examples illustrating the synergy conferred by multiple antibodies will be provided for diseases caused by botulinum toxin, cancer and immune thrombocytopenia. The bioprocessing and regulatory options for these preparations will be discussed. PMID:24443710

  6. Localization of a domain in the FimH adhesin of Escherichia coli type 1 fimbriae capable of receptor recognition and use of a domain-specific antibody to confer protection against experimental urinary tract infection.

    PubMed Central

    Thankavel, K; Madison, B; Ikeda, T; Malaviya, R; Shah, A H; Arumugam, P M; Abraham, S N

    1997-01-01

    The FimH subunit of type 1-fimbriated Escherichia coli has been implicated as an important determinant of bacterial adherence and colonization of the urinary tract. Here, we sought to localize the functionally important domain(s) within the FimH molecule and to determine if antibodies against this domain would block adherence of type 1-fimbriated E. coli to the bladder mucosa in situ and in vivo in an established mouse model of cystitis. We generated translational fusion proteins of disparate regions of the FimH molecule with an affinity tag MalE, and tested each of the fusion products in vitro for functional activity. The minimum region responsible for binding mouse bladder epithelial cells and a soluble mannoprotein, horseradish peroxidase, was contained within residues 1-100 of the FimH molecule. We validated and extended these findings by demonstrating that antibodies directed at the putative binding region of FimH or at synthetic peptides corresponding to epitopes within the binding domain could specifically block type 1 fimbriae-mediated bacterial adherence to bladder epithelial cells in situ and yeast cells in vitro. Next, we compared the ability of mice passively immunized intraperitoneally with antisera raised against residues 1-25 and 253-264 of FimH or 1-13 of FimA to resist bladder colonization in vivo after intravesicular challenge with type 1-fimbriated E. coli. Only the antibody directed at the putative binding region of FimH (anti- s-FimH1-25) significantly reduced E. coli bladder infections in the experimental mouse model of urinary tract infections. Similar results were obtained when the mice were actively immunized with synthetic peptides corresponding to residues 1-25 and 253-264 of FimH or 1-13 of FimA. The mechanism of protection was attributed, at least in part, to inhibition of bacterial adherence to the bladder surface by s-FimH1-25-specific antibody molecules that had filtered through the kidneys into the urine. The level of Fim

  7. Antibody therapies in CNS diseases.

    PubMed

    Freskgård, Per-Ola; Urich, Eduard

    2017-07-01

    Therapeutic antibodies have essentially been banned from the central nervous system, and are so far limited to use mainly in multiple sclerosis. This is primarily due to the fact that antibody penetration across the blood-brain barrier is very limited, with about only 0.1% of circulating antibodies estimated to reach the brain at steady-state concentration. Nonetheless, advances are being made with conventional antibodies, showing that minimal exposure can act centrally to mediate therapeutic effects. Immunotherapy in Alzheimer's disease is a noteworthy example where antibodies against amyloid-β are able to reduce brain plaque pathology in preclinical models and humans. However, the advances in using antibodies directed at brain targets have also demonstrated impediments of low brain exposure in achieving clinical benefits, spurring increased attention in technologies designed to improve brain exposure of antibodies. Here we review antibodies in clinical trials for central nervous system disorders. Moreover, we describe some of the efforts to improve the therapeutic efficacy of antibodies by enhancing delivery across the blood-brain barrier. This article is part of the Special Issue entitled "Beyond small molecules for neurological disorders". Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. [Determination of plasma concentrations of antioxidants, antibodies against oxidized LDL, and homocysteine in a population sample from Liège].

    PubMed

    Pincemail, J; Siquet, J; Chapelle, J P; Cheramy-Bien, J P; Paulissen, G; Chantillon, A M; Christiaens, G; Gielen, J; Limet, R; Defraigne, J O

    2000-01-01

    A large number of epidemiological and clinical studies suggest that oxidative stress plays an important role in the development of cardiovascular diseases. In this way, following reference values in plasmatic antioxidants have been determined in a group of 123 blood donors (94 males, 29 females; age: 21-64 years) living in the surroundings of Liege, Belgium: vitamin A (1.5-3.62 mmol/l), vitamin C (3.68-75.21 mmol/l), vitamin E (16.98-46.46 mmol/l), ratio vitamin E/cholesterol (3.92-8.32 mmol/mmol), selenium (0.66-1.26 mmol/l), sulphydryl proteins (216-556 mmol/l), uric acid (174-477 mmol/l), superoxide dismutase (542-852 IU/g hemoglobine), glutathion peroxidase (39.55-91.83 IU/g hemoglobine). Only a few number of subjects were found with values corresponding to high risk of deficiency in antioxidants although low values in vitamin C (< 11.35 mmol/l) and in selenium (< 0.75 mmol/l) were respectively observed in 5.69 and 10.5% of our subjects. Autoantibodies against oxidized LDL, as marker of oxidative stress, and homocysteine, as a risk factor of atherosclerosis involved in the development of oxidative stress, have also been investigated. Approximatively 40% of the population presented values higher than the superior limit mean value (20.3% > 650 IU/l in autoantibodies and 19.5% > 15.2 mmol/l in homocysteine) that are, however, not correlated with age or low levels in antioxidants. The effect of smoking (25% of the population) contributed to significantly decrease vitamin C, selenium and glutathion peroxidase concentrations by 31.9 and 13% when compared to nonsmokers. Intake of 1 to 4 fruits per day resulted in a significant increase of 56.9% in vitamin C when compared to nonconsumers (26.8% of the population). In contrast, homocysteine concentrations were significantly decreased by 21.4% in fruits consumers. Thank to the development of methods allowing the routine dosage of all these parameters, general practitioners can now easily establish the oxidative stress

  9. Antibodies against Haemophilus influenzae type b in The Gambia: investigating the extent of protection across age groups.

    PubMed

    Idoko, O T; Roberts, E; Cox, M; Jafali, J; Njie-Jobe, J; Mackenzie, G; Ota, M O; Kampmann, B

    2014-08-06

    Following a landmark clinical trial, the vaccine against Haemophilus influenzae type b (Hib) was introduced in The Gambia in 1997. Whilst the immunogenicity of this vaccine is well established subsequent to the doses administered under the EPI schedule, little data exists assessing longevity of protection, using serology. Such data are needed however to predict the susceptibility to Hib at the population level. To determine antibody persistence in 5-6 year old fully vaccinated Gambian children compared with older children, adolescents and young adults, 427 serum samples from healthy 5-37 year old participants were tested for Hib antibodies using VaccZyme Human Anti-Hib ELISA kits. 86% of the children who had received 3 doses of Hib vaccine in infancy had Hib antibody concentrations ≥0.15 mg/l at the age of 5-6 years. This proportion was 76% for adolescents who had also largely been vaccinated and 90% for adults who had never received Hib vaccine. Although most participants had anti-Hib antibody above concentrations putatively defined as protective, significantly fewer had concentrations thought to confer long-term protection. This suggests a population with insufficient or waning antibody that may be susceptible to breakthrough disease and transmission. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Endogenous Antibodies for Tumor Detection

    PubMed Central

    Rich, Barrie S.; Honeyman, Joshua N.; Darcy, David G.; Smith, Peter T.; Williams, Andrew R.; Lim, Irene Isabel P.; Johnson, Linda K.; Gönen, Mithat; Simon, Joel S.; LaQuaglia, Michael P.; Simon, Sanford M.

    2014-01-01

    The study of cancer immunology has provided diagnostic and therapeutic instruments through serum autoantibody biomarkers and exogenous monoclonal antibodies. While some endogenous antibodies are found within or surrounding transformed tissue, the extent to which this exists has not been entirely characterized. We find that in transgenic and xenograft mouse models of cancer, endogenous gamma immunoglobulin (IgG) is present at higher concentration in malignantly transformed organs compared to non-transformed organs in the same mouse or organs of cognate wild-type mice. The enrichment of endogenous antibodies within the malignant tissue provides a potential means of identifying and tracking malignant cells in vivo as they mutate and diversify. Exploiting these antibodies for diagnostic and therapeutic purposes is possible through the use of agents that bind endogenous antibodies. PMID:24875800

  11. Conference Summary

    NASA Astrophysics Data System (ADS)

    Sanders, David B.

    2014-07-01

    This conference on ``Multi-wavelength AGN Surveys and Studies'' has provided a detailed look at the explosive growth over the past decade, of available astronomical data from a growing list of large scale sky surveys, from radio-to-gamma rays. We are entering an era were multi-epoch (months to weeks) surveys of the entire sky, and near-instantaneous follow-up observations of variable sources, are elevating time-domain astronomy to where it is becoming a major contributor to our understanding of Active Galactic Nuclei (AGN). While we can marvel at the range of extragalactic phenomena dispayed by sources discovered in the original ``Markarian Survey'' - the first large-scale objective prism survey of the Northern Sky carried out at the Byurakan Astronomical Observtory almost a half-century ago - it is clear from the talks and posters presented at this meeting that the data to be be obtained over the next decade will be needed if we are to finally understand which phase of galaxy evolution each Markarian Galaxy represents.

  12. Complete mapping of viral escape from neutralizing antibodies

    PubMed Central

    Hensley, Scott E.

    2017-01-01

    Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein. This approach, mutational antigenic profiling, involves creating all replication-competent protein variants of a virus, selecting with antibody, and using deep sequencing to identify enriched mutations. We use mutational antigenic profiling to comprehensively identify mutations that enable influenza virus to escape four monoclonal antibodies targeting hemagglutinin, and validate key findings with neutralization assays. We find remarkable mutation-level idiosyncrasy in antibody escape: for instance, at a single residue targeted by two antibodies, some mutations escape both antibodies while other mutations escape only one or the other. Because mutational antigenic profiling rapidly maps all mutations selected by an antibody, it is useful for elucidating immune specificities and interpreting the antigenic consequences of viral genetic variation. PMID:28288189

  13. The Red Pen Revisited: Teaching Composition through Student Conferences.

    ERIC Educational Resources Information Center

    Fassler, Barbara

    1978-01-01

    Private conferences with students allow the composition teacher to give more feedback, increase teacher concentration and pace, demystify the evaluation process, and facilitate teacher/student interaction. (DD)

  14. Vaccination of mice with a modified Vaccinia Ankara (MVA) virus expressing the African horse sickness virus (AHSV) capsid protein VP2 induces virus neutralising antibodies that confer protection against AHSV upon passive immunisation.

    PubMed

    Calvo-Pinilla, Eva; de la Poza, Francisco; Gubbins, Simon; Mertens, Peter Paul Clement; Ortego, Javier; Castillo-Olivares, Javier

    2014-02-13

    In previous studies we showed that a recombinant Modified Vaccinia Ankara (MVA) virus expressing the protein VP2 of AHSV serotype 4 (MVA-VP2) induced virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR-/-) against challenge. We continued these studies and determined, in the IFNAR-/- mouse model, whether the antibody responses induced by MVA-VP2 vaccination play a key role in protection against AHSV. Thus, groups of mice were vaccinated with wild type MVA (MVA-wt) or MVA-VP2 and the antisera from these mice were used in a passive immunisation experiment. Donor antisera from (a) MVA-wt; (b) MVA-VP2 vaccinated; or (c) MVA-VP2 vaccinated and AHSV infected mice, were transferred to AHSV non-immune recipient mice. The recipients were challenged with virulent AHSV together with MVA-VP2 vaccinated and MVA-wt vaccinated control animals and the levels of protection against AHSV-4 were compared between all these groups. The results showed that following AHSV challenge, mice that were passively immunised with MVA-VP2 vaccinated antisera were highly protected against AHSV disease and had lower levels of viraemia than recipients of MVA-wt antisera. Our study indicates that MVA-VP2 vaccination induces a highly protective humoral immune response against AHSV.

  15. Antiparietal cell antibody test

    MedlinePlus

    APCA; Anti-gastric parietal cell antibody; Atrophic gastritis - anti-gastric parietal cell antibody; Gastric ulcer - anti-gastric parietal cell antibody; Pernicious anemia - anti-gastric parietal cell antibody; Vitamin B12 - anti-gastric ...

  16. Conference Scene

    PubMed Central

    Leeder, J Steven; Lantos, John; Spielberg, Stephen P

    2015-01-01

    A major challenge for clinicians, pharmaceutical companies and regulatory agencies is to better understand the relative contributions of ontogeny and genetic variation to observed variability in drug disposition and response across the pediatric age spectrum from preterm and term newborns, to infants, children and adolescents. Extrapolation of adult experience with pharmacogenomics and personalized medicine to pediatric patients of different ages and developmental stages, is fraught with many challenges. Compared with adults, pediatric pharmacogenetics and pharmacogenomics involves an added measure of complexity as variability owing to developmental processes, or ontogeny, is superimposed upon genetic variation. Furthermore, some pediatric diseases have no adult correlate or are more prevalent in children compared with adults, and several adverse drug reactions are unique to children, or occur at a higher frequency in children. The primary objective of this conference was to initiate an ongoing series of annual meetings on ‘Pediatric Pharmacogenomics and Personalized Medicine’ organized by the Center for Personalized Medicine and Therapeutic Innovation and Division of Clinical Pharmacology and Medical Therapeutics at Children’s Mercy Hospitals and Clinics in Kansas City, MO, USA. The primary goals of the inaugural meeting were: to bring together clinicians, basic and translational scientists and allied healthcare practitioners, and engage in a multi- and cross-disciplinary dialog aimed at implementing personalized medicine in pediatric settings; to provide a forum for the presentation and the dissemination of research related to the application of pharmacogenomic strategies to investigations of variability of drug disposition and response in children; to explore the ethical, legal and societal implications of pharmacogenomics and personalized medicine that are unique to children; and finally, to create networking opportunities for stimulating discussion

  17. The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study

    PubMed Central

    Moots, Robert J.; Xavier, Ricardo M.; Mok, Chi Chiu; Rahman, Mahboob U.; Tsai, Wen-Chan; Al-Maini, Mustafa H.; Pavelka, Karel; Mahgoub, Ehab; Kotak, Sameer; Korth-Bradley, Joan; Pedersen, Ron; Mele, Linda; Shen, Qi; Vlahos, Bonnie

    2017-01-01

    Objective To assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes. Methods This multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6–24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays ≤2 days before the next scheduled dose. Efficacy measurements included Disease Activity Score 28-joint count (DAS28), low disease activity (LDA), remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories of injection site/infusion reactions, serum sickness, and thromboembolic events were collected. Results Baseline demographics of the 595 patients (ETN: n = 200; ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of treatment was 14.6, 13.5, and 13.1 months for ETN, ADL, and IFX, respectively. All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4% patients treated with ADL and IFX, respectively, tested positive. In ADL- or IFX-treated patients, those with ADA had significantly lower trough drug concentrations. There were negative correlations between trough drug levels and both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission rates were higher in patients without ADA. The rate of targeted medical events reported was low. Conclusion ADA were detected in ADL- and IFX-treated but not ETN-treated patients. Patients without ADA generally showed numerically better clinical outcomes than those with ADA. Trial registration This study was registered on www.ClinicalTrials.gov (NCT01981473). PMID:28448562

  18. The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.

    PubMed

    Moots, Robert J; Xavier, Ricardo M; Mok, Chi Chiu; Rahman, Mahboob U; Tsai, Wen-Chan; Al-Maini, Mustafa H; Pavelka, Karel; Mahgoub, Ehab; Kotak, Sameer; Korth-Bradley, Joan; Pedersen, Ron; Mele, Linda; Shen, Qi; Vlahos, Bonnie

    2017-01-01

    To assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes. This multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6-24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays ≤2 days before the next scheduled dose. Efficacy measurements included Disease Activity Score 28-joint count (DAS28), low disease activity (LDA), remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories of injection site/infusion reactions, serum sickness, and thromboembolic events were collected. Baseline demographics of the 595 patients (ETN: n = 200; ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of treatment was 14.6, 13.5, and 13.1 months for ETN, ADL, and IFX, respectively. All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4% patients treated with ADL and IFX, respectively, tested positive. In ADL- or IFX-treated patients, those with ADA had significantly lower trough drug concentrations. There were negative correlations between trough drug levels and both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission rates were higher in patients without ADA. The rate of targeted medical events reported was low. ADA were detected in ADL- and IFX-treated but not ETN-treated patients. Patients without ADA generally showed numerically better clinical outcomes than those with ADA. This study was registered on www.ClinicalTrials.gov (NCT01981473).

  19. Antibody response in sheep following immunization with Streptococcus bovis in different adjuvants.

    PubMed

    Shu, Q; Bir, S H; Gill, H S; Duan, E; Xu, Y; Hiliard; Rowe, J B

    2001-01-01

    Recent studies have shown that immunization with Streptococcus bovis using Freund's complete adjuvant (FCA) may confer protection against lactic acidosis in sheep. The major objective of this study was to compare the antibody responses to S. bovis in a practically acceptable adjuvant (Freund's incomplete adjuvant (FIA); QuilA; dextran sulphate (Dex); Imject Alum; or Gerbu) and in FCA. Thirty-five sheep were randomly allocated to 7 treatment groups. Six groups were immunized with S. bovis in an adjuvant; the other group served as the non-immunization control. The primary immunization was administered intramuscularly on day 0. followed by a booster injection on day 28. Immunization with FCA induced the highest saliva and serum antibody responses. The saliva antibody concentrations in the FIA and QuilA groups were significantly higher than those in the Alum, Dex and Gerbu groups (p < 0.01). The serum antibody concentration in the FIA group was significantly higher than those in the QuilA, Alum. Dex and Gerbu groups (p < 0.01). Immunization enhanced the antibody level in faeces (p < 0.05), but there was no significant difference between the different adjuvant groups (p > 0.05). Seven and 14 days following booster immunization, the saliva antibody levels induced by QuilA and/or FIA were comparable with the level stimulated by FCA (p > 0.05). There was a strongly positive correlation (R2 = 0.770, p < 0.01) between the antibody concentrations in salival and serum. Compared with the controls, a higher faecal dry matter content was observed in the animals immunized with either FCA or QuilA. The change in faecal dry matter content was positively associated with the faecal antibody concentration (R2 = 0.441, p < 0.05). These results indicate that FIA and QuilA were effective at inducing high levels of antibody responses to S. bovis, and suggest that either Freund's incomplete adjuvant or QuilA may be useful for preparing a practically acceptable vaccine against lactic

  20. Reagents for astatination of biomolecules. 6. An intact antibody conjugated with a maleimido-closo-decaborate(2-) reagent via sulfhydryl groups had considerably higher kidney concentrations than the same antibody conjugated with an isothiocyanato-closo-decaborate(2-) reagent via lysine amines.

    PubMed

    Wilbur, D Scott; Chyan, Ming-Kuan; Nakamae, Hirohisa; Chen, Yun; Hamlin, Donald K; Santos, Erlinda B; Kornblit, Brian T; Sandmaier, Brenda M

    2012-03-21

    We are investigating the use of an (211)At-labeled anti-CD45 monoclonal antibody (mAb) as a replacement of total body irradiation in conditioning regimens designed to decrease the toxicity of hematopoietic cell transplantation (HCT). As part of that investigation, dose-escalation studies were conducted in dogs using (211)At-labeled anticanine CD45 mAb, CA12.10C12, conjugated with a maleimido-closo-decaborate(2-) derivative, 4. Unacceptable renal toxicity was noted in the dogs receiving doses in the 0.27-0.62 mCi/kg range. This result was not anticipated, as no toxicity had been noted in prior biodistribution and toxicity studies conducted in mice. Studies were conducted to understand the cause of the renal toxicity and to find a way to circumvent it. A dog biodistribution study was conducted with (123)I-labeled CA12.10C12 that had been conjugated with 4. The biodistribution data showed that 10-fold higher kidney concentrations were obtained with the maleimido-conjugate than had been obtained in a previous biodistribution study with (123)I-labeled CA12.10C12 conjugated with an amine-reactive phenylisothiocyanato-CHX-A″ derivative. The difference in kidney concentrations observed in dogs for the two conjugation approaches led to an investigation of the reagents. SE-HPLC analyses showed that the purity of the CA12.10C12 conjugated via reduced disulfides was lower than that obtained with amine-reactive conjugation reagents, and nonreducing SDS-PAGE analyses indicated protein fragments were present in the disulfide reduced conjugate. Although we had previously prepared closo-decaborate(2-) derivatives with amine-reactive functional groups (e.g., 6 and 8), a new, easily synthesized, amine-reactive (phenylisothiocyanate) derivative, 10, was prepared for use in the current studies. A biodistribution was conducted with coadministered (125)I- and (211)At-labeled CA12.10C10 conjugated with 10. In that study, lower kidney concentrations were obtained for both radionuclides

  1. Reagents for astatination of biomolecules. 6. An intact antibody conjugated with a maleimido-closo-decaborate(2-) reagent via sulfhydryl groups had considerably higher kidney concentrations than the same antibody conjugated with an isothiocyanato-closo-decaborate(2-) reagent via lysine amines

    PubMed Central

    Wilbur, D. Scott; Chyan, Ming-Kuan; Nakamae, Hirohisa; Chen, Yun; Hamlin, Donald K.; Santos, Erlinda B.; Kornblit, Brian T.; Sandmaier, Brenda M.

    2012-01-01

    We are investigating the use of an 211At-labeled anti-CD45 monoclonal antibody (mAb) as a replacement of total body irradiation in conditioning regimens designed to decrease the toxicity of hematopoietic cell transplantation (HCT). As part of that investigation, dose-escalation studies were conducted in dogs using 211At-labeled anti-canine CD45 mAb, CA12.10C12, conjugated with a maleimido-closo-decaborate(2-) derivative, 4. Unacceptable renal toxicity was noted in the dogs receiving doses in the 0.27 – 0.62 mCi/kg range. This result was not anticipated, as no toxicity had been noted in prior biodistribution and toxicity studies conducted in mice. Studies were conducted to understand the cause of the renal toxicity and to find a way to circumvent it. A dog biodistribution study was conducted with 123Ilabeled CA12.10C12 that had been conjugated with 4. The biodistribution data showed that 10-fold higher kidney concentrations were obtained with the maleimido-conjugate than had been obtained in a previous biodistribution study with 123I-labeled CA12.10C12 conjugated with an amine-reactive phenylisothiocyanato-CHX-A” derivative. The difference in kidney concentrations observed in dogs for the two conjugation approaches led to an investigation of the reagents. SE-HPLC analyses showed that the purity of the CA12.10C12 conjugated via reduced disulfides was lower than that obtained with amine-reactive conjugation reagents, and non-reducing SDS-PAGE analyses indicated protein fragments were present in the disulfide reduced conjugate. Although we had previously prepared closo-decaborate(2-) derivatives with amine-reactive functional groups (e.g. 6 & 8), a new easily synthesized, amine-reactive (phenylisothiocyanate) derivative, 10, was prepared for use in the current studies. A biodistribution was conducted with co-administered 125I- and 211At-labeled CA12.10C10 conjugated with 10. In that study, lower kidney concentrations were obtained for both radionuclides than had

  2. Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - prediction of viscosity through protein-protein interaction measurements.

    PubMed

    Neergaard, Martin S; Kalonia, Devendra S; Parshad, Henrik; Nielsen, Anders D; Møller, Eva H; van de Weert, Marco

    2013-06-14

    The purpose of this work was to explore the relation between protein-protein interactions (PPIs) and solution viscosity at high protein concentration using three monoclonal antibodies (mAbs), two of the IgG4 subclass and one of the IgG1 subclass. A range of methods was used to quantify the PPI either at low concentration (interaction parameter (kD) obtained from dynamic light scattering, DLS) or at high concentration (solution storage modulus (G') from ultrasonic shear rheology). We also developed a novel method for the determination of PPI using the apparent radius of the protein at either low or high protein concentration determined using DLS. The PPI measurements were correlated with solution viscosity (measured by DLS using polystyrene nanospheres and ultrasonic shear rheology) as a function of pH (4-9) and ionic strength (10, 50 and 150 mM). Our measurements showed that the highest solution viscosity was observed under conditions with the most negative kD, the highest apparent radius and the lowest net charge. An increase in ionic strength resulted in a change in the nature of the PPI at low pH from repulsive to attractive. In the neutral to alkaline pH region the mAbs behaved differently with respect to increase in ionic strength. Two mAbs (A and B) showed little or no effect of increasing ionic strength, whereas mAb-C showed a remarkable decrease in attractive PPI and viscosity. Previous studies have mainly investigated mAbs of the IgG₁ and IgG₂ subclass. We show here, for the first time, that mAbs of the IgG₄ subclass behave similar as the other subclasses. By comparison of the three tested mAbs with mAbs investigated in other studies a clear linear trend emerges between the pH of strongest attractive PPI and highest solution viscosity. The determination of PPI using either kD or apparent radius is thus a useful prediction tool in the determination of solution conditions that favors low solution viscosity at high protein concentration of

  3. Antibody engineering & therapeutics, the annual meeting of the antibody society December 7–10, 2015, San Diego, CA, USA

    PubMed Central

    Pauthner, Matthias; Yeung, Jenny; Ullman, Chris; Bakker, Joost; Wurch, Thierry; Reichert, Janice M.; Lund-Johansen, Fridtjof; Bradbury, Andrew R.M.; Carter, Paul J.; Melis, Joost P.M.

    2016-01-01

    ABSTRACT The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6–10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on “Antibodies to watch” in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries. PMID:26909869

  4. Antibodies against the majority subunit of type IV Pili disperse nontypeable Haemophilus influenzae biofilms in a LuxS-dependent manner and confer therapeutic resolution of experimental otitis media.

    PubMed

    Novotny, Laura A; Jurcisek, Joseph A; Ward, Michael O; Jordan, Zachary B; Goodman, Steven D; Bakaletz, Lauren O

    2015-04-01

    Despite resulting in a similar overall outcome, unlike antibodies directed against the DNABII protein, integration host factor (IHF), which induce catastrophic structural collapse of biofilms formed by nontypeable Haemophilus influenzae (NTHI), those directed against a recombinant soluble form of PilA [the majority subunit of Type IV pili (Tfp) produced by NTHI], mediated gradual 'top-down' dispersal of NTHI from biofilms. This dispersal occurred via a mechanism that was dependent upon expression of both PilA (and by inference, Tfp) and production of AI-2 quorum signaling molecules by LuxS. The addition of rsPilA to a biofilm-targeted therapeutic vaccine formulation comprised of IHF plus the powerful adjuvant dmLT and delivered via a noninvasive transcutaneous immunization route induced an immune response that targeted two important determinants essential for biofilm formation by NTHI. This resulted in significantly earlier eradication of NTHI from both planktonic and adherent populations in the middle ear, disruption of mucosal biofilms already resident within middle ears prior to immunization and rapid resolution of signs of disease in an animal model of experimental otitis media. These data support continued development of this novel combinatorial immunization approach for resolution and/or prevention of multiple diseases of the respiratory tract caused by NTHI.

  5. Antibodies against the majority subunit of Type IV pili disperse nontypeable Haemophilus influenzae biofilms in a LuxS-dependent manner and confer therapeutic resolution of experimental otitis media

    PubMed Central

    Novotny, Laura A.; Jurcisek, Joseph A.; Ward, Michael O.; Jordan, Zachary B.; Goodman, Steven D.; Bakaletz, Lauren O.

    2015-01-01

    Summary Despite resulting in a similar overall outcome, unlike antibodies directed against the DNABII protein, integration host factor (IHF), which induce catastrophic structural collapse of biofilms formed by nontypeable Haemophilus influenzae (NTHI), those directed against a recombinant soluble form of PilA [the majority subunit of Type IV pili (Tfp) produced by NTHI], mediated gradual ‘top-down’ dispersal of NTHI from biofilms. This dispersal occurred via a mechanism that was dependent upon expression of both PilA (and by inference, Tfp) and production of AI-2 quorum signaling molecules by LuxS. The addition of rsPilA to a biofilm-targeted therapeutic vaccine formulation comprised of IHF plus the powerful adjuvant dmLT, and delivered via a non-invasive transcutaneous immunization route, induced an immune response that targeted two important determinants essential for biofilm formation by NTHI. This resulted in significantly earlier eradication of NTHI from both planktonic and adherent populations in the middle ear, disruption of mucosal biofilms already resident within middle ears prior to immunization, and rapid resolution of signs of disease in an animal model of experimental otitis media. These data support continued development of this novel combinatorial immunization approach for resolution and/or prevention of multiple diseases of the respiratory tract caused by NTHI. PMID:25597921

  6. Conference Abstracts: AEDS '82.

    ERIC Educational Resources Information Center

    Journal of Computers in Mathematics and Science Teaching, 1982

    1982-01-01

    Abstracts from nine selected papers presented at the 1982 Association for Educational Data Systems (AEDS) conference are provided. Copies of conference proceedings may be obtained for fifteen dollars from the Association. (MP)

  7. Persistence of Group C Anticapsular Antibodies Two to Three Years After Immunization With an Investigational Quadrivalent Neisseria meningitidis-Diphtheria Toxoid Conjugate Vaccine

    PubMed Central

    Granoff, Dan M.; Morgan, Amy; Welsch, Jo Anne

    2005-01-01

    Background: An investigational quadrivalent (A, C, Y and W-135) meningococcal conjugate (MC-4) vaccine was reported to be more immunogenic in 2-year-olds than the currently licensed meningococcal polysaccharide vaccine, but persistence of serum antibody beyond 6 months after conjugate vaccination is unknown. Objective: Determine persistence and the immunologic basis of protective activity of group C anticapsular antibodies in sera obtained 2–3 years after MC-4 vaccination. Design: Group C antibody concentrations, bactericidal activity and passive protective activity were measured in sera from 48 children, ages 4–5 years, who had been immunized 2–3 years earlier with an MC-4 vaccine and from 47 children who had not been previously vaccinated. Results: Serum antibody concentrations were higher in the vaccinated than the unvaccinated children (geometric means, 0.30 and 0.09 μg/mL, respectively, P < 0.0001). Bactericidal titers ≥1/4 (considered protective) were infrequent in both vaccinated and unvaccinated children (14.6 and 6.4%, respectively, P = 0.3). Passive protective activity against bacteremia in the infant rat model was more frequent in sera from vaccinated (37.5%) than sera from unvaccinated children (12.5%, P < 0.02). The proportion of sera with passive protective activity increased with increasing anticapsular antibody concentrations (P < 0.0001). Interpretation: Serum group C antibody concentrations remained elevated for 2–3 years after MC-4 vaccination, and passive protective activity was more frequent in vaccinated than unvaccinated children. However, serum antibody concentrations in many vaccinated children were no longer sufficient to activate complement-mediated bacteriolysis in vitro or to confer passive protection against experimental group C disease. PMID:15702041

  8. Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro Improves Protection against Lentiviral Infection In Vivo

    PubMed Central

    Rudicell, Rebecca S.; Kwon, Young Do; Ko, Sung-Youl; Pegu, Amarendra; Louder, Mark K.; Georgiev, Ivelin S.; Wu, Xueling; Zhu, Jiang; Boyington, Jeffrey C.; Chen, Xuejun; Shi, Wei; Yang, Zhi-yong; Doria-Rose, Nicole A.; McKee, Krisha; O'Dell, Sijy; Schmidt, Stephen D.; Chuang, Gwo-Yu; Druz, Aliaksandr; Soto, Cinque; Yang, Yongping; Zhang, Baoshan; Zhou, Tongqing; Todd, John-Paul; Lloyd, Krissey E.; Eudailey, Joshua; Roberts, Kyle E.; Donald, Bruce R.; Bailer, Robert T.; Ledgerwood, Julie; Mullikin, James C.; Shapiro, Lawrence; Koup, Richard A.; Graham, Barney S.; Nason, Martha C.; Connors, Mark; Haynes, Barton F.; Rao, Srinivas S.; Roederer, Mario; Kwong, Peter D.

    2014-01-01

    protein was used to engineer a next-generation antibody with 5- to 8-fold increased potency in vitro. When administered to nonhuman primates, this antibody conferred protection at a 5-fold lower concentration than the original antibody. Our studies demonstrate an important correlation between in vitro assays used to evaluate the therapeutic potential of antibodies and their in vivo effectiveness. PMID:25142607

  9. Factors determining antibody distribution in tumors.

    PubMed

    Thurber, Greg M; Schmidt, Michael M; Wittrup, K Dane

    2008-02-01

    The development of antibody therapies for cancer is increasing rapidly, primarily owing to their specificity. Antibody distribution in tumors is often extremely uneven, however, leading to some malignant cells being exposed to saturating concentrations of antibody, whereas others are completely untargeted. This is detrimental because large regions of cells escape therapy, whereas other regions might be exposed to suboptimal concentrations that promote a selection of resistant mutants. The distribution of antibody depends on a variety of factors, including dose, affinity, antigens per cell and molecular size. Because these parameters are often known or easily estimated, a quick calculation based on simple modeling considerations can predict the uniformity of targeting within a tumor. Such analyses should enable experimental researchers to identify in a straightforward way the limitations in achieving evenly distributed antibody, and design and test improved antibody therapeutics more rationally.

  10. Parent Conferences. Beginnings Workshop.

    ERIC Educational Resources Information Center

    Duffy, Roslyn; And Others

    1997-01-01

    Presents six workshop sessions on parent conferences: (1) "Parents' Perspectives on Conferencing" (R. Duffy); (2) "Three Way Conferences" (G. Zeller); (3) "Conferencing with Parents of Infants" (K. Albrecht); (4) "Conferencing with Parents of School-Agers" (L. G. Miller); (5) "Cross Cultural Conferences" (J. Gonzalez-Mena); and (6) "Working with…

  11. EDITORIAL: Conference program

    NASA Astrophysics Data System (ADS)

    2006-04-01

    Some of the papers and talks given at the conference have not been published in this volume of Journal of Physics: Conference Series. The attached PDF file lists the full conference program and indicates (with an asterisk) those papers or talks which are not present in this volume.

  12. The General Conference Mennonites.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    General Conference Mennonites and Old Order Amish are compared and contrasted in the areas of physical appearance, religious beliefs, formal education, methods of farming, and home settings. General Conference Mennonites and Amish differ in physical appearance and especially in dress. The General Conference Mennonite men and women dress the same…

  13. Youth Conference Handbook.

    ERIC Educational Resources Information Center

    Brown, Brenda H.

    This handbook is designed to provide practical aid to those who have charge of the planning and organization of a youth conference, Defined as a conference to provide practical information as well as information about possible responsibilities, risks, and consequences of actions, related to the chosen conference topic. Suggestions are given for…

  14. Engineered antibodies take center stage.

    PubMed

    Huston, J S; George, A J

    2001-01-01

    The start of the post-genomic era provides a useful juncture for reflection on the state of antibody engineering, which will be a critical technology for relating function and pathology to genomic sequence in biology and medicine. The phenomenal progress in deciphering the human genome has given significant impetus to the application of engineered antibodies in proteomics. Thus, advances in phage display antibody libraries can now help to define novel gene function and the measurement of abnormal protein expression in pathological states. Furthermore, intrabody and antibody engineering provide vehicles for the development of molecular medicines of the future. In addition to these new directions, antibody engineering has begun to show concrete success in its long-term efforts to develop targeted immunotherapies for cancer and other diseases. The cornerstones of clinical development are the detailed academic clinical trials that continue to push the boundaries of engineered antibodies into the real world. The field displays a healthy impatience for practical results, as research accelerates with concerted efforts to transfer preclinical insights into clinical trials. Growing private and governmental expenditures will lead to the rapid expansion of life-saving immunotherapeutic agents. The present review developed from our effort to report on the 11th Annual International Conference on Antibody Engineering (3-6 December 2000). This annual meeting is a forum for discussions on the latest advances in antibody engineering groups from around the world, and now includes the broader agenda of engineering in molecular immunology. In bringing scientists together to exchange ideas at this open forum, new collaborations and the threads of new discoveries are woven. For example, Professors Gerhard Wagner (Harvard Medical School), Dennis Burton (Scripps Research Institute), and Peter Hudson (CSIRO, Melbourne, Australia) gave exciting insights on structural immunobiology that had

  15. Antibodies for immunoassays.

    PubMed

    Newman, D J

    2000-01-01

    What is an immunoassay without an antibody? Clearly the name provides the answer to this question; without antibodies there would be no immunoassays. An immunoassay is an analytical technique, quantitative or qualitative, that relies absolutely on the specificity and affinity of the interaction between epitope and paratope for generation of a detectable response. The actual detection of this binding interaction can be via one of literally hundreds of different signal transduction mechanisms, e.g., fluorimetry, chemiluminescence, agglutination (turbidimetry or nephelometry) enzyme reactions, and so forth (1 -4), but these are simply transducing systems for the primary binding interaction. Antibodies thus provide us with an exquisitely sensitive and specific analytical technology for detecting and quantifying epitopic structures. These structures include amino-acid derivatives, e.g., thyroid hormones, peptides, e.g., vasopressin, proteins, e.g., cytokines, as well as carbohydrate structures, e.g., CA-125. Immunoassay technology has developed to such an extent that it is probably the most versatile analytical tool available able to identify and quantify epitopic structures across the milli- to zeptomolar concentration ranges (2).

  16. [Improved IgG Antibody Diagnostics of Feather Duvet Lung by an Antibody Screening Test].

    PubMed

    Sennekamp, J; Lehmann, E

    2015-11-01

    The underdiagnosed feather duvet lung, an extrinsic allergic alveolitis (hypersensitivity pneumonitis) caused by duck and goose feathers, can be more frequently diagnosed, if duck and goose feather antibodies are included in the panel of the routinely applied IgG antibody screening test. This does not necessarily require extending the screening test to include duck and goose feather antigens. By analysing 100 sera with duck and goose antibodies we found that the commonly used pigeon and budgerigar antibodies can also screen for feather duvet antibodies. All examined sera lacking pigeon and budgerigar antibodies also lacked clear-cut duck and goose feather antibodies. The examined sera with strong pigeon or budgerigar antibodies always also contained feather duvet antibodies. However, sera with medium or low concentrated pigeon or budgerigar antibodies are not always associated with feather duvet antibodies. In the light of these observations, we find that 71% of the duck and goose antibody analyses would be dispensable without essential loss of quality, if the results of screening for pigeon and budgerigar antibodies were incorporated into the procedure of a step-by- step diagnostics.

  17. Boston Society's 11th Annual Applied Pharmaceutical Analysis conference.

    PubMed

    Lee, Violet; Liu, Ang; Groeber, Elizabeth; Moghaddam, Mehran; Schiller, James; Tweed, Joseph A; Walker, Gregory S

    2016-02-01

    Boston Society's 11th Annual Applied Pharmaceutical Analysis conference, Hyatt Regency Hotel, Cambridge, MA, USA, 14-16 September 2015 The Boston Society's 11th Annual Applied Pharmaceutical Analysis (APA) conference took place at the Hyatt Regency hotel in Cambridge, MA, on 14-16 September 2015. The 3-day conference affords pharmaceutical professionals, academic researchers and industry regulators the opportunity to collectively participate in meaningful and relevant discussions impacting the areas of pharmaceutical drug development. The APA conference was organized in three workshops encompassing the disciplines of regulated bioanalysis, discovery bioanalysis (encompassing new and emerging technologies) and biotransformation. The conference included a short course titled 'Bioanalytical considerations for the clinical development of antibody-drug conjugates (ADCs)', an engaging poster session, several panel and round table discussions and over 50 diverse talks from leading industry and academic scientists.

  18. Antibody binding loop insertions as diversity elements

    PubMed Central

    Kiss, Csaba; Fisher, Hugh; Pesavento, Emanuele; Dai, Minghua; Valero, Rosa; Ovecka, Milan; Nolan, Rhiannon; Phipps, M. Lisa; Velappan, Nileena; Chasteen, Leslie; Martinez, Jennifer S.; Waldo, Geoffrey S.; Pavlik, Peter; Bradbury, Andrew R.M.

    2006-01-01

    In the use of non-antibody proteins as affinity reagents, diversity has generally been derived from oligonucleotide-encoded random amino acids. Although specific binders of high-affinity have been selected from such libraries, random oligonucleotides often encode stop codons and amino acid combinations that affect protein folding. Recently it has been shown that specific antibody binding loops grafted into heterologous proteins can confer the specific antibody binding activity to the created chimeric protein. In this paper, we examine the use of such antibody binding loops as diversity elements. We first show that we are able to graft a lysozyme-binding antibody loop into green fluorescent protein (GFP), creating a fluorescent protein with lysozyme-binding activity. Subsequently we have developed a PCR method to harvest random binding loops from antibodies and insert them at predefined sites in any protein, using GFP as an example. The majority of such GFP chimeras remain fluorescent, indicating that binding loops do not disrupt folding. This method can be adapted to the creation of other nucleic acid libraries where diversity is flanked by regions of relative sequence conservation, and its availability sets the stage for the use of antibody loop libraries as diversity elements for selection experiments. PMID:17023486

  19. Antibody-based resistance to plant pathogens.

    PubMed

    Schillberg, S; Zimmermann, S; Zhang, M Y; Fischer, R

    2001-01-01

    Plant diseases are a major threat to the world food supply, as up to 15% of production is lost to pathogens. In the past, disease control and the generation of resistant plant lines protected against viral, bacterial or fungal pathogens, was achieved using conventional breeding based on crossings, mutant screenings and backcrossing. Many approaches in this field have failed or the resistance obtained has been rapidly broken by the pathogens. Recent advances in molecular biotechnology have made it possible to obtain and to modify genes that are useful for generating disease resistant crops. Several strategies, including expression of pathogen-derived sequences or anti-pathogenic agents, have been developed to engineer improved pathogen resistance in transgenic plants. Antibody-based resistance is a novel strategy for generating transgenic plants resistant to pathogens. Decades ago it was shown that polyclonal and monoclonal antibodies can neutralize viruses, bacteria and selected fungi. This approach has been improved recently by the development of recombinant antibodies (rAbs). Crop resistance can be engineered by the expression of pathogen-specific antibodies, antibody fragments or antibody fusion proteins. The advantages of this approach are that rAbs can be engineered against almost any target molecule, and it has been demonstrated that expression of functional pathogen-specific rAbs in plants confers effective pathogen protection. The efficacy of antibody-based resistance was first shown for plant viruses and its application to other plant pathogens is becoming more established. However, successful use of antibodies to generate plant pathogen resistance relies on appropriate target selection, careful antibody design, efficient antibody expression, stability and targeting to appropriate cellular compartments.

  20. Antibody Engineering & Therapeutics 2016: The Antibody Society's annual meeting, December 11-15, 2016, San Diego, CA.

    PubMed

    Larrick, James W; Alfenito, Mark R; Scott, Jamie K; Parren, Paul W H I; Burton, Dennis R; Bradbury, Andrew R M; Lemere, Cynthia A; Messer, Anne; Huston, James S; Carter, Paul J; Veldman, Trudi; Chester, Kerry A; Schuurman, Janine; Adams, Gregory P; Reichert, Janice M

    Antibody Engineering & Therapeutics, the largest meeting devoted to antibody science and technology and the annual meeting of The Antibody Society, will be held in San Diego, CA on December 11-15, 2016. Each of 14 sessions will include six presentations by leading industry and academic experts. In this meeting preview, the session chairs discuss the relevance of their topics to current and future antibody therapeutics development. Session topics include bispecifics and designer polyclonal antibodies; antibodies for neurodegenerative diseases; the interface between passive and active immunotherapy; antibodies for non-cancer indications; novel antibody display, selection and screening technologies; novel checkpoint modulators / immuno-oncology; engineering antibodies for T-cell therapy; novel engineering strategies to enhance antibody functions; and the biological Impact of Fc receptor engagement. The meeting will open with keynote speakers Dennis R. Burton (The Scripps Research Institute), who will review progress toward a neutralizing antibody-based HIV vaccine; Olivera J. Finn, (University of Pittsburgh School of Medicine), who will discuss prophylactic cancer vaccines as a source of therapeutic antibodies; and Paul Richardson (Dana-Farber Cancer Institute), who will provide a clinical update on daratumumab for multiple myeloma. In a featured presentation, a representative of the World Health Organization's INN expert group will provide a perspective on antibody naming. "Antibodies to watch in 2017" and progress on The Antibody Society's 2016 initiatives will be presented during the Society's special session. In addition, two pre-conference workshops covering ways to accelerate antibody drugs to the clinic and the applications of next-generation sequencing in antibody discovery and engineering will be held on Sunday December 11, 2016.

  1. Antibody Engineering & Therapeutics 2016: The Antibody Society's annual meeting, December 11–15, 2016, San Diego, CA

    PubMed Central

    Larrick, James W.; Alfenito, Mark R.; Scott, Jamie K.; Parren, Paul W. H. I.; Burton, Dennis R.; Bradbury, Andrew R. M.; Lemere, Cynthia A.; Messer, Anne; Huston, James S.; Carter, Paul J.; Veldman, Trudi; Chester, Kerry A.; Schuurman, Janine; Adams, Gregory P.; Reichert, Janice M.

    2016-01-01

    ABSTRACT Antibody Engineering & Therapeutics, the largest meeting devoted to antibody science and technology and the annual meeting of The Antibody Society, will be held in San Diego, CA on December 11-15, 2016. Each of 14 sessions will include six presentations by leading industry and academic experts. In this meeting preview, the session chairs discuss the relevance of their topics to current and future antibody therapeutics development. Session topics include bispecifics and designer polyclonal antibodies; antibodies for neurodegenerative diseases; the interface between passive and active immunotherapy; antibodies for non-cancer indications; novel antibody display, selection and screening technologies; novel checkpoint modulators / immuno-oncology; engineering antibodies for T-cell therapy; novel engineering strategies to enhance antibody functions; and the biological Impact of Fc receptor engagement. The meeting will open with keynote speakers Dennis R. Burton (The Scripps Research Institute), who will review progress toward a neutralizing antibody-based HIV vaccine; Olivera J. Finn, (University of Pittsburgh School of Medicine), who will discuss prophylactic cancer vaccines as a source of therapeutic antibodies; and Paul Richardson (Dana-Farber Cancer Institute), who will provide a clinical update on daratumumab for multiple myeloma. In a featured presentation, a representative of the World Health Organization's INN expert group will provide a perspective on antibody naming. “Antibodies to watch in 2017” and progress on The Antibody Society's 2016 initiatives will be presented during the Society's special session. In addition, two pre-conference workshops covering ways to accelerate antibody drugs to the clinic and the applications of next-generation sequencing in antibody discovery and engineering will be held on Sunday December 11, 2016. PMID:27557809

  2. [Antinuclear antibodies].

    PubMed

    Cabiedes, Javier; Núñez-Álvarez, Carlos A

    2010-01-01

    Anti-nuclear antibodies (ANA) are immunoglobulin directed against autologous cell nuclear and cytoplasmic components. Besides the autoimmune ANA there are other ANA that can be detected in circulation, like natural and infectious ANA. Because of its high sensibility, detection of the ANA must be done by indirect immunofluorescence (IIF) as screening test and all of those positive samples are convenient to confirm its specificity by ELISA, western blot or other techniques. Positive ANA detected by IIF must be evaluated taking in to account the pattern and titer. The following recommended step is the specificity characterization (reactivity against extractable nuclear antigens [ENA], dsDNA, etc.) which is useful for the diagnosis and follow up of patients with autoimmune diseases, and by such reasoning, its detection must be performed in an orderly and reasonable way using guides or strategies focused to the good use and interpretation of the autoantibodies. The objective of this review is to present a compilation of the literature and our experience in the detection and study of the ANA.

  3. Report on the AIDS Vaccine 2008 Conference.

    PubMed

    Alter, Galit; Ananworanich, Jintanat; Pantophlet, Ralph; Rybicki, Ed P; Buonaguro, Luigi

    2009-03-01

    The "AIDS Vaccine 2008" Conference was held in Cape Town, South Africa (October 13 to 16, 2008) and organized, under the aegis of the Global HIV Vaccine Enterprise, by Dr. Lynn Morris (Chair of the Conference) National Institute of Communicable Diseases; Dr. Koleka Mlisana from CAPRISA, University KwaZulu-Natal, Durban, Dr. Glenda Gray from Perinatal HIV Research Unit, University Witwatersrand, Johannesburg and Dr. Carolyn Williamson from Institute of Infectious Diseses. and Molecular Medicine, UCT, Cape Town (Co-Chairs of the Conference). Since the first AIDS Vaccine conference, organized in Paris in 2000, this was the first time it was held outside of the U.S. and Europe, and involved nearly 1,000 participants. Besides three Plenary Sessions with ten state-of-the-art plenary lectures and one Keynote Lecture given by Dr. A.S. Fauci (Director of NIAID, NIH, USA), the Conference was organized in nine oral sessions, four poster discussion groups covering a wide spectrum of scientific information relating to HIV vaccine research and development. Moreover three Symposia, two Special Sessions, one Roundtable as well as two Debates were held, the latter focusing on current controversial topics. The conference opening was memorable for a number of reasons: among these was the presence of South Africa's new Minister of Health, Barbara Hogan who, in her first speech in a major forum as a senior member of the SA Government, affirmed that HIV causes AIDS, and that the search for a vaccine is of paramount importance to SA and the rest of the world. A scientific summary of the Conference is reported in the present article, divided into four major topics: (1) vaccine concepts and design; (2) T-cell immunology and innate immunity; (3) B-cell immunology, neutralizing antibodies and mucosal immunology; and (4) clinical trials.

  4. Selection of antibodies from synthetic antibody libraries.

    PubMed

    Harel Inbar, Noa; Benhar, Itai

    2012-10-15

    More than 2 dozen years had passed since the field of antibody engineering was established, with the first reports of bacterial [1-3] and mammalian cells [4] expression of recombinant antibody fragments, and in that time a lot of effort was dedicated to the development of efficient technological means, intended to assist in the creation of therapeutic monoclonal antibodies (mAbs). Research focus was given to two intertwined technological aspects: the selection platform and the recombinant antibody repertoires. In accordance with these areas of interest, it is the goal of this chapter to describe the various selection tools and antibody libraries existing, with emphasis on the later, and their applications. This chapter gives a far from exhaustive, subjective "historic account" of the field, describing the selection platforms, the different formats of antibody repertoires and the applications of both for selecting recombinant antibodies. Several excellent books provide detailed protocols for constructing antibody libraries and selecting antibodies from those libraries [5-13]. Such books may guide a newcomer to the field in the fine details of antibody engineering. We would like to offer advice to the novice: although seemingly simple, effective library construction and antibody isolation provide best benefits in the hands of professionals. It is an art as much as it is science.

  5. Conference report: formulating better medicines for children: 4th European Paediatric Formulation Initiative conference.

    PubMed

    Walsh, Jennifer; Mills, Simon

    2013-01-01

    The fourth annual European Paediatric Formulation Initiative (EuPFI) conference on Formulating Better Medicines for Children was held on 19-20 September 2012 at the Institute of Molecular Genetics Congress Centre, Prague, Czech Republic. The 2-day conference concentrated on the latest advances, challenges and opportunities for developing medicinal products and administration devices for pediatric use, both from European and US perspectives. It was aimed specifically at providing exposure to emerging practical applications, and for illustrating remedies utilized by pediatric drug-development teams to overcome hurdles faced in developing medicines for pediatric patients. The conference format included plenary talks, focus sessions on each of the EuPFI work streams (extemporaneous preparations, excipients, pediatric administration devices, taste masking and taste assessment, age-appropriate formulations), case studies, soapbox sessions and a parallel poster display. This conference report summarizes the keynote lectures and also gives a flavor of other presentations and posters from the conference.

  6. 47 CFR 1.248 - Prehearing conferences; hearing conferences.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Prehearing conferences; hearing conferences. 1... Hearing Proceedings Prehearing Procedures § 1.248 Prehearing conferences; hearing conferences. (a) The... to appear at a specified time and place for a conference prior to a hearing, or to submit...

  7. Serum Concentrations of Antibodies against Outer Membrane Protein P6, Protein D, and T- and B-Cell Combined Antigenic Epitopes of Nontypeable Haemophilus influenzae in Children and Adults of Different Ages.

    PubMed

    Hua, Chun-Zhen; Hu, Wei-Lin; Shang, Shi-Qiang; Li, Jian-Ping; Hong, Li-Quan; Yan, Jie

    2015-12-16

    Nontypeable Haemophilus influenzae (NTHi) is one of the most common etiologies of acute otitis media, rhinosinusitis, and pneumonia. Outer membrane proteins (OMPs) are the main focus in new vaccine development against NTHi, as the H. influenzae type b (Hib) vaccine does not cover noncapsulated NTHi. The OMPs P6 and protein D are the most promising candidate antigens for an NTHi vaccine, and low antibody levels against them in serum may be correlated with infection caused by NTHi. In the current study, we measured the antibody titers against P6, protein D, and their T- and B-cell combined peptide epitopes in healthy individuals of different ages. We found that children <1 month old had the lowest antibody levels against NTHi P6, protein D, and their T- and B-cell combined antigenic epitopes. Antibody titers increased at ages 1 to 6 months, peaked at 7 months to 3 years, and remained high at 4 to 6 years. The antibody titers started to decrease after 6 years and were the lowest in the 21- to 30-year group. The geometric mean titers (GMTs) of T- and B-cell combined antigenic epitopes in P6 and protein D were positively correlated with those of the protein antigens. Among 12 peptides tested, P6-61, P6-123, and protein D-167 epitopes were better recognized than others in human serum. These findings might contribute to the development of an effective serotype-independent vaccine for H. influenzae.

  8. GE STEM Teacher's Conference

    NASA Image and Video Library

    2017-07-13

    Teachers participate in the Rocketry Engineering Design Challenge during the 2017 GE Foundation High School STEM Integration Conference at the Center for Space Education at NASA's Kennedy Space Center. High school teachers from across the country took part in the week-long conference, which is designed to explore effective ways for teachers, schools and districts from across the country to integrate STEM throughout the curriculum. The conference is a partnership between GE Foundation and the National Science Teachers Association.

  9. Stepwise engineering of heterodimeric single domain camelid VHH antibodies that passively protect mice from ricin toxin.

    PubMed

    Vance, David J; Tremblay, Jacqueline M; Mantis, Nicholas J; Shoemaker, Charles B

    2013-12-20

    In an effort to engineer countermeasures for the category B toxin ricin, we produced and characterized a collection of epitopic tagged, heavy chain-only antibody VH domains (VHHs) specific for the ricin enzymatic (RTA) and binding (RTB) subunits. Among the 20 unique ricin-specific VHHs we identified, six had toxin-neutralizing activity: five specific for RTA and one specific for RTB. Three neutralizing RTA-specific VHHs were each linked via a short peptide spacer to the sole neutralizing anti-RTB VHH to create VHH "heterodimers." As compared with equimolar concentrations of their respective monovalent monomers, all three VHH heterodimers had higher affinities for ricin and, in the case of heterodimer D10/B7, a 6-fold increase in in vitro toxin-neutralizing activity. When passively administered to mice at a 4:1 heterodimer:toxin ratio, D10/B7 conferred 100% survival in response to a 10 × LD50 ricin challenge, whereas a 2:1 heterodimer:toxin ratio conferred 20% survival. However, complete survival was achievable when the low dose of D10/B7 was combined with an IgG1 anti-epitopic tag monoclonal antibody, possibly because decorating the toxin with up to four IgGs promoted serum clearance. The two additional ricin-specific heterodimers, when tested in vivo, provided equal or greater passive protection than D10/B7, thereby warranting further investigation of all three heterodimers as possible therapeutics.

  10. Monoclonal antibodies and method for detecting dioxins and dibenzofurans

    DOEpatents

    Vanderlaan, Martin; Stanker, Larry H.; Watkins, Bruce E.; Bailey, Nina R.

    1989-01-01

    Compositions of matter are described which include five monoclonal antibodies that react with dioxins and dibenzofurans, and the five hybridomas that produce these monoclonal antibodies. In addition, a method for the use of these antibodies in a sensitive immunoassay for dioxins and dibenzofurans is given, which permits detection of these pollutants in samples at concentrations in the range of a few parts per billion.

  11. Antibody-mediated resistance against plant pathogens.

    PubMed

    Safarnejad, Mohammad Reza; Jouzani, Gholamreza Salehi; Tabatabaei, Meisam; Tabatabaie, Meisam; Twyman, Richard M; Schillberg, Stefan

    2011-01-01

    Plant diseases have a significant impact on the yield and quality of crops. Many strategies have been developed to combat plant diseases, including the transfer of resistance genes to crops by conventional breeding. However, resistance genes can only be introgressed from sexually-compatible species, so breeders need alternative measures to introduce resistance traits from more distant sources. In this context, genetic engineering provides an opportunity to exploit diverse and novel forms of resistance, e.g. the use of recombinant antibodies targeting plant pathogens. Native antibodies, as a part of the vertebrate adaptive immune system, can bind to foreign antigens and eliminate them from the body. The ectopic expression of antibodies in plants can also interfere with pathogen activity to confer disease resistance. With sufficient knowledge of the pathogen life cycle, it is possible to counter any disease by designing expression constructs so that pathogen-specific antibodies accumulate at high levels in appropriate sub-cellular compartments. Although first developed to tackle plant viruses and still used predominantly for this purpose, antibodies have been targeted against a diverse range of pathogens as well as proteins involved in plant-pathogen interactions. Here we comprehensively review the development and implementation of antibody-mediated disease resistance in plants.

  12. 76 FR 64083 - Reliability Technical Conference; Notice of Technical Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Reliability Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory Commission will hold a Technical Conference on Tuesday, November...

  13. Demonstration of the role of cytophilic antibody in resistance to malaria parasites (Plasmodium berghei) in rats.

    PubMed Central

    Green, T J; Kreier, J P

    1978-01-01

    This paper reports the results of a study of the nature of the immune response against Plasmodium berghei parasites by inbred rats. A macrophage-cytophilic antibody specific for malarial antigens was identified and characterized. Detection of the antibody on the macrophage surface was accomplished by the parasite adherence tests and by the indirect fluorescent antibody technique. Isolation and purification of the macrophage-cytophilic and opsonic antibodies from hyperimmune rat serum was accomplished by QAE-Sephadez A-50 elution chromatography, and of the macrophage-cytophilic antibody by adsorption with and elution from syngeneic macrophages as well. Characterization of the cytophilic antibody as immunoglobulin G1 was done by immunoelectrophoresis and by Ouchterlony-type double diffusion in gel. Passive protection tests in weanling inbred rats have demonstrated that the opsonizing antibody conferred some protection against P. berghei. The macrophage-cytophilic antibody, on the other hand, was not protective alone but acted synergistically with the opsonizing antibody. Images PMID:342408

  14. Recent advances using FcRn overexpression in transgenic animals to overcome impediments of standard antibody technologies to improve the generation of specific antibodies

    PubMed Central

    Cervenak, Judit; Erdei, Anna; Goldsby, Richard A; Butler, John E

    2011-01-01

    This review illustrates the salutary effects of neonatal Fc receptor (FcRn) overexpression in significantly improving humoral immune responses in the generation of antibodies for immunotherapy and diagnostics. These include: (1) improved IgG protection; (2) augmented antigen-specific humoral immune response with larger numbers of antigen specific B cells, thus offering a wider spectrum of clones; (3) generation of antibodies against weakly immunogenic antigens; (4) significant improvements in the number and substantial developments in the diversity of hybridomas. FcRn transgenesis thus confers a number of practical benefits, including faster antibody production, higher antibody yields and improved generation of hybridomas for monoclonal antibody production. Notably, these efficiencies in polyclonal antibody production were also demonstrated in FcRn transgenic rabbits. Overall, FcRn transgenic animals yield more antibodies and provide a route to the generation of antibodies against antigens of low immunogenicity that are difficult to obtain using currently available methods. PMID:22048692

  15. ASE Annual Conference 2010

    ERIC Educational Resources Information Center

    McCune, Roger

    2010-01-01

    In this article, the author describes the ASE Annual Conference 2010 which was held at Nottingham after a gap of 22 years. As always, the main conference was preceded by International Day, an important event for science educators from across the world. There were two strands to the programme: (1) "What works for me?"--sharing new ideas…

  16. District Leadership Conference Planner.

    ERIC Educational Resources Information Center

    Washington State Coordinating Council for Occupational Education, Olympia.

    This manual provides usable guidelines and planning forms and materials for planning district leadership conferences, which were designed and initiated in Washington State to meet the problems in student enrollment and, consequently, Distributive Education Clubs of America membership. The conferences have become a useful means to increase…

  17. [Conference Time Kit.

    ERIC Educational Resources Information Center

    National School Public Relations Association, Washington, DC.

    This multimedia kit, for use with and by teachers from kindergarten through the upper elementary grades, consists of four components: 1) a filmstrip for teachers; 2) the 1970 edition of a handbook, "Conference Time for Teachers and Parents"; 3) a filmstrip for parents; 4) a supporting parent information leaflet "How To Confer Successfully with…

  18. Facilitating Learning at Conferences

    ERIC Educational Resources Information Center

    Ravn, Ib; Elsborg, Steen

    2011-01-01

    The typical conference consists of a series of PowerPoint presentations that tend to render participants passive. Students of learning have long abandoned the transfer model that underlies such one-way communication. We propose an alternative theory of conferences that sees them as a forum for learning, mutual inspiration and human flourishing. We…

  19. The Learning Conference

    ERIC Educational Resources Information Center

    Ravn, Ib

    2007-01-01

    Purpose: The purpose of this paper is to call attention to the fact that conferences for professionals rely on massive one-way communication and hence produce little learning for delegates--and to introduce an alternative, the "learning conference", that involves delegates in fun and productive learning processes.…

  20. The Learning Conference

    ERIC Educational Resources Information Center

    Ravn, Ib

    2007-01-01

    Purpose: The purpose of this paper is to call attention to the fact that conferences for professionals rely on massive one-way communication and hence produce little learning for delegates--and to introduce an alternative, the "learning conference", that involves delegates in fun and productive learning processes.…

  1. Lyndon Johnson's Press Conferences.

    ERIC Educational Resources Information Center

    Cooper, Stephen

    Because President Lyndon Johnson understood well the publicity value of the American news media, he sought to exploit them. He saw reporters as "torch bearers" for his programs and policies and used the presidential press conference chiefly for promotional purposes. Although he met with reporters often, his press conferences were usually…

  2. ASE Annual Conference 2010

    ERIC Educational Resources Information Center

    McCune, Roger

    2010-01-01

    In this article, the author describes the ASE Annual Conference 2010 which was held at Nottingham after a gap of 22 years. As always, the main conference was preceded by International Day, an important event for science educators from across the world. There were two strands to the programme: (1) "What works for me?"--sharing new ideas…

  3. From Conference to Journal

    ERIC Educational Resources Information Center

    McCartney, Robert; Tenenberg, Josh

    2008-01-01

    Revising and extending conference articles for journal publication benefits both authors and readers. The new articles are more complete, and benefit from peer review, feedback from conference presentation, and greater editorial consistency. For those articles that are appropriate, we encourage authors to do this, and present two examples of such…

  4. Informing Selection of Nanomaterial Concentrations for ToxCast In Vitro Testing using the Multiple-Path Particle Dosimetry Model - 3rd Annual International Conference on the Environmental Implications of NanoTechnology (ICEIN) & EPA Nano Grantees Meeting (2011)

    EPA Science Inventory

    Currently, little justification is provided for nanomaterial testing concentrations in in vitro assays. The in vitro concentrations typically used may be higher than those experienced by exposed humans. Selection of concentration levels for hazard evaluation based on real-world e...

  5. Informing Selection of Nanomaterial Concentrations for ToxCast In Vitro Testing using the Multiple-Path Particle Dosimetry Model - 3rd Annual International Conference on the Environmental Implications of NanoTechnology (ICEIN) & EPA Nano Grantees Meeting (2011)

    EPA Science Inventory

    Currently, little justification is provided for nanomaterial testing concentrations in in vitro assays. The in vitro concentrations typically used may be higher than those experienced by exposed humans. Selection of concentration levels for hazard evaluation based on real-world e...

  6. Therapeutic assessment of SEED: a new engineered antibody platform designed to generate mono- and bispecific antibodies.

    PubMed

    Muda, Marco; Gross, Alec W; Dawson, Jessica P; He, Chaomei; Kurosawa, Emmi; Schweickhardt, Rene; Dugas, Melanie; Soloviev, Maria; Bernhardt, Anna; Fischer, David; Wesolowski, John S; Kelton, Christie; Neuteboom, Berend; Hock, Bjoern

    2011-05-01

    The strand-exchange engineered domain (SEED) platform was designed to generate asymmetric and bispecific antibody-like molecules, a capability that expands therapeutic applications of natural antibodies. This new protein engineered platform is based on exchanging structurally related sequences of immunoglobulin within the conserved CH3 domains. Alternating sequences from human IgA and IgG in the SEED CH3 domains generate two asymmetric but complementary domains, designated AG and GA. The SEED design allows efficient generation of AG/GA heterodimers, while disfavoring homodimerization of AG and GA SEED CH3 domains. Using a clinically validated antibody (C225), we tested whether Fab derivatives constructed on the SEED platform retain desirable therapeutic antibody features such as in vitro and in vivo stability, favorable pharmacokinetics, ligand binding and effector functions including antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. In addition, we tested SEED with combinations of binder domains (scFv, VHH, Fab). Mono- and bivalent Fab-SEED fusions retain full binding affinity, have excellent biochemical and biophysical stability, and retain desirable antibody-like characteristics conferred by Fc domains. Furthermore, SEED is compatible with different combinations of Fab, scFv and VHH domains. Our assessment shows that the new SEED platform expands therapeutic applications of natural antibodies by generating heterodimeric Fc-analog proteins.

  7. ICCK Conference Final Report

    SciTech Connect

    Green, William H.

    2013-05-28

    The 7th International Conference on Chemical Kinetics (ICCK) was held July 10-14, 2011, at Massachusetts Institute of Technology (MIT), in Cambridge, MA, hosted by Prof. William H. Green of MIT's Chemical Engineering department. This cross-disciplinary meeting highlighted the importance of fundamental understanding of elementary reactions to the full range of chemical investigations. The specific conference focus was on elementary-step kinetics in both the gas phase and in condensed phase. The meeting provided a unique opportunity to discuss how the same reactive species and reaction motifs manifest under very different reaction conditions (e.g. atmospheric, aqueous, combustion, plasma, in nonaqueous solvents, on surfaces.). The conference featured special sessions on new/improved experimental techniques, improved models and data analysis for interpreting complicated kinetics, computational kinetics (especially rate estimates for large kinetic models), and a panel discussion on how the community should document/archive kinetic data. In the past, this conference had been limited to homogeneous gas-phase and liquid-phase systems. This conference included studies of heterogeneous kinetics which provide rate constants for, or insight into, elementary reaction steps. This Grant from DOE BES covered about half of the subsidies we provided to students and postdocs who attended the conference, by charging them reduced-rate registration fees. The complete list of subsidies provided are listed in Table 1 below. This DOE funding was essential to making the conference affordable to graduate students, and indeed the attendance at this conference was higher than at previous conferences in this series. Donations made by companies provided additional subsidies, leveraging the DOE funding. The conference was very effective in educating graduate students and important in fostering scientific interactions, particularly between scientists studying gas phase and liquid phase kinetics

  8. Profiling antibodies to class II HLA in transplant patient sera.

    PubMed

    McMurtrey, Curtis; Lowe, Dave; Buchli, Rico; Daga, Sunil; Royer, Derek; Humphrey, Alisha; Cate, Steven; Osborn, Sean; Mojsilovic, Aleksandar; VanGundy, Rodney; Bardet, Wilfried; Duty, Andrew; Mojsilovic, Danijela; Jackson, Kenneth; Stastny, Peter; Briggs, David; Zehnder, Daniel; Higgins, Rob; Hildebrand, William

    2014-03-01

    Immunizing events including pregnancy, transfusions, and transplantation promote strong alloantibody responses to HLA. Such alloantibodies to HLA preclude organ transplantation, foster hyperacute rejection, and contribute to chronic transplant failure. Diagnostic antibody-screening assays detect alloreactive antibodies, yet key attributes including antibody concentration and isotype remain largely unexplored. The goal here was to provide a detailed profile of allogeneic antibodies to class II HLA. Methodologically, alloantibodies were purified from sensitized patient sera using an HLA-DR11 immunoaffinity column and subsequently categorized. Antibodies to DR11 were found to fix complement, exist at a median serum concentration of 2.3μg/mL, consist of all isotypes, and isotypes IgG2, IgM, and IgE were elevated. Because multimeric isotypes can confound diagnostic determinations of antibody concentration, IgM and IgA isotypes were removed and DR11-IgG tested alone. Despite removal of multimeric isotypes, patient-to-patient antibody concentrations did not correlate with MFI values. In conclusion, allogeneic antibody responses to DR11 are comprised of all antibody isotypes at differing proportions, these combined isotypes fix complement at nominal serum concentrations, and enhancements other than the removal of IgM and IgA multimeric isotypes may be required if MFI is to be used as a means of determining anti-HLA serum antibody concentrations in diagnostic clinical assays.

  9. Heterophilic antibodies as a source of error in immunoassay

    SciTech Connect

    Witherspoon, L.; Witkin, M.; Shuler, S.; Neely, H.; Gilbert, S.

    1985-05-01

    Antibodies directed against IgG used in an immunoassay, when present in patient serum, may lead to erroneous estimates of analyte by combining with the primary antibody and effectively reducing its concentration. In two patients with anti-rabbit IgG the authors obtained apparently elevated TSH, LH, and FSH estimates using competitive, second antibody kits Dilutional parallelism could not be demonstrated using these kits. Normal TSH estimates were obtained using one of several IRMAs and a competitive assay which included rabbit IgG in the buffer. Normal LH and FSH estimates (including dilutional parallelism) were obtained using competitive assay kits which included rabbit IgG in the buffer. The authors were not able to repair the antibody-limited kits by adding rabbit IgG, as the second antibody concentration was inadequate to precipitate the added IgG Heterophilic antibody directed against the assay antibody presents a significant potential problem in immunoassay. This problem is most pronounced in antibody limited systems and may be avoided by the addition of same-species IgG. The laboratory user may not be able to make this addition unless the separation step is reoptomized. Antibody excess (IRMA) systems are effected if the offending antibody is present in concentrations sufficient to saturate the extracting antibody. Practically, a heterophilic antibody must be suspected by demonstrating nonparallelism. This potential problem should be more widely appreciated.

  10. RABBIT ANTIBODIES TO STREPTOCOCCAL CARBOHYDRATES

    PubMed Central

    Braun, Dietmar G.; Eichmann, Klaus; Krause, Richard M.

    1969-01-01

    In a search for possible genetic factors which may influence the immune response to the streptococcal carbohydrates, over 100 rabbits have been immunized with streptococcal vaccines, and representative examples of high and low response pairs mated. The concentration of precipitins to the group—specific carbohydrates has been measured in the antisera following primary intravenous immunization with heat-killed streptococcal vaccines, Group A, Group A-variant, and Group C. For the majority of rabbits, the concentration of precipitins varied between 1 and 10 mg/ml of antiserum; while in the minority, it was between 11 and 32 mg/ml. The offspring of rabbits with high antibody levels had a significantly higher concentration of antibody than was seen in the offspring of rabbits of low response parents. Such data suggest that the magnitude of the immune response to these carbohydrate antigens is under some form of genetic control. Not uncommonly in rabbits with hyper-γ-globulinemia following primary immunization, the group-specific precipitins are the predominant component of the γ-globulin. An unusual feature of such components is that they are electrophoretically monodisperse, and possess individual antigenic specificity. In this respect they resemble the myeloma proteins. When a response of this sort is not seen after primary immunization, it may occur after secondary immunization. Therefore, prior exposure to the same or closely related antigen may also have an influence on the occurrence of high concentrations of such uniform antibodies. PMID:5766948

  11. 2012 HIV Diagnostics Conference: the molecular diagnostics perspective.

    PubMed

    Branson, Bernard M; Pandori, Mark

    2013-04-01

    2012 HIV Diagnostic Conference Atlanta, GA, USA, 12-14 December 2012. This report highlights the presentations and discussions from the 2012 National HIV Diagnostic Conference held in Atlanta (GA, USA), on 12-14 December 2012. Reflecting changes in the evolving field of HIV diagnostics, the conference provided a forum for evaluating developments in molecular diagnostics and their role in HIV diagnosis. In 2010, the HIV Diagnostics Conference concluded with the proposal of a new diagnostic algorithm which included nucleic acid testing to resolve discordant screening and supplemental antibody test results. The 2012 meeting, picking up where the 2010 meeting left off, focused on scientific presentations that assessed this new algorithm and the role played by RNA testing and new developments in molecular diagnostics, including detection of total and integrated HIV-1 DNA, detection and quantification of HIV-2 RNA, and rapid formats for detection of HIV-1 RNA.

  12. Third International Conference on Plant-Based Vaccines and Antibodies.

    PubMed

    Rybicki, Edward P

    2009-09-01

    This relatively new biennial meeting - the first was in Prague in 2005 - was chaired by Julian Ma (Guy's Hospital, London, UK), with Mario Pezzotti (University of Verona, Italy) as local organizer, and attracted approximately 180 delegates from 25 countries. The theme was 'Plant Expression Systems for Recombinant Pharmacologics': there were 46 talks gathered into two plenaries, 12 themed sessions and 72 posters. Topics covered included publicly funded and commercial developments, innovation, regulation and commercialization, competition with conventional technology, manufacture and new products.

  13. 1985 oil spill conference

    SciTech Connect

    Not Available

    1985-02-01

    This 1985 Oil Spill Conference, our ninth biennial meeting, presents another unique opportunity fo industry, government, and academic representatives to meet and exchange ideas to enhance our knowledge and understanding of the prevention, behavior, control, and cleanup of oil spills. Growing international and domestic participation, and the continued worldwide use of the Proceedings of past oil spill conferences as valuable reference sources affirms the importance and quality of these conferences. It is my firm belief, furthermore, that the conferences have contributed substantially to the reduction in the number of marine oil spills, and to our increased cleanup capabilities. The sponsoring organizations--the United States Coast Guard, the American Petroleum Institute, and the United States Environmental Protection Agency--have combined their efforts to provide a program of timely technical content which affords the opportunity to review the state-of-the-art accomplishments since our last conference in 1983. Finally, I hope that the knowledge and associations developed at this conference will influence your decision to participate in the 1987 Oil Spill Conference, to be held in Baltimore, Maryland.

  14. Antibodies and antibody-derived analytical biosensors

    PubMed Central

    Sharma, Shikha; Byrne, Hannah

    2016-01-01

    The rapid diagnosis of many diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Biosensors are now being applied for rapid diagnostics due to their capacity for point-of-care use with minimum need for operator input. Antibody-based biosensors or immunosensors have revolutionized diagnostics for the detection of a plethora of analytes such as disease markers, food and environmental contaminants, biological warfare agents and illicit drugs. Antibodies are ideal biorecognition elements that provide sensors with high specificity and sensitivity. This review describes monoclonal and recombinant antibodies and different immobilization approaches crucial for antibody utilization in biosensors. Examples of applications of a variety of antibody-based sensor formats are also described. PMID:27365031

  15. Antibody persistence and immunologic memory after sequential pneumococcal conjugate and polysaccharide vaccination in HIV-infected children on highly active antiretroviral therapy.

    PubMed

    Abzug, Mark J; Song, Lin Ye; Levin, Myron J; Nachman, Sharon A; Borkowsky, William; Pelton, Stephen I

    2013-10-01

    The capacity of pneumococcal vaccination to confer memory in HIV-infected children is critical for durable protection. HIV-infected children 2-<19 years administered two doses of pneumococcal conjugate vaccine (PCV7) and one dose of polysaccharide vaccine (PPV) on HAART were randomized 4-5 years later to receive a PCV7 or PPV booster. Total and high avidity antibodies to serotypes 1 (PPV) and 6B and 14 (PCV7 and PPV) were determined by ELISA. Memory was defined as persistence of ≥ 0.5 mcg/mL of serotype-specific antibody on day 0 or change from <0.5 mcg/mL to ≥ 0.5 mcg/mL between day 0 and week 1, or, ≥ 4-fold antibody rise between day 0 and week 1. Prior to boosting, 4-5 years after the previous PCV7-PCV7-PPV series, geometric mean concentrations (GMCs) were 0.46 mcg/mL (serotype 1), 1.31 mcg/mL (serotype 6B), and 1.47 mcg/mL (serotype 14), with concentrations ≥ 0.5 mcg/mL in 41% (serotype 1) to 82% (serotypes 6B and 14). Memory based on antibody concentration ≥ 0.5 mcg/mL before or 1 week after boosting with PCV7 or PPV was demonstrated in 42-61% for serotype 1 and 87-94% for serotypes 6B and 14, with lower rates based on day 0 to week 1 ≥ 4-fold antibody rise (serotype 1, 3-13%; serotype 6B, 13-31%; serotype 14, 29-53%). Antibody concentrations post-boosting were greater following PCV7 than PPV for serotypes 6B and 14. Ratios of highly avid to total antibody pre- and post-boosting were 0.5-0.8. Predictors of memory included higher CD4% (nadir before HAART and at P1024 and P1061s entry), CD19% (at P1024 and P1061s entry), and antibody response after the PCV7-PCV7-PPV primary series and lower viral load (at P1024 and P1061s entry) and age. Protective antibody concentrations, high avidity, and booster responses to PCV7 or PPV indicative of memory were present 4-5 years after PCV7-PCV7-PPV in HIV-infected children on HAART. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Antibody Persistence and Immunologic Memory after Sequential Pneumococcal Conjugate and Polysaccharide Vaccination in HIV-Infected Children on Highly Active Antiretroviral Therapy

    PubMed Central

    Abzug, Mark J.; Song, Lin Ye; Levin, Myron J.; Nachman, Sharon A.; Borkowsky, William; Pelton, Stephen I.

    2013-01-01

    Background The capacity of pneumococcal vaccination to confer memory in HIV-infected children is critical for durable protection. Methods HIV-infected children 2–<19 years administered two doses of pneumococcal conjugate vaccine (PCV7) and one dose of polysaccharide vaccine (PPV) on HAART were randomized four-five years later to receive a PCV7 or PPV booster. Total and high avidity antibodies to serotypes 1 (PPV) and 6B and 14 (PCV7 and PPV) were determined by ELISA. Memory was defined as persistence of ≥0.5 mcg/mL of serotype-specific antibody on day 0 or change from <0.5 mcg/mL to ≥0.5 mcg/mL between day 0 and week 1, or, ≥4-fold antibody rise between day 0 and week 1. Results Prior to boosting, four to five years after the previous PCV7-PCV7-PPV series, geometric mean concentrations (GMCs) were 0.46 mcg/mL (serotype 1), 1.31 mcg/mL (serotype 6B), and 1.47 mcg/mL (serotype 14), with concentrations ≥0.5 mcg/mL in 41% (serotype 1) to 82% (serotypes 6B and 14). Memory based on antibody concentration ≥0.5 mcg/mL before or 1 week after boosting with PCV7 or PPV was demonstrated in 42–61% for serotype 1 and 87–94% for serotypes 6B and 14, with lower rates based on day 0 to week 1 ≥4-fold antibody rise (serotype 1, 3–13%; serotype 6B, 13–31%; serotype 14, 29–53%). Antibody concentrations post-boosting were greater following PCV7 than PPV for serotypes 6B and 14. Ratios of highly avid to total antibody pre- and post-boosting were 0.5–0.8. Predictors of memory included higher CD4% (nadir before HAART and at P1024 and P1061s entry), CD19% (at P1024 and P1061s entry), and antibody response after the PCV7-PCV7-PPV primary series and lower viral load (at P1024 and P1061s entry) and age. Conclusions Protective antibody concentrations, high avidity, and booster responses to PCV7 or PPV indicative of memory were present four-five years after PCV7-PCV7-PPV in HIV-infected children on HAART. PMID:23954381

  17. Serum herpes simplex antibodies

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003352.htm Serum herpes simplex antibodies To use the sharing features on this page, please enable JavaScript. Serum herpes simplex antibodies is a blood test that looks for ...

  18. Platelet associated antibodies

    MedlinePlus

    ... medlineplus.gov/ency/article/003552.htm Platelet-associated antibodies blood test To use the sharing features on ... JavaScript. This blood test shows if you have antibodies against platelets in your blood. Platelets are a ...

  19. Conference Report: Wyoming Invitational Conference on Instructional Applications of Computers.

    ERIC Educational Resources Information Center

    Kansky, Bob

    This report: (1) describes the organization of an invitational conference aimed at gathering direction from classroom teachers regarding instructional applications of computers; (2) provides copies of all materials used in organizing such a conference; and (3) reports the results of the conference in terms of conference products (resolutions,…

  20. 48 CFR 6101.11 - Conferences; conference memorandum [Rule 11].

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Conferences; conference memorandum . 6101.11 Section 6101.11 Federal Acquisition Regulations System CIVILIAN BOARD OF CONTRACT APPEALS, GENERAL SERVICES ADMINISTRATION CONTRACT DISPUTE CASES 6101.11 Conferences; conference...

  1. GE STEM Teacher's Conference

    NASA Image and Video Library

    2017-07-13

    Teachers prepare to demonstrate the projects they built for the Rocketry Engineering Design Challenge during the 2017 GE Foundation High School STEM Integration Conference at the Center for Space Education at NASA's Kennedy Space Center. High school teachers from across the country took part in the week-long conference, which is designed to explore effective ways for teachers, schools and districts from across the country to integrate STEM throughout the curriculum. The conference is a partnership between GE Foundation and the National Science Teachers Association.

  2. GE STEM Teacher's Conference

    NASA Image and Video Library

    2017-07-13

    Education Specialists Lynn Dotson, left, of the NASA Public Engagement Center, and Lester Morales, right, of Texas State University's NASA STEM Educator Professional Development Collaborative, explain the Rocketry Engineering Design Challenge to teachers participating in the 2017 GE Foundation High School STEM Integration Conference at the Center for Space Education at NASA's Kennedy Space Center. High school teachers from across the country took part in the week-long conference, which is designed to explore effective ways for teachers, schools and districts from across the country to integrate STEM throughout the curriculum. The conference is a partnership between GE Foundation and the National Science Teachers Association.

  3. Conformational isomerism and the diversity of antibodies.

    PubMed Central

    Foote, J; Milstein, C

    1994-01-01

    The fact that one cell encodes a single antibody sequence does not necessarily mean that the resulting antibody folds into a single structure, although this is a common assumption. Here we challenge this view and suggest that many antibodies do not have a single conformation at the combining site. The basis for this proposal comes from the kinetic analysis of a set of murine hybridomas derived from defined stages of the immune response to 2-phenyl-5-oxazolone (Ox). Among them we have identified three antibodies that exhibit complex hapten-binding kinetics. We observed biphasic or triphasic reactions in stopped-flow fluorescence experiments, indicating that ligand binding involved isomerization, as well as associative steps. The existence of an equilibrium between at least two antibody conformations, with ligands binding preferentially to one form, was deduced from the variation with hapten concentration of the apparent rate of each phase. PMID:7937957

  4. Antibody gene transfer with adeno-associated viral vectors as a method for HIV prevention.

    PubMed

    Brady, Jacqueline M; Baltimore, David; Balazs, Alejandro B

    2017-01-01

    Broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) show great promise in HIV prevention as they are capable of potently neutralizing a considerable breadth of genetically diverse strains. Passive transfer of monoclonal bNAb proteins can confer protection in animal models of HIV infection at modest concentrations, inspiring efforts to develop an HIV vaccine capable of eliciting bNAb responses. However, these antibodies demonstrate high degrees of somatic mutation and other unique characteristics that may hinder the ability of conventional approaches to consistently and effectively produce bNAb analogs. As an alternative strategy, we and others have proposed vector-mediated gene transfer to generate long-term, systemic production of bNAbs in the absence of immunization. Herein, we review the use of adeno-associated virus (AAV) vectors for delivery of HIV bNAbs and antibody-like proteins and summarize both the advantages and disadvantages of this strategy as a method for HIV prevention.

  5. Hepatitis B surface antibody purification with hepatitis B surface antibody imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-L-tyrosine methyl ester) particles.

    PubMed

    Uzun, Lokman; Say, Ridvon; Unal, Serhat; Denizli, Adil

    2009-01-15

    Hepatitis B surface antibody imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-L-tyrosine methyl ester) particles were prepared for the purification of hepatitis B surface antibody from human plasma. N-methacryloyl-L-tyrosine methyl ester was chosen as a complexing agent for hepatitis B surface antibodies. Hepatitis B surface antibody imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-L-tyrosine methyl ester) particles were characterized by surface area measurements, swelling test, scanning electron microscopy, elemental analysis, and Fourier transform infrared spectroscopy. Ethylene glycol (1.0M) was used as desorption agent. Adsorption studies were performed from hepatitis B surface antibody and anti-hepatitis A antibody positive human plasma. Effects of antibody concentration, contact time, N-methacryloyl-L-tyrosine methyl ester content and temperature on the adsorption capacity were investigated. The amount of hepatitis B surface antibody adsorbed per unit mass increased with increasing hepatitis B surface antibody concentration, then reached saturation. Maximum hepatitis B surface antibody adsorption amount was 21.4 mIU/mg. Adsorption process reached the equilibrium in 60 min. Competitive adsorption of hepatitis B surface antibody, total anti-hepatitis A antibody and total immunoglobulin E was investigated for showing the selectivity. Hepatitis B surface antibody-imprinted particles could adsorb hepatitis B surface antibody 18.3 times more than anti-hepatitis A antibody and 2.2 times more than immunoglobulin E. It can be concluded that hepatitis B surface antibody-imprinted particles have significant selectivity for hepatitis B surface antibody.

  6. The 1991 International Aerospace and Ground Conference on Lightning and Static Electricity, volume 2

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The proceedings of the conference are reported. The conference focussed on lightning protection, detection, and forecasting. The conference was divided into 26 sessions based on research in lightning, static electricity, modeling, and mapping. These sessions spanned the spectrum from basic science to engineering, concentrating on lightning prediction and detection and on safety for ground facilities, aircraft, and aerospace vehicles.

  7. RBC Antibody Screen

    MedlinePlus

    ... Cell Antibody Screen Related tests: Direct Antiglobulin Test ; Blood Typing ; RBC Antibody Identification ; Type and Screen; Crossmatch All content on Lab Tests Online has been reviewed and approved by our Editorial Review Board . At a ... screen is used to screen an individual's blood for antibodies directed against red blood cell (RBC) ...

  8. Modeling Antibody Diversity.

    ERIC Educational Resources Information Center

    Baker, William P.; Moore, Cathy Ronstadt

    1998-01-01

    Understanding antibody structure and function is difficult for many students. The rearrangement of constant and variable regions during antibody differentiation can be effectively simulated using a paper model. Describes a hands-on laboratory exercise which allows students to model antibody diversity using readily available resources. (PVD)

  9. Modeling Antibody Diversity.

    ERIC Educational Resources Information Center

    Baker, William P.; Moore, Cathy Ronstadt

    1998-01-01

    Understanding antibody structure and function is difficult for many students. The rearrangement of constant and variable regions during antibody differentiation can be effectively simulated using a paper model. Describes a hands-on laboratory exercise which allows students to model antibody diversity using readily available resources. (PVD)

  10. Aircraft Engine Emissions. [conference

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A conference on a aircraft engine emissions was held to present the results of recent and current work. Such diverse areas as components, controls, energy efficient engine designs, and noise and pollution reduction are discussed.

  11. Expedition 52 Press Conference

    NASA Image and Video Library

    2017-07-10

    Expedition 52 flight engineer Randy Bresnik of NASA answers a reporter's question during a crew press conference at the Gagarin Cosmonaut Training Center (GCTC), Monday, July 10, 2017 in Star City, Russia. Photo Credit: (NASA/Bill Ingalls)

  12. STS-135 Press Conference

    NASA Image and Video Library

    2011-06-30

    JSC2011-E-060448 (30 June 2011) --- NASA astronaut Rex Walheim, STS-135 mission specialist, fields a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA

  13. Expedition 52 Press Conference

    NASA Image and Video Library

    2017-07-10

    Expedition 52 flight engineer Sergey Ryazanskiy of Roscosmos answers a reporter's question during a crew press conference at the Gagarin Cosmonaut Training Center (GCTC), Monday, July 10, 2017 in Star City, Russia. Photo Credit: (NASA/Bill Ingalls)

  14. STS-135 Press Conference

    NASA Image and Video Library

    2011-06-30

    JSC2011-E-060450 (30 June 2011) --- NASA astronaut Rex Walheim, STS-135 mission specialist, responds to a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA

  15. Expedition 32 Press Conference

    NASA Image and Video Library

    2012-07-13

    Quarantined Expedition 32 Canadian backup crewmember Chris Hadfield answers reporters questions from behind glass during a prelaunch press conference held at the Cosmonaut Hotel on Friday, July 13, 2012 in Baikonur, Kazakhstan. Photo Credit (NASA/Carla Cioffi)

  16. STS-134 Press Conference

    NASA Image and Video Library

    2011-03-24

    JSC2011-E-028493 (24 March 2011) --- NASA astronaut Mark Kelly, STS-134 commander, responds to a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA or National Aeronautics and Space Administration

  17. STS-135 Press Conference

    NASA Image and Video Library

    2011-06-30

    JSC2011-E-060415 (30 June 2011) --- NASA astronaut Sandy Magnus, STS-135 mission specialist, responds to a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA

  18. STS-135 Press Conference

    NASA Image and Video Library

    2011-06-30

    JSC2011-E-060445 (30 June 2011) --- NASA astronaut Sandy Magnus, STS-135 mission specialist, responds to a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA

  19. Expedition 52 Press Conference

    NASA Image and Video Library

    2017-07-10

    Expedition 52 flight engineer Paolo Nespoli of ESA answers a reporter's question during a crew press conference at the Gagarin Cosmonaut Training Center (GCTC), Monday, July 10, 2017 in Star City, Russia. Photo Credit: (NASA/Bill Ingalls)

  20. STS-134 Press Conference

    NASA Image and Video Library

    2011-03-24

    JSC2011-E-028492 (24 March 2011) --- NASA astronaut Greg Chamitoff, STS-134 mission specialist, fields a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA or National Aeronautics and Space Administration

  1. STS-135 Press Conference

    NASA Image and Video Library

    2011-06-30

    JSC2011-E-060413 (30 June 2011) --- NASA astronaut Chris Ferguson, STS-135 commander, responds to a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA

  2. Lunar & Planetary Science Conference.

    ERIC Educational Resources Information Center

    Warner, Jeffrey L.; And Others

    1982-01-01

    Summaries of different topics discussed at the Lunar and Planetary Science Conference are presented to provide updated information to nonplanetologists. Some topics include Venus, isotopes, chondrites, creation science, cosmic dust, cratering, moons and rings, igneous rocks, and lunar soil. (DC)

  3. Expedition 6 Press Conference

    NASA Image and Video Library

    2003-05-05

    Expedition 6 Commander Ken Bowersox, left and NASA International Space Station Science Officer Don Pettit speak during a press conference at the Gagarin Cosmonaut Training Center in Star City, Russia, Thursday, May 6, 2003. Photo Credit: (NASA/Bill Ingalls)

  4. Expedition 6 Press Conference

    NASA Image and Video Library

    2003-05-05

    Expedition 6 International Space Station Science Officer Don Pettit speaks during a press conference at the Gagarin Cosmonaut Training Center in Star City, Russia, Thursday, May 6, 2003. Photo Credit: (NASA/Bill Ingalls)

  5. Lunar & Planetary Science Conference.

    ERIC Educational Resources Information Center

    Warner, Jeffrey L.; And Others

    1982-01-01

    Summaries of different topics discussed at the Lunar and Planetary Science Conference are presented to provide updated information to nonplanetologists. Some topics include Venus, isotopes, chondrites, creation science, cosmic dust, cratering, moons and rings, igneous rocks, and lunar soil. (DC)

  6. STS-132 press conference

    NASA Image and Video Library

    2010-05-03

    JSC2010-E-063790 (3 May 2010) --- NASA astronaut Garrett Reisman, STS-132 mission specialist, fields a question from a reporter during an STS-132 preflight press conference at NASA's Johnson Space Center.

  7. STS-132 press conference

    NASA Image and Video Library

    2010-05-03

    JSC2010-E-063807 (3 May 2010) --- NASA astronaut Mike Good, STS-132 mission specialist, responds to a question from a reporter during an STS-132 preflight press conference at NASA's Johnson Space Center.

  8. STS-131 press conference

    NASA Image and Video Library

    2010-03-09

    JSC2010-E-038795 (9 March 2010) --- NASA astronaut Stephanie Wilson, STS-131 mission specialist, fields a question from a reporter during an STS-131 preflight press conference at NASA's Johnson Space Center.

  9. STS-132 press conference

    NASA Image and Video Library

    2010-05-03

    JSC2010-E-063799 (3 May 2010) --- NASA astronaut Steve Bowen, STS-132 mission specialist, fields a question from a reporter during an STS-132 preflight press conference at NASA's Johnson Space Center.

  10. STS-132 press conference

    NASA Image and Video Library

    2010-05-03

    JSC2010-E-063808 (3 May 2010) --- NASA astronaut Garrett Reisman, STS-132 mission specialist, responds to a question from a reporter during an STS-132 preflight press conference at NASA's Johnson Space Center.

  11. STS-131 press conference

    NASA Image and Video Library

    2010-03-09

    JSC2010-E-038797 (9 March 2010) --- NASA astronaut Rick Mastracchio, STS-131 mission specialist, responds to a question from a reporter during an STS-131 preflight press conference at NASA's Johnson Space Center.

  12. STS-132 press conference

    NASA Image and Video Library

    2010-05-03

    JSC2010-E-063797 (3 May 2010) --- NASA astronaut Steve Bowen, STS-132 mission specialist, fields a question from a reporter during an STS-132 preflight press conference at NASA's Johnson Space Center.

  13. STS-131 press conference

    NASA Image and Video Library

    2010-03-09

    JSC2010-E-038794 (9 March 2010) --- NASA astronaut Alan Poindexter, STS-131 commander, responds to a question from a reporter during an STS-131 preflight press conference at NASA's Johnson Space Center.

  14. STS-135 Press Conference

    NASA Image and Video Library

    2011-06-30

    JSC2011-E-060439 (30 June 2011) --- NASA astronaut Chris Ferguson, STS-135 commander, responds to a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA

  15. STS-131 press conference

    NASA Image and Video Library

    2010-03-09

    JSC2010-E-038799 (9 March 2010) --- NASA astronaut Clayton Anderson, STS-131 mission specialist, responds to a question from a reporter during an STS-131 preflight press conference at NASA's Johnson Space Center.

  16. Expedition 19 Press Conference

    NASA Image and Video Library

    2009-03-24

    Expedition 19 Flight Engineer Michael R. Barratt smiles at his family from a quarantined glass room after a press conference on Wednesday, March 25, 2009 at the Cosmonaut Hotel in Baikonur, Kazakhstan. Photo Credit: (NASA/Bill Ingalls)

  17. Insider conference tips

    NASA Astrophysics Data System (ADS)

    Tennant, Jill

    2012-01-01

    Attending an educator conference and its associated exhibit hall can be a rewarding experience for your brain. But if you keep in mind these insider's tips, your feet, arms, stomach, and wallet will also thank you.

  18. National COPD conference summary.

    PubMed

    Buist, A Sonia; Bailey, William; Hurd, Suzanne S

    2004-01-01

    The first National COPD Conference, sponsored by the US COPD Coalition was held in Arlington, Virginia on November 14-15, 2003. The theme for the conference was developed around the Department of Health and Human Services (DHHS) Healthy People 2010 goals for COPD and included plenary speeches, roundtable discussions, abstracts, and workshops on spirometry, patient/physician education materials, and home monitoring/telemetry. The goal was to bring together a multidisciplinary group to identify important issues relating to COPD in the United States, specifically the barriers to a wider recognition of the disease, and to develop an orchestrated action plan. Over 500 scientists, clinicians, respiratory therapists, nurses, patients, government officials, and representatives from pharmaceutical companies participated. This summary provides the recommendations from the conference that will be used to develop an action plan for the US COPD Coalition. It includes actions proposed by plenary speakers, roundtable faculty and conference participants.

  19. Tackling conference carbon footprints

    NASA Astrophysics Data System (ADS)

    Grozier, Jim

    2016-12-01

    In reply to Margaret Harris's Lateral Thoughts article "Putting my foot down", which discussed the challenges of attending a conference with a physical disability (October p76) and a subsequent letter by Anna Wood (November p18).

  20. DNA sequencing conference, 2

    SciTech Connect

    Cook-Deegan, R.M.; Venter, J.C.; Gilbert, W.; Mulligan, J.; Mansfield, B.K.

    1991-06-19

    This conference focused on DNA sequencing, genetic linkage mapping, physical mapping, informatics and bioethics. Several were used to study this sequencing and mapping. This article also discusses computer hardware and software aiding in the mapping of genes.

  1. Monoclonal Antibodies Attached to Carbon Nanotube Transistors for Paclitaxel Detection

    NASA Astrophysics Data System (ADS)

    Lee, Wonbae; Lau, Calvin; Richardson, Mark; Rajapakse, Arith; Weiss, Gregory; Collins, Philip; UCI, Molecular Biology; Biochemistry Collaboration; UCI, Departments of Physics; Astronomy Collaboration

    Paclitaxel is a naturally-occurring pharmaceutical used in numerous cancer treatments, despite its toxic side effects. Partial inhibition of this toxicity has been demonstrated using weakly interacting monoclonal antibodies (3C6 and 8A10), but accurate monitoring of antibody and paclitaxel concentrations remains challenging. Here, single-molecule studies of the kinetics of antibody-paclitaxel interactions have been performed using single-walled carbon nanotube field-effect transistors. The devices were sensitized with single antibody attachments to record the single-molecule binding dynamics of paclitaxel. This label-free technique recorded a range of dynamic interactions between the antibody and paclitaxel, and it provided sensitive paclitaxel detection for pM to nM concentrations. Measurements with two different antibodies suggest ways of extending this working range and uncovering the mechanistic differences among different antibodies.

  2. Antibody-controlled actuation of DNA-based molecular circuits

    NASA Astrophysics Data System (ADS)

    Engelen, Wouter; Meijer, Lenny H. H.; Somers, Bram; de Greef, Tom F. A.; Merkx, Maarten

    2017-02-01

    DNA-based molecular circuits allow autonomous signal processing, but their actuation has relied mostly on RNA/DNA-based inputs, limiting their application in synthetic biology, biomedicine and molecular diagnostics. Here we introduce a generic method to translate the presence of an antibody into a unique DNA strand, enabling the use of antibodies as specific inputs for DNA-based molecular computing. Our approach, antibody-templated strand exchange (ATSE), uses the characteristic bivalent architecture of antibodies to promote DNA-strand exchange reactions both thermodynamically and kinetically. Detailed characterization of the ATSE reaction allowed the establishment of a comprehensive model that describes the kinetics and thermodynamics of ATSE as a function of toehold length, antibody-epitope affinity and concentration. ATSE enables the introduction of complex signal processing in antibody-based diagnostics, as demonstrated here by constructing molecular circuits for multiplex antibody detection, integration of multiple antibody inputs using logic gates and actuation of enzymes and DNAzymes for signal amplification.

  3. EPOXI Mission Press Conference

    NASA Image and Video Library

    2010-11-18

    Michael A'Hearn, EPOXI Principal Investigator, University of Maryland, holds a plastic bottle containing ice to illustrate a point during a press conference, Thursday, Nov. 18, 2010, at NASA Headquarters in Washington. The press conference was held to discuss the Nov. 4 successful flyby of Comet Hartley 2 by NASA's EPOXI Mission Spacecraft. Images from the flyby provided scientists the most extensive observations of a comet in history. Photo Credit: (NASA/Paul E. Alers)

  4. EPOXI Mission Press Conference

    NASA Image and Video Library

    2010-11-18

    Dr. James Green, Director of Planetary Science, NASA Headquarters, at podium, speaks during a press conference, Thursday, Nov. 18, 2010, at NASA Headquarters in Washington. The press conference was held to discuss the Nov. 4 successful flyby of Comet Hartley 2 by NASA's EPOXI Mission Spacecraft. Images from the flyby provided scientists the most extensive observations of a comet in history. Photo Credit: (NASA/Paul E. Alers)

  5. Multiphoton processes: conference proceedings

    SciTech Connect

    Lambropoulos, P.; Smith, S.J.

    1984-01-01

    The chapters of this volume represent the invited papers delivered at the conference. They are arranged according to thermatic proximity beginning with atoms and continuing with molecules and surfaces. Section headings include multiphoton processes in atoms, field fluctuations and collisions in multiphoton process, and multiphoton processes in molecules and surfaces. Abstracts of individual items from the conference were prepared separately for the data base. (GHT)

  6. The antibody-enzyme analogy. Characterization of antibodies to phosphopyridoxyltyrosine derivatives.

    PubMed

    Raso, V; Stollar, B D

    1975-02-11

    Stable analogs of the crucial Schiff base intermediate of enzymatic and nonenzymatic pyridoxal phosphate catalysis have been used as haptens for induction of specific antibodies. N-(5-phosphopyridoxyl)-3'-amino-L-tyrosine and its conformationally distinct cyclized derivative resemble the Schiff base formed upon mixing tyrosine with pyridoxal phosphate. These compounds were covalently coupled to a protein carrier via the 3'-amino group so as to confer a prescribed orientation, with the coenzyme region farthest removed from the carrier. A third antigen, with the phosphopyridoxyl group alone as the hapten, was prepared by linkage of pyridoxal phosphate directly to free amino groups on the carrier protein. Antibodies elicited for each determinant were purified by means of appropriate affinity columns. Antibody heterogeneity was observed in that different species could be separated from a given serum by sequential elution from the affinity columns with 1 M sodium phosphate buffers of pH 7.6, 5.2, 2.6 and 1.5. In assays of quantitative precipitation, inhibition of precipitation, equilibrium dialysis, and fluorescence quenching, antibodies to the phosphopyridoxyltyrosine haptens showed specificity for the phosphorylated form of the coenzyme and binding activity for both the coenzyme and tyrosine portions of the hapten. Antibodies to the phosphopyridoxyl groups alone did not display a similar reactivity toward the tyrosine portion of the complex haptens. The cyclic and noncyclic conformations of the hapten were serologically distinct, as antibody to each reacted preferentially with the homologous form.

  7. Conference scene: DGVS spring conference 2009.

    PubMed

    Kolligs, Frank Thomas

    2009-10-01

    The 3rd annual DGVS Spring Conference of the German Society for Gastroenterology (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten) was held at the Seminaris Campus Hotel in Berlin, Germany, on 8-9 May, 2009. The conference was organized by Roland Schmid and Matthias Ebert from the Technical University of Munich, Germany. The central theme of the meeting was 'translational gastrointestinal oncology: towards personalized medicine and individualized therapy'. The conference covered talks on markers for diagnosis, screening and surveillance of colorectal cancer, targets for molecular therapy, response prediction in clinical oncology, development and integration of molecular imaging in gastrointestinal oncology and translational research in clinical trial design. Owing to the broad array of topics and limitations of space, this article will focus on biomarkers, response prediction and the integration of biomarkers into clinical trials. Presentations mentioned in this summary were given by Matthias Ebert (Technical University of Munich, Germany), Esmeralda Heiden (Epigenomics, Berlin, Germany), Frank Kolligs (University of Munich, Germany), Florian Lordick (University of Heidelberg, Germany), Hans Jorgen Nielsen (University of Copenhagen, Denmark), Anke Reinacher-Schick (University of Bochum, Germany), Christoph Röcken (University of Berlin, Germany), Wolff Schmiegel (University of Bochum, Germany) and Thomas Seufferlein (University of Halle, Germany).

  8. Coarse grained modeling of transport properties in monoclonal antibody solution

    NASA Astrophysics Data System (ADS)

    Swan, James; Wang, Gang

    Monoclonal antibodies and their derivatives represent the fastest growing segment of the bio pharmaceutical industry. For many applications such as novel cancer therapies, high concentration, sub-cutaneous injections of these protein solutions are desired. However, depending on the peptide sequence within the antibody, such high concentration formulations can be too viscous to inject via human derived force alone. Understanding how heterogenous charge distribution and hydrophobicity within the antibodies leads to high viscosities is crucial to their future application. In this talk, we explore a coarse grained computational model of therapeutically relevant monoclonal antibodies that accounts for electrostatic, dispersion and hydrodynamic interactions between suspended antibodies to predict assembly and transport properties in concentrated antibody solutions. We explain the high viscosities observed in many experimental studies of the same biologics.

  9. Nuclear Rocket Technology Conference

    NASA Technical Reports Server (NTRS)

    1966-01-01

    The Lewis Research Center has a strong interest in nuclear rocket propulsion and provides active support of the graphite reactor program in such nonnuclear areas as cryogenics, two-phase flow, propellant heating, fluid systems, heat transfer, nozzle cooling, nozzle design, pumps, turbines, and startup and control problems. A parallel effort has also been expended to evaluate the engineering feasibility of a nuclear rocket reactor using tungsten-matrix fuel elements and water as the moderator. Both of these efforts have resulted in significant contributions to nuclear rocket technology. Many successful static firings of nuclear rockets have been made with graphite-core reactors. Sufficient information has also been accumulated to permit a reasonable Judgment as to the feasibility of the tungsten water-moderated reactor concept. We therefore consider that this technoIogy conference on the nuclear rocket work that has been sponsored by the Lewis Research Center is timely. The conference has been prepared by NASA personnel, but the information presented includes substantial contributions from both NASA and AEC contractors. The conference excludes from consideration the many possible mission requirements for nuclear rockets. Also excluded is the direct comparison of nuclear rocket types with each other or with other modes of propulsion. The graphite reactor support work presented on the first day of the conference was partly inspired through a close cooperative effort between the Cleveland extension of the Space Nuclear Propulsion Office (headed by Robert W. Schroeder) and the Lewis Research Center. Much of this effort was supervised by Mr. John C. Sanders, chairman for the first day of the conference, and by Mr. Hugh M. Henneberry. The tungsten water-moderated reactor concept was initiated at Lewis by Mr. Frank E. Rom and his coworkers. The supervision of the recent engineering studies has been shared by Mr. Samuel J. Kaufman, chairman for the second day of the

  10. Antibody Therapeutics in Oncology

    PubMed Central

    Wold, Erik D; Smider, Vaughn V; Felding, Brunhilde H

    2016-01-01

    One of the newer classes of targeted cancer therapeutics is monoclonal antibodies. Monoclonal antibody therapeutics are a successful and rapidly expanding drug class due to their high specificity, activity, favourable pharmacokinetics, and standardized manufacturing processes. Antibodies are capable of recruiting the immune system to attack cancer cells through complement-dependent cytotoxicity or antibody dependent cellular cytotoxicity. In an ideal scenario the initial tumor cell destruction induced by administration of a therapeutic antibody can result in uptake of tumor associated antigens by antigen-presenting cells, establishing a prolonged memory effect. Mechanisms of direct tumor cell killing by antibodies include antibody recognition of cell surface bound enzymes to neutralize enzyme activity and signaling, or induction of receptor agonist or antagonist activity. Both approaches result in cellular apoptosis. In another and very direct approach, antibodies are used to deliver drugs to target cells and cause cell death. Such antibody drug conjugates (ADCs) direct cytotoxic compounds to tumor cells, after selective binding to cell surface antigens, internalization, and intracellular drug release. Efficacy and safety of ADCs for cancer therapy has recently been greatly advanced based on innovative approaches for site-specific drug conjugation to the antibody structure. This technology enabled rational optimization of function and pharmacokinetics of the resulting conjugates, and is now beginning to yield therapeutics with defined, uniform molecular characteristics, and unprecedented promise to advance cancer treatment. PMID:27081677

  11. Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids.

    PubMed

    Handisurya, A; Schellenbacher, C; Haitel, A; Senger, T; Kirnbauer, R

    2016-02-16

    Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx.

  12. Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids

    PubMed Central

    Handisurya, A; Schellenbacher, C; Haitel, A; Senger, T; Kirnbauer, R

    2016-01-01

    Background: Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. Methods: We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. Results: HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. Conclusions: We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx. PMID:26867163

  13. Gamma Interferon Is Required for Optimal Antibody-Mediated Immunity against Genital Chlamydia Infection

    PubMed Central

    Naglak, Elizabeth K.; Morrison, Sandra G.

    2016-01-01

    Defining the mechanisms of immunity conferred by the combination of antibody and CD4+ T cells is fundamental to designing an efficacious chlamydial vaccine. Using the Chlamydia muridarum genital infection model of mice, which replicates many features of human C. trachomatis infection and avoids the characteristic low virulence of C. trachomatis in the mouse, we previously demonstrated a significant role for antibody in immunity to chlamydial infection. We found that antibody alone was not protective. Instead, protection appeared to be conferred through an undefined antibody-cell interaction. Using gene knockout mice and in vivo cellular depletion methods, our data suggest that antibody-mediated protection is dependent on the activation of an effector cell population in genital tract tissues by CD4+ T cells. Furthermore, the CD4+ T cell-secreted cytokine gamma interferon (IFN-γ) was found to be a key component of the protective antibody response. The protective function of IFN-γ was not related to the immunoglobulin class or to the magnitude of the Chlamydia-specific antibody response or to recruitment of an effector cell population to genital tract tissue. Rather, IFN-γ appears to be necessary for activation of the effector cell population that functions in antibody-mediated chlamydial immunity. Our results confirm the central role of antibody in immunity to chlamydia reinfection and demonstrate a key function for IFN-γ in antibody-mediated protection. PMID:27600502

  14. Antibodies in Transplantation

    PubMed Central

    Platt, Jeffrey L.

    2011-01-01

    Transplantation of cells, tissues, and organs from one individual to another can incite the production of antibodies specific for foreign antigens, especially major histocompatibility antigens, in the graft. Antibodies specific for a graft provide an index of immunity and a potential trigger for injury and rejection. However, the index of immunity can sometimes miss antibody-mediated rejection and besides causing injury the antibodies against a graft can also protect a graft from injury by blocking immune recognition, called enhancement, regulating activation of complement, and inducing changes in the graft that resist damage. Reviewed here are potential limitations in the use of antibodies as an index of immunity and the ways antibodies cause and/or prevent injury. PMID:20807473

  15. Demystified...recombinant antibodies.

    PubMed

    Smith, K A; Nelson, P N; Warren, P; Astley, S J; Murray, P G; Greenman, J

    2004-09-01

    Recombinant antibodies are important tools for biomedical research and are increasingly being used as clinical diagnostic/therapeutic reagents. In this article, a background to humanized antibodies is given, together with details of the generation of antibody fragments--for example, single chain Fv fragments. Phage antibody fragments are fast becoming popular and can be generated by simple established methods of affinity enrichment from libraries derived from immune cells. Phage display methodology can also be used for the affinity enrichment of existing antibody fragments to provide a reagent with a higher affinity. Here, phage antibodies are demystified to provide a greater understanding of the potential of these reagents and to engage clinicians and biomedical scientists alike to think about potential applications in pathology and clinical settings.

  16. Male Partner Risk Behaviors Are Associated With Reactive Rapid HIV Antibody Tests Among Pregnant Mexican Women: Implications for Prevention of Vertical and Sexual HIV Transmission in Concentrated HIV Epidemics.

    PubMed

    Rivero, Estela; Kendall, Tamil

    2015-01-01

    Mexico's policies on antenatal HIV testing are contradictory, and little is known about social and behavioral characteristics that increase pregnant Mexican women's risks of acquiring HIV. We analyzed the association between risk behaviors reported by pregnant women for themselves and their male partners, and women's rapid HIV antibody test results from a large national sample. Three quarters of pregnant women with a reactive test did not report risk behaviors for themselves and one third did not report risk behaviors for themselves or their male partners. In the retrospective case-control analysis, other than reporting multiple sexual partners, reactive pregnant women reported risk behaviors did not differ from nonreactive women's behaviors. However, reactive pregnant women were significantly more likely to have reported risk behaviors for male partners. Our findings support universal offer of antenatal HIV testing and suggest that HIV prevention for women should focus on reducing risk of HIV acquisition within stable relationships.

  17. Developing recombinant antibodies for biomarker detection

    SciTech Connect

    Baird, Cheryl L.; Fischer, Christopher J.; Pefaur, Noah B.; Miller, Keith D.; Kagen, Jacob; Srivastava, Sudhir; Rodland, Karin D.

    2010-10-01

    Monoclonal antibodies (mAbs) have an essential role in biomarker validation and diagnostic assays. A barrier to pursuing these applications is the reliance on immunization and hybridomas to produce mAbs, which is time-consuming and may not yield the desired mAb. We recommend a process flow for affinity reagent production that utilizes combinatorial protein display systems (eg, yeast surface display or phage display) rather than hybridomas. These systems link a selectable phenotype-binding conferred by an antibody fragment-with a means for recovering the encoding gene. Recombinant libraries obtained from immunizations can produce high-affinity antibodies (<10 nM) more quickly than other methods. Non-immune libraries provide an alternate route when immunizations are not possible, or when suitable mAbs are not recovered from an immune library. Directed molecular evolution (DME) is an integral part of optimizing mAbs obtained from combinatorial protein display, but can also be used on hybridoma-derived mAbs. Variants can easily be obtained and screened to increase the affinity of the parent mAb (affinity maturation). We discuss examples where DME has been used to tailor affinity reagents to specific applications. Combinatorial protein display also provides an accessible method for identifying antibody pairs, which are necessary for sandwich-type diagnostic assays.

  18. Immunometric Double-Antibody Sandwich Enzyme-Linked Immunosorbent Assay.

    PubMed

    Kohl, Thomas O; Ascoli, Carl A

    2017-06-01

    The double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) is preferentially used to determine the concentration of unknown antibody in a sample. Pure antigen is not required in this assay; however, the use of a reporter-labeled detection antibody is essential. The double-antibody sandwich ELISA is suitable for epitope mapping of different monoclonal antibodies that have been generated against a single antigen. First, plates are coated with a capture antibody specific for immunoglobulins generated by immunization of a host species. Next, the test antibody solution (e.g., serum) is incubated with the capture antibody to facilitate binding. The plates are washed to remove unbound antibody, and then antigen is added. The plates are washed again followed by the addition of an antigen-specific reporter-labeled antibody. Following incubation, unbound reporter antibody is washed off, and reporter-specific substrate is added. Reporter-mediated substrate hydrolysis is visualized and measured. The signal is proportional to the number of test antibodies present in the serum. © 2017 Cold Spring Harbor Laboratory Press.

  19. Overcoming the susceptibility gap between maternal antibody disappearance and auto-antibody production.

    PubMed

    Yosipovich, Roni; Aizenshtein, Elina; Shadmon, Roy; Krispel, Simcha; Shuster, Efrat; Pitcovski, Jacob

    2015-01-09

    In the first 10-14 days of a chick's life, protection is conferred by maternal antibodies. Further broiler protection is achieved by active vaccination. However, the high level of maternal antibodies interferes with the induction of an effective immune response by vaccination at a young age. As a result, there is a gap between the reduction in protective maternal antibodies and elevation of self-produced antibodies following active vaccination. The major aim of this study was to test an approach consisting of passive and active vaccination to overcome this gap and to provide continuous resistance to infectious viral diseases during the broiler's growth period. Newcastle disease virus (NDV), which is one of the world's most prevalent infectious diseases of poultry, was tested as a model. Following subcutaneous injection of 18 hemagglutination-inhibiting (HI) units of anti-NDV immunoglobulin Y per 1-day-old chick, protective log2 antibody titers above 4 could be detected to at least 17 days of age. The combination of passive immunization on day 1 of age with attenuated live vaccination on day 10 led to high protective titers throughout the entire growth period, up to 41 days of age. Moreover, the HI titers in the group of birds immunized with the combined vaccination were significantly more homogeneous than those in the group vaccinated only with live virus. Thus, full protection against NDV of all broilers in flock during their entire growth period was achieved by a vaccination regime that combines passive immunization and live vaccination.

  20. 10 CFR 501.32 - Conferences (other than prepetition conferences).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Conferences (other than prepetition conferences). 501.32 Section 501.32 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS ADMINISTRATIVE PROCEDURES AND SANCTIONS Written Comments, Public Hearings and Conferences During Administrative Proceedings § 501.32...

  1. 10 CFR 501.32 - Conferences (other than prepetition conferences).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Conferences (other than prepetition conferences). 501.32 Section 501.32 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS ADMINISTRATIVE PROCEDURES AND SANCTIONS Written Comments, Public Hearings and Conferences During Administrative Proceedings § 501.32...

  2. 10 CFR 501.32 - Conferences (other than prepetition conferences).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Conferences (other than prepetition conferences). 501.32 Section 501.32 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS ADMINISTRATIVE PROCEDURES AND SANCTIONS Written Comments, Public Hearings and Conferences During Administrative Proceedings § 501.32...

  3. 10 CFR 501.32 - Conferences (other than prepetition conferences).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Conferences (other than prepetition conferences). 501.32 Section 501.32 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS ADMINISTRATIVE PROCEDURES AND SANCTIONS Written Comments, Public Hearings and Conferences During Administrative Proceedings § 501.32...

  4. 10 CFR 501.32 - Conferences (other than prepetition conferences).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Conferences (other than prepetition conferences). 501.32 Section 501.32 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS ADMINISTRATIVE PROCEDURES AND SANCTIONS Written Comments, Public Hearings and Conferences During Administrative Proceedings § 501.32...

  5. 78 FR 27963 - Reliability Technical Conference; Notice of Technical Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Reliability Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory Commission will hold a Technical Conference on Tuesday, July 9,...

  6. A Simple Model for Assessment of Anti-Toxin Antibodies

    PubMed Central

    Skvortsov, Alex; Gray, Peter

    2013-01-01

    The toxins associated with infectious diseases are potential targets for inhibitors which have the potential for prophylactic or therapeutic use. Many antibodies have been generated for this purpose, and the objective of this study was to develop a simple mathematical model that may be used to evaluate the potential protective effect of antibodies. This model was used to evaluate the contributions of antibody affinity and concentration to reducing antibody-receptor complex formation and internalization. The model also enables prediction of the antibody kinetic constants and concentration required to provide a specified degree of protection. We hope that this model, once validated experimentally, will be a useful tool for in vitro selection of potentially protective antibodies for progression to in vivo evaluation. PMID:23862138

  7. Immunometric Antibody Sandwich Enzyme-Linked Immunosorbent Assay.

    PubMed

    Kohl, Thomas O; Ascoli, Carl A

    2017-06-01

    The antibody sandwich enzyme-linked immunosorbent assay (ELISA) is the most commonly used assay for rapid and accurate detection of antigens. It displays greater sensitivity compared with the indirect ELISA and can be used to determine absolute antigen concentrations in unknown samples provided purified antigen standards are available, although it requires the use of two different antibodies. Briefly, wells are coated with antigen-specific capture antibody then incubated with samples containing unknown antigen. Washing removes unbound antigen and exogenous sample protein before incubation with a second antigen-specific detection antibody, washing, and reincubation with a reporter-labeled tertiary antibody. After tertiary antibody is washed off, substrate is added and hydrolysis is measured spectrophotometrically. The signal intensity is directly proportional to the concentration of the antigen in the test sample. © 2017 Cold Spring Harbor Laboratory Press.

  8. ARC Conference Showcases Telecommunications Services.

    ERIC Educational Resources Information Center

    Baldwin, Fred D.

    1996-01-01

    The Appalachian Regional Commission's 1996 Conference, "Building Blocks for Using Telecommunications and Information Technology," held in Binghamton, New York, focused on the role of telecommunications in Appalachia in education and training, telemedicine, business, and government. Highlights conference presentations on special…

  9. ARC Conference Showcases Telecommunications Services.

    ERIC Educational Resources Information Center

    Baldwin, Fred D.

    1996-01-01

    The Appalachian Regional Commission's 1996 Conference, "Building Blocks for Using Telecommunications and Information Technology," held in Binghamton, New York, focused on the role of telecommunications in Appalachia in education and training, telemedicine, business, and government. Highlights conference presentations on special…

  10. Turbomachinery controls conference (TCC) 1995

    SciTech Connect

    1995-09-01

    The proceedings of the Turbomachinery Controls Conference 1995 are presented. Eleven papers were presented at the conference. A separate abstract was prepared for each of the nine papers for inclusion in the Energy Science and Technology Database.

  11. Special Conference on Tumor Immunology and Immunotherapy: A New Chapter.

    PubMed

    Byrne, Katelyn T; Vonderheide, Robert H; Jaffee, Elizabeth M; Armstrong, Todd D

    2015-05-12

    The overall objective of the fifth American Association for Cancer Research Special Conference, "Tumor Immunology and Immunotherapy: A New Chapter," organized by the Cancer Immunology Working Group, was to highlight multidisciplinary approaches of immunotherapy and mechanisms related to the ability of immunotherapy to fight established tumors. With the FDA approval of sipuleucel-T, ipilimumab (anti-CTLA-4; Bristol-Myers Squibb), and the two anti-PD-1 antibodies, pembrolizumab (formerly MK-3475 or lambrolizumab; Merck) and nivolumab (Bristol-Myers Squibb), immunotherapy has become a mainstream treatment option for some cancers. Many of the data presented at the conference and reviewed in this article showcase the progress made in determining the mechanistic reasons for the success of some treatments and the mechanisms associated with tolerance within the tumor microenvironment, both of which are potential targets for immunotherapy. In addition to combination and multimodal therapies, improvements in existing therapies will be needed to overcome the numerous ways that tumor-specific tolerance thwarts the immune system. This conference built upon the success of the 2012 conference and focused on seven progressing and/or emerging areas-new combination therapies, combination therapies and vaccine improvement, mechanisms of antibody therapy, factors in the tumor microenvironment affecting the immune response, the microbiomes effect on cancer and immunotherapy, metabolism in immunotherapy, and adoptive T-cell therapy. Cancer Immunol Res; 3(6); 1-8. ©2015 AACR.

  12. Special Conference on Tumor Immunology and Immunotherapy: A New Chapter

    PubMed Central

    Byrne, Katelyn T.; Vonderheide, Robert H.; Jaffee, Elizabeth M.; Armstrong, Todd D.

    2015-01-01

    The overall objective of the fifth American Association for Cancer Research Special Conference on “Tumor Immunology and Immunotherapy: A New Chapter” organized by the Cancer Immunology Working Group was to highlight multidisciplinary approaches of immunotherapy and mechanisms related to the ability of immunotherapy to fight established tumors. With the FDA approval of sipuleucel-T, ipilimumab (anti-CTLA4; Bristol-Myers Squibb [BMS]), and the two anti-PD-1 antibodies, pembrolizumab (formerly MK-3475 or lambrolizumab; Merck) and nivolumab (BMS), immunotherapy has become a mainstream treatment option for some cancer. Many of the data presented at the conference and reviewed in this article showcase the progress made in determining the mechanistic reasons for the success of some treatments and the mechanisms associated with tolerance within the tumor microenvironment, both of which are potential targets for immunotherapy. In addition to combination and multimodal therapies, improvements in existing therapies will be needed to overcome the numerous ways that tumor-specific tolerance thwarts the immune system. This conference built upon the success of the 2012 conference, and focused on seven progressing and/or emerging areas that include: New combination therapies; Combination therapies and vaccine Improvement; Mechanisms of antibody therapy; Factors in the tumor microenvironment affecting the immune response; The microbiomes effect on cancer and immunotherapy; Metabolism in immunotherapy; and Adoptive T-cell therapy. PMID:25968457

  13. Twitter use in physics conferences.

    PubMed

    Webb, Stephen

    An analysis of Twitter use in 116 conferences suggests that the service is used more extensively at PACS10 conferences (those devoted to the physics of elementary particles and fields) and PACS90 conferences (those devoted to geophysics, astronomy, and astrophysics) than at conferences in other fields of physics. Furthermore, Twitter is used in a qualitatively different manner. A possible reason for these differences is discussed.

  14. Conducting Telephone Conference IEPs

    ERIC Educational Resources Information Center

    Patterson, Philip Patrick; Petit, Constance; Williams, Shandelyn

    2007-01-01

    Synchronizing the availability of team members for Individual Education Plan (IEP) meetings can be a daunting task. Fortunately, the Individuals with Disabilities Education Improvement Act of 2004 permits alternative means of conducting such meetings. An example of an alternate means is a telephone conference, whereby parents communicate over the…

  15. REGIONAL CONFERENCE SUMMARIES, 1966.

    ERIC Educational Resources Information Center

    Bureau of Adult, Vocational, and Technical Education (DHEW/OE), Washington, DC. Div. of Vocational and Technical Education.

    AN AVERAGE OF 200 TEACHER EDUCATORS, STATE DIRECTORS, LAYMEN, AND REPRESENTATIVES OF VARIOUS AGENCIES ATTENDED EACH OF NINE REGIONAL CONFERENCES CONDUCTED THROUGHOUT THE UNITED STATES TO DISCUSS THE INFLUENCE OF SOCIAL AND ECONOMIC CHANGES AND PROBLEMS IN PLANNING AND CONDUCTING VOCATIONAL AND TECHNICAL EDUCATION PROGRAMS. MAJOR SPEECHES PRESENTED…

  16. Open Mind Conference

    NASA Technical Reports Server (NTRS)

    King, Alexander H.

    1995-01-01

    Open Mind, The Association for the achievement of diversity in higher education, met in conference in Albuquerque, New Mexico, between October 16 and 18, 1992. A number of workgroups met to discuss the goals, structure, and generally evaluate the Association and its achievements. A summary of the workgroup sessions and their minutes are included.

  17. The interparliamentary conference

    SciTech Connect

    Not Available

    1990-01-01

    The purpose of this conference was to provide a forum for exchange of information on environmental problems with global origins and consequences. The areas of major concern included the following: global climate change; deforestation and desertification; preservation of biological diversity; safeguarding oceans and water resources; population growth; destruction of the stratospheric ozone layer; and sustainable development.

  18. Press Conference - Skylab 3

    NASA Image and Video Library

    1972-08-14

    S72-46699 (19 Jan. 1972) --- Prime crew members of the scheduled second Skylab mission are introduced to the media during a press conference in January 1972 at the Manned Spacecraft Center (MSC). From left to right are astronauts Jack R. Lousma, pilot; Owen K. Garriott, science pilot, and Alan L. Bean, commander. Photo credit: NASA

  19. Creating Better Satellite Conferences.

    ERIC Educational Resources Information Center

    Horner, Tommy

    1998-01-01

    Presents four ways to improve broadcasts of company satellite conferences, including creative site selection (using facilities at educational institutions rather than hotel rooms); creative programming (using graphics and other interruptions to break up lectures or speeches); creative crew selection; and creative downlink site activities (to…

  20. Government Quality Conference Proceedings

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The Government Quality Conference was an attempt to bring together executive organizations and senior individuals in the Federal Government that have a desire to improve productivity. It was designed to provide an exchange of ideas based on experience, and to encourage individual management initiatives to tap the capabilities of Federal employees.

  1. Metabolic Engineering X Conference

    SciTech Connect

    Flach, Evan

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  2. STS-134 Press Conference

    NASA Image and Video Library

    2011-03-24

    JSC2011-E-028491 (24 March 2011) --- European Space Agency astronaut Roberto Vittori, STS-134 mission specialist, fields a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA or National Aeronautics and Space Administration

  3. STS-134 Press Conference

    NASA Image and Video Library

    2011-03-24

    JSC2011-E-028498 (24 March 2011) --- European Space Agency astronaut Roberto Vittori, STS-134 mission specialist, responds to a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA or National Aeronautics and Space Administration

  4. Expedition 34 Press Conference

    NASA Image and Video Library

    2012-12-18

    Russian backup crew member Fyodor Yurchikin, right, answers a reporter's question at a press conference held at the Cosmonaut Hotel, on Tuesday, Dec. 18, 2012, in Baikonur, Kazakhstan. Seen next to him are NASA backup crew member Karen Nyberg and Expedition 34/35 Canadian Space Agency astronaut Chris Hadfield. Photo Credit: (NASA/Carla Cioffi)

  5. STS-134 Press Conference

    NASA Image and Video Library

    2011-03-24

    JSC2011-E-028488 (24 March 2011) --- NASA astronaut Greg H. Johnson, STS-134 pilot, responds to a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA or National Aeronautics and Space Administration

  6. STS-134 Press Conference

    NASA Image and Video Library

    2011-03-24

    JSC2011-E-028490 (24 March 2011) --- NASA astronaut Michael Fincke, STS-134 mission specialist, responds to a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA or National Aeronautics and Space Administration

  7. STS-134 Press Conference

    NASA Image and Video Library

    2011-03-24

    JSC2011-E-028496 (24 March 2011) --- NASA astronaut Andrew Feustel, STS-134 mission specialist, responds to a question from a reporter during a preflight press conference at NASA's Johnson Space Center. Photo credit: NASA or National Aeronautics and Space Administration

  8. Microbicides 2006 conference

    PubMed Central

    Ramjee, Gita; Shattock, Robin; Delany, Sinead; McGowan, Ian; Morar, Neetha; Gottemoeller, Megan

    2006-01-01

    Current HIV/AIDS statistics show that women account for almost 60% of HIV infections in Sub-Saharan Africa. HIV prevention tools such as male and female condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are products designed to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition. The biannual Microbicides conference took place in Cape Town, South Africa from 23–26 April 2006. The conference was held for the first time on the African continent, the region worst affected by the HIV/AIDS pandemic. The conference brought together a record number of 1,300 scientists, researchers, policy makers, healthcare workers, communities and advocates. The conference provided an opportunity for an update on microbicide research and development as well as discussions around key issues such as ethics, acceptability, access and community involvement. This report discusses the current status of microbicide research and development, encompassing basic and clinical science, social and behavioural science, and community mobilisation and advocacy activities. PMID:17038196

  9. Effective Parent Conferences

    ERIC Educational Resources Information Center

    Elmore, Michael

    2008-01-01

    Conferences with an upset parent, teacher, or student should be opportunities for schools to build relationships with the community and to foster a positive school culture. But in reality, they are often held because a problem has arisen and often end with stakeholders having a less-than-positive image of the school. Understanding the steps that…

  10. Conference on Censorship.

    ERIC Educational Resources Information Center

    Meltzer, Milton; And Others

    In this collection of seven speeches from the University of Missouri Conference on Censorship, writers focus on the various aspects of censorship. Speeches are by (1) Milton Meltzer, who lauds those writers who were forced to battle with censors; (2) Enid Olson, who explores the censorship problems faced by teachers and school librarians; (3)…

  11. APPA 2011 Conference Highlights

    ERIC Educational Resources Information Center

    Facilities Manager, 2011

    2011-01-01

    This article presents highlights of APPA conference that was held on July 16-18, 2011. The highlights feature photos of 2011-2012 board of directors, outgoing senior regional representatives to the board, meritorious service award, APPA fellow, president's recognition and gavel exchange, and diamond business partner award.

  12. Expedition 28 Press Conference

    NASA Image and Video Library

    2011-06-06

    Expedition 28 NASA Flight Engineer Mike Fossum, left, and Soyuz Commander Sergei Volkov of Russia share a laugh during a press conference, Monday, June 6, 2011, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch on Tuesday, June 8, from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  13. Expedition 29 Press Conference

    NASA Image and Video Library

    2011-11-12

    Expedition 29 Soyuz Commander Anton Shkaplerov answers a reporter’s question during a press conference held at the Cosmonaut Hotel in Baikonur, Kazakhstan on Saturday, Nov. 12, 2011. The mission is set to launch November 14 from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  14. Expedition 28 Press Conference

    NASA Image and Video Library

    2011-06-06

    Expedition 28 NASA Flight Engineer Mike Fossum, speaks during a press conference, Monday, June 6, 2011, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch on Tuesday, June 8, from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  15. Expedition 28 Press Conference

    NASA Image and Video Library

    2011-06-06

    Expedition 28 NASA Flight Engineer Mike Fossum speaks during a press conference, Monday, June 6, 2011, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch on Tuesday, June 8, from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  16. Expedition 28 Press Conference

    NASA Image and Video Library

    2011-06-06

    Expedition 28 NASA Flight Engineer Mike Fossum, left, and Soyuz Commander Sergei Volkov of Russia are seen during a press conference, Monday, June 6, 2011, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch on Tuesday, June 8, from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  17. Expedition 29 Press Conference

    NASA Image and Video Library

    2011-11-12

    Expedition 29 backup crew members NASA Flight Engineer Joseph Acaba, far left, Russian Soyuz Commander Gennady Padalka, center, and Russian Flight Engineer Sergei Revin are seen at a press conference held at the Cosmonaut Hotel in Baikonur, Kazakhstan on Saturday, Nov. 12, 2011. Photo Credit: (NASA/Carla Cioffi)

  18. Expedition 29 Press Conference

    NASA Image and Video Library

    2011-11-12

    Expedition 29 NASA Flight Engineer Dan Burbank answers a reporter’s question during a press conference held at the Cosmonaut Hotel in Baikonur, Kazakhstan on Saturday, Nov. 12, 2011. The launch of the Soyuz spacecraft with Expedition 29 NASA Flight Engineer Dan Burbank, Soyuz Commander Anton Shkaplerov and Flight Engineer Anatoly Ivanishin is scheduled for November 14. Photo Credit: (NASA/Carla Cioffi)

  19. Expedition 28 Press Conference

    NASA Image and Video Library

    2011-06-06

    Expedition 28 NASA backup Flight Engineer Don Pettit looks on during a press conference, Monday, June 6, 2011, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch on Tuesday, June 8, from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  20. Expedition 28 Press Conference

    NASA Image and Video Library

    2011-06-06

    Expedition 28 Soyuz Commander Sergei Volkov of Russia speaks during a press conference, Monday, June 6, 2011, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch on Tuesday, June 7, from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  1. Expedition 29 Press Conference

    NASA Image and Video Library

    2011-11-12

    Expedition 29 NASA backup crew member Joe Acaba is seen at a press conference held at the Cosmonaut Hotel, Saturday, Nov. 12, 2011 at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch November 14 from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  2. Expedition 28 Press Conference

    NASA Image and Video Library

    2011-06-06

    NASA backup Flight Engineer Don Pettit speaks during a press conference, Monday, June 6, 2011, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch on Tuesday, June 8, from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  3. Expedition 28 Press Conference

    NASA Image and Video Library

    2011-06-06

    Expedition 28 Soyuz Commander Sergei Volkov speaks during a press conference, Monday, June 6, 2011, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch on Tuesday, June 8, from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  4. Expedition 39 Press Conference

    NASA Image and Video Library

    2014-03-24

    Expedition 39 flight engineer Steve Swanson of NASA is seen in quarantine, behind glass, during the final press conference be Monday, March 24, 2014, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission to the International Space Station is set to launch March 26 from the Baikonur Cosmodrome. Photo Credit: (NASA/Bill Ingalls)

  5. Expedition 28 Press Conference

    NASA Image and Video Library

    2011-06-06

    Russian backup Flight Engineer Oleg Kononenko speaks during a press conference, Monday, June 6, 2011, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch on Tuesday, June 8, from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  6. Expedition 29 Press Conference

    NASA Image and Video Library

    2011-11-12

    Expedition 29 backup crew members Joseph Acaba, left, and Russian Flight Engineer Gennady Padalka share a few words during a press conference held at the Cosmonaut Hotel in Baikonur, Kazakhstan on Saturday, Nov. 12, 2011. Photo Credit: (NASA/Carla Cioffi)

  7. Expedition 29 Press Conference

    NASA Image and Video Library

    2011-11-12

    Expedition 29 Flight Engineer Anatoly Ivanishin is seen at a press conference held at the Cosmonaut Hotel, Saturday, Nov. 12, 2011 at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch November 14 from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  8. Expedition 40 Press Conference

    NASA Image and Video Library

    2014-05-27

    A man taking a picture with a cell phone is seen reflected in the glass separating the quarantined crew during a press conference on Tuesday, May 27, 2014, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission to the International Space Station is set to launch May 29 from the Baikonur Cosmodrome. Photo Credit: (NASA/Joel Kowsky)

  9. Expedition 29 Press Conference

    NASA Image and Video Library

    2011-11-12

    Expedition 29 Russian Flight Engineer Anatoly Ivanishin answers a reporter’s question during a press conference held at the Cosmonaut Hotel in Baikonur, Kazakhstan on Saturday, Nov. 12, 2011. The launch of the Soyuz spacecraft with Ivanishin, Soyuz Commander Anton Shkaplerov and NASA Flight Engineer Dan Burbank is scheduled for November 14. Photo Credit: (NASA/Carla Cioffi)

  10. Expedition 28 Press Conference

    NASA Image and Video Library

    2011-06-06

    Expedition 28 NASA Flight Engineer Mike Fossum, left, looks on as Soyuz Commander Sergei Volkov speaks during a press conference, Monday, June 6, 2011, at the Cosmonaut Hotel in Baikonur, Kazakhstan. The mission is set to launch on Tuesday, June 8, from the Baikonur Cosmodrome. Photo Credit: (NASA/Carla Cioffi)

  11. Expedition 41 Press Conference

    NASA Image and Video Library

    2014-09-24

    NASA Expedition 41 backup crew member Flight Engineer Mikhail Kornienko of the Russian Federal Space Agency (Roscosmos) answers a question during a press conference Wednesday, Sept. 24, 2014 at the Cosmonaut Hotel in Baikonur, Kazakhstan. The prime crew is set to launch Sept. 26 from the Baikonur Cosmodrome. Photo Credit: (NASA/Aubrey Gemignani)

  12. Annual Conference Abstracts

    ERIC Educational Resources Information Center

    Journal of Engineering Education, 1972

    1972-01-01

    Includes abstracts of papers presented at the 80th Annual Conference of the American Society for Engineering Education. The broad areas include aerospace, affiliate and associate member council, agricultural engineering, biomedical engineering, continuing engineering studies, chemical engineering, civil engineering, computers, cooperative…

  13. Conference summary - Personal views

    NASA Astrophysics Data System (ADS)

    Lub, J.

    2016-05-01

    This is a collection of remarks on the three and a half days of the RR Lyrae 2015 Conference, limited only by my own lack of attention and understanding. I end with some personal recollections on my complete failure, even though doing the necessary calculations, to spot the importance and the possible application of Fourier amplitudes and phases of the RR Lyrae light curves.

  14. Grammar! A Conference Report.

    ERIC Educational Resources Information Center

    King, Lid, Ed.; Boaks, Peter, Ed.

    Papers from a conference on the teaching of grammar, particularly in second language instruction, include: "Grammar: Acquisition and Use" (Richard Johnstone); "Grammar and Communication" (Brian Page); "Linguistic Progression and Increasing Independence" (Bernardette Holmes); "La grammaire? C'est du bricolage!" ("Grammar? That's Hardware!") (Barry…

  15. 2008 Combat Vehicles Conference

    DTIC Science & Technology

    2008-10-22

    General Michael M. Brogan Combat Vehicles Conference Marine Corps Systems Command 21 October 2008 2 MCSC •LAV •AAV •Tank •HMMWV/ ECV •MRAP PEO LS...34,226 Total 56,649 1985 IOC 1996 M1114 armored HMMWV Limited Production 2006 M1100 series begins fielding scalable armor 2009-10 ECV II

  16. Annual Conference Abstracts

    ERIC Educational Resources Information Center

    Journal of Engineering Education, 1972

    1972-01-01

    Includes abstracts of papers presented at the 80th Annual Conference of the American Society for Engineering Education. The broad areas include aerospace, affiliate and associate member council, agricultural engineering, biomedical engineering, continuing engineering studies, chemical engineering, civil engineering, computers, cooperative…

  17. Expedition 6 Press Conference

    NASA Image and Video Library

    2003-05-05

    Expedition 6 Flight Engineer Nikolai Budarin, left, Commander Ken Bowersox and International Space Station Science Officer Don Pettit, right, pose for photos at a press conference at the Gagarin Cosmonaut Training Center in Star City, Russia, Thursday, May 6, 2003. Photo Credit: (NASA/Bill Ingalls)

  18. Expedition 6 Press Conference

    NASA Image and Video Library

    2003-05-05

    Expedition 6 Flight Engineer Nikolai Budarin, left, Commander Ken Bowersox and NASA International Space Station Science Officer Don Pettit, right, answer questions during a press conference at the Gagarin Cosmonaut Training Center in Star City, Russia, Thursday, May 6, 2003. Photo Credit: (NASA/Bill Ingalls)

  19. Constellation Program Press Conference

    NASA Image and Video Library

    2006-06-04

    NASA Administrator Michael Griffin, left, Scott Horowitz, NASA Associate Administrator for Exploration Systems and Jeff Hanley, Constellation Program Manager, right, are seen during a press conference outlining specific center responsibilities associated with the Constellation Program for robotic and human Moon and Mars exploration, Monday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit (NASA/Bill Ingalls)

  20. Constellation Program Press Conference

    NASA Image and Video Library

    2006-06-04

    Scott Horowitz, NASA Associate Administrator for Exploration Systems, center, speaks as Jeff Hanley, Constellation Program Manager, right, looks on during a press conference outlining specific center responsibilities associated with the Constellation Program for robotic and human Moon and Mars exploration, Monday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit (NASA/Bill Ingalls)

  1. Hydrogen Conference: Workshop Proceedings

    SciTech Connect

    1989-10-01

    Hydrogen is currently a major chemical/fuel with long-term energy system benefits that may impact the industry's physical and economic well-being. EPRI's recent hydrogen conference concluded that to be competitive, the production cost must take into account environmental and end-use efficiency benefits.

  2. Google Moon Press Conference

    NASA Image and Video Library

    2009-07-19

    Andrew Chaikin, author of "A Man on the Moon" speaks during a press conference, Monday, July 20, 2009, announcing the launch of Moon in Google Earth, an immersive 3D atlas of the Moon, accessible within Google Earth 5.0, Monday, July 20, 2009, at the Newseum in Washington. Photo Credit: (NASA/Bill Ingalls)

  3. Google Moon Press Conference

    NASA Image and Video Library

    2009-07-19

    Buzz Aldrin, the second man to walk on the moon, speaks during a press conference, Monday, July 20, 2009, announcing the launch of Moon in Google Earth, an immersive 3D atlas of the Moon, accessible within Google Earth 5.0, Monday, July 20, 2009, at the Newseum in Washington. Photo Credit: (NASA/Bill Ingalls)

  4. Google Moon Press Conference

    NASA Image and Video Library

    2009-07-19

    Apollo 11 astronaut Buzz Aldrin, the second man to walk on the Moon, speaks during a press conference, Monday, July 20, 2009, announcing the launch of Moon in Google Earth, an immersive 3D atlas of the Moon, accessible within Google Earth 5.0, Monday, July 20, 2009, at the Newseum in Washington. Photo Credit: (NASA/Bill Ingalls)

  5. Google Moon Press Conference

    NASA Image and Video Library

    2009-07-19

    NASA Deputy Administrator Lori Garver, speaks during a press conference, Monday, July 20, 2009, announcing the launch of Moon in Google Earth, an immersive 3D atlas of the Moon, accessible within Google Earth 5.0, Monday, July 20, 2009, at the Newseum in Washington. Photo Credit: (NASA/Bill Ingalls)

  6. Google Moon Press Conference

    NASA Image and Video Library

    2009-07-19

    Tiffany Montague, Technical Program Manager for NASA and Google Lunar X PRIZE, Google, Inc., speaks during a press conference, Monday, July 20, 2009, announcing the launch of Moon in Google Earth, an immersive 3D atlas of the Moon, accessible within Google Earth 5.0, Monday, July 20, 2009, at the Newseum in Washington. Photo Credit: (NASA/Bill Ingalls)

  7. Google Moon Press Conference

    NASA Image and Video Library

    2009-07-19

    Brian McLendon, VP of Engineering, Google, Inc., speaks during a press conference, Monday, July 20, 2009, announcing the launch of Moon in Google Earth, an immersive 3D atlas of the Moon, accessible within Google Earth 5.0, Monday, July 20, 2009, at the Newseum in Washington. Photo Credit: (NASA/Bill Ingalls)

  8. Google Moon Press Conference

    NASA Image and Video Library

    2009-07-19

    Yoshinori Yoshimura, a respresentative from the Japan Aerospace Exploration Agency (JAXA), speaks during a press conference, Monday, July 20, 2009, announcing the launch of Moon in Google Earth, an immersive 3D atlas of the Moon, accessible within Google Earth 5.0, Monday, July 20, 2009, at the Newseum in Washington. Photo Credit: (NASA/Bill Ingalls)

  9. Google Moon Press Conference

    NASA Image and Video Library

    2009-07-19

    Michael Weiss-Malik, Product Manager for Moon in Google Earth, Google, Inc., speaks during a press conference, Monday, July 20, 2009, announcing the launch of Moon in Google Earth, an immersive 3D atlas of the Moon, accessible within Google Earth 5.0, Monday, July 20, 2009, at the Newseum in Washington. Photo Credit: (NASA/Bill Ingalls)

  10. Google Moon Press Conference

    NASA Image and Video Library

    2009-07-19

    Miles O'Brien, former chief science and tech correspondent for CNN, speaks during a press conference, Monday, July 20, 2009, announcing the launch of Moon in Google Earth, an immersive 3D atlas of the Moon, accessible within Google Earth 5.0, Monday, July 20, 2009, at the Newseum in Washington. Photo Credit: (NASA/Bill Ingalls)

  11. Conference presentations with confidence.

    PubMed

    Strickland, T

    1999-01-01

    Remember that great presentation you heard at last year's convention? Perhaps the marketing case study was especially interesting. Or perhaps you wondered whether you could use the organizational tools the speaker described in your own work. Finally, you might have wondered, "Could I offer a conference presentation at some point?" The answer: yes!

  12. 2002 NASPSA Conference Abstracts.

    ERIC Educational Resources Information Center

    Journal of Sport & Exercise Psychology, 2002

    2002-01-01

    Contains abstracts from the 2002 conference of the North American Society for the Psychology of Sport and Physical Activity. The publication is divided into three sections: the preconference workshop, "Effective Teaching Methods in the Classroom;" symposia (motor development, motor learning and control, and sport psychology); and free…

  13. Annual Conference Abstracts

    ERIC Educational Resources Information Center

    Engineering Education, 1976

    1976-01-01

    Presents the abstracts of 158 papers presented at the American Society for Engineering Education's annual conference at Knoxville, Tennessee, June 14-17, 1976. Included are engineering topics covering education, aerospace, agriculture, biomedicine, chemistry, computers, electricity, acoustics, environment, mechanics, and women. (SL)

  14. 2002 NASPSA Conference Abstracts.

    ERIC Educational Resources Information Center

    Journal of Sport & Exercise Psychology, 2002

    2002-01-01

    Contains abstracts from the 2002 conference of the North American Society for the Psychology of Sport and Physical Activity. The publication is divided into three sections: the preconference workshop, "Effective Teaching Methods in the Classroom;" symposia (motor development, motor learning and control, and sport psychology); and free…

  15. Expedition 52 Press Conference

    NASA Image and Video Library

    2017-07-10

    Expedition 52 flight engineers Paolo Nespoli of ESA, left, Sergey Ryazanskiy of Roscosmos, center, and Expedition 52 flight engineer Randy Bresnik of NASA pose for group photograph at the conclusion of their crew press conference at the Gagarin Cosmonaut Training Center (GCTC), Monday, July 10, 2017 in Star City, Russia. Photo Credit: (NASA/Bill Ingalls)

  16. Expedition 50 Press Conference

    NASA Image and Video Library

    2016-10-26

    Expedition 50 NASA astronaut Peggy Whitson, left, Russian cosmonaut Oleg Novitskiy of Roscosmos, center, and ESA astronaut Thomas Pesquet pose for a group photograph at the conclusion of a press conference, Wednesday, Oct. 26, 2016, at the Gagarin Cosmonaut Training Center (GCTC) in Star City, Russia. Photo Credit: (NASA/Bill Ingalls)

  17. Expedition 52 Press Conference

    NASA Image and Video Library

    2017-07-10

    A painting of Yuri Gagarin is seen in the lobby of the building where the Expedition 52 prime and backup crews held a crew press conference on the grounds of the Gagarin Cosmonaut Training Center (GCTC), Monday, July 10, 2017 in Star City, Russia. Photo Credit: (NASA/Bill Ingalls)

  18. DEVELOP students attend conference

    NASA Technical Reports Server (NTRS)

    2009-01-01

    Last month, Madeline Brozen and Jason Jones of the DEVELOP Program at John C. Stennis Space Center joined members from the program's national office at Langley Research Center to attend the Southern Growth Policies Board annual conference in Biloxi. Pictured are (l to r): Karen Allsbrook, Jonathan Gleason, Gov. Haley Barbour, Madeline Brozen, Lindsay Rogers and Tracey Silcox.

  19. Constellation Program Press Conference

    NASA Image and Video Library

    2006-06-04

    Jeff Hanley, Constellation Program Manager, speaks during a press conference outlining specific center responsibilities associated with the Constellation Program for robotic and human Moon and Mars exploration, Monday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit (NASA/Bill Ingalls)

  20. Constellation Program Press Conference

    NASA Image and Video Library

    2006-06-04

    Dean Acosta, NASA Deputy Assistant Administrator and Press Secretary, moderates a press conference with NASA Administrator Michael Griffin Scott Horowitz, NASA Associate Administrator for Exploration Systems and Jeff Hanley, Constellation Program Manager, outlining specific center responsibilities associated with the Constellation Program for robotic and human Moon and Mars exploration, Monday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit (NASA/Bill Ingalls)

  1. Constellation Program Press Conference

    NASA Image and Video Library

    2006-06-04

    Scott Horowitz, NASA Associate Administrator for Exploration Systems, left, looks on as Jeff Hanley, Constellation Program Manager, speaks during a press conference outlining specific center responsibilities associated with the Constellation Program for robotic and human Moon and Mars exploration, Monday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit (NASA/Bill Ingalls)

  2. Constellation Program Press Conference

    NASA Image and Video Library

    2006-06-04

    NASA Administrator Michael Griffin, left, looks on as Scott Horowitz, NASA Associate Administrator for Exploration Systems speaks during a press conference outlining specific center responsibilities associated with the Constellation Program for robotic and human Moon and Mars exploration, Monday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit (NASA/Bill Ingalls)

  3. Constellation Program Press Conference

    NASA Image and Video Library

    2006-06-04

    Members of the media listen during a press conference with NASA Administrator Michael Griffin, Scott Horowitz, NASA Associate Administrator for Exploration Systems and Jeff Hanley, Constellation Program Manager, outlining specific center responsibilities associated with the Constellation Program for robotic and human Moon and Mars exploration, Monday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit (NASA/Bill Ingalls)

  4. Constellation Program Press Conference

    NASA Image and Video Library

    2006-06-04

    NASA Administrator Michael Griffin, speaks during a press conference outlining specific center responsibilities associated with the Constellation Program for robotic and human Moon and Mars exploration, Monday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit (NASA/Bill Ingalls)

  5. Constellation Program Press Conference

    NASA Image and Video Library

    2006-06-04

    Scott Horowitz, NASA Associate Administrator for Exploration Systems, left, and Jeff Hanley, Constellation Program Manager, are seen during a press conference outlining specific center responsibilities associated with the Constellation Program for robotic and human Moon and Mars exploration, Monday, June 5, 2006, at NASA Headquarters in Washington. Photo Credit (NASA/Bill Ingalls)

  6. Conference on Navajo Orthography.

    ERIC Educational Resources Information Center

    Ohannessian, Sirarpi; And Others

    This report on the Conference on Navajo Orthography, held in Albuquerque, New Mexico on May 2-3, 1969 constitutes a summary of the discussion and decisions of a meeting which was convened by the Center for Applied Linguistics under contract with the Bureau of Indian Affairs to agree on an orthography for the Navajo language. The immediate purpose…

  7. Conference Abstracts: AEDS '84.

    ERIC Educational Resources Information Center

    Baird, William E.

    1985-01-01

    The Association of Educational Data Systems (AEDS) conference included 102 presentations. Abstracts of seven of these presentations are provided. Topic areas considered include LOGO, teaching probability through a computer game, writing effective computer assisted instructional materials, computer literacy, research on instructional…

  8. Effective Parent Conferences

    ERIC Educational Resources Information Center

    Elmore, Michael

    2008-01-01

    Conferences with an upset parent, teacher, or student should be opportunities for schools to build relationships with the community and to foster a positive school culture. But in reality, they are often held because a problem has arisen and often end with stakeholders having a less-than-positive image of the school. Understanding the steps that…

  9. A Conference of Hope.

    ERIC Educational Resources Information Center

    American Printing House for the Blind, Louisville, KY. Dept. of Educational Research.

    Presented are the proceedings of the First Historic Helen Keller World Conference on Services to Deaf-Blind Youths and Adults, held in New York City in September, 1977 on the theme "The Deaf-Blind Person in the Community." Reports have the following titles and authors: "Definition, Demography, Causes and Prevention of Deaf-Blindness; Finding and…

  10. Google Moon Press Conference

    NASA Image and Video Library

    2009-07-19

    Alan Eustace, Senior VP of Engineering and Research, Google, Inc., speaks during a press conference, Monday, July 20, 2009, announcing the launch of Moon in Google Earth, an immersive 3D atlas of the Moon, accessible within Google Earth 5.0, Monday, July 20, 2009, at the Newseum in Washington. Photo Credit: (NASA/Bill Ingalls)

  11. DEVELOP students attend conference

    NASA Image and Video Library

    2009-06-08

    Last month, Madeline Brozen and Jason Jones of the DEVELOP Program at John C. Stennis Space Center joined members from the program's national office at Langley Research Center to attend the Southern Growth Policies Board annual conference in Biloxi. Pictured are (l to r): Karen Allsbrook, Jonathan Gleason, Gov. Haley Barbour, Madeline Brozen, Lindsay Rogers and Tracey Silcox.

  12. A Conference of Hope.

    ERIC Educational Resources Information Center

    American Printing House for the Blind, Louisville, KY. Dept. of Educational Research.

    Presented are the proceedings of the First Historic Helen Keller World Conference on Services to Deaf-Blind Youths and Adults, held in New York City in September, 1977 on the theme "The Deaf-Blind Person in the Community." Reports have the following titles and authors: "Definition, Demography, Causes and Prevention of Deaf-Blindness; Finding and…

  13. Base specific binding of deoxyguanylate and deoxycytidylate antibodies to double stranded DNA.

    PubMed Central

    Jacob, A; Jacob, T M

    1982-01-01

    Antibodies raised in rabbits against deoxyguanylate and deoxycytidylate bind to 3H-lambda double stranded DNA and the binding is base specific. The concentrations of antibody populations that bind to double stranded DNA are much less than those binding to denatured DNA. Due to their low concentrations, these antibodies were not detected in earlier studies. These antibodies are expected to be useful to probe the conformational flexibilities of double stranded DNAs. PMID:6217448

  14. Expression of recombinant antibodies.

    PubMed

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with "human-like" post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

  15. Recombinant renewable polyclonal antibodies.

    PubMed

    Ferrara, Fortunato; D'Angelo, Sara; Gaiotto, Tiziano; Naranjo, Leslie; Tian, Hongzhao; Gräslund, Susanne; Dobrovetsky, Elena; Hraber, Peter; Lund-Johansen, Fridtjof; Saragozza, Silvia; Sblattero, Daniele; Kiss, Csaba; Bradbury, Andrew R M

    2015-01-01

    Only a small fraction of the antibodies in a traditional polyclonal antibody mixture recognize the target of interest, frequently resulting in undesirable polyreactivity. Here, we show that high-quality recombinant polyclonals, in which hundreds of different antibodies are all directed toward a target of interest, can be easily generated in vitro by combining phage and yeast display. We show that, unlike traditional polyclonals, which are limited resources, recombinant polyclonal antibodies can be amplified over one hundred million-fold without losing representation or functionality. Our protocol was tested on 9 different targets to demonstrate how the strategy allows the selective amplification of antibodies directed toward desirable target specific epitopes, such as those found in one protein but not a closely related one, and the elimination of antibodies recognizing common epitopes, without significant loss of diversity. These recombinant renewable polyclonal antibodies are usable in different assays, and can be generated in high throughput. This approach could potentially be used to develop highly specific recombinant renewable antibodies against all human gene products.

  16. Recombinant renewable polyclonal antibodies

    PubMed Central

    Ferrara, Fortunato; D’Angelo, Sara; Gaiotto, Tiziano; Naranjo, Leslie; Tian, Hongzhao; Gräslund, Susanne; Dobrovetsky, Elena; Hraber, Peter; Lund-Johansen, Fridtjof; Saragozza, Silvia; Sblattero, Daniele; Kiss, Csaba; Bradbury, Andrew RM

    2015-01-01

    Only a small fraction of the antibodies in a traditional polyclonal antibody mixture recognize the target of interest, frequently resulting in undesirable polyreactivity. Here, we show that high-quality recombinant polyclonals, in which hundreds of different antibodies are all directed toward a target of interest, can be easily generated in vitro by combining phage and yeast display. We show that, unlike traditional polyclonals, which are limited resources, recombinant polyclonal antibodies can be amplified over one hundred million-fold without losing representation or functionality. Our protocol was tested on 9 different targets to demonstrate how the strategy allows the selective amplification of antibodies directed toward desirable target specific epitopes, such as those found in one protein but not a closely related one, and the elimination of antibodies recognizing common epitopes, without significant loss of diversity. These recombinant renewable polyclonal antibodies are usable in different assays, and can be generated in high throughput. This approach could potentially be used to develop highly specific recombinant renewable antibodies against all human gene products. PMID:25530082

  17. Therapeutic Recombinant Monoclonal Antibodies

    ERIC Educational Resources Information Center

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  18. Production Of Human Antibodies

    NASA Technical Reports Server (NTRS)

    Sammons, David W.; Neil, Garry A.

    1993-01-01

    Process for making human monoclonal antibodies based on combination of techniques. Antibodies made active against specific antigen. Process involves in vivo immunization of human B lymphocyte cells in mice. B cells of interest enriched in vitro before fusion. Method potentially applicable to any antigen. Does not rely on use of Epstein-Barr virus at any step. Human lymphocytes taken from any source.

  19. Affinity purification of antibodies

    USDA-ARS?s Scientific Manuscript database

    Antibodies are provided in a variety of formats that includes antiserum, hybridoma culture supernatant or ascites. They can all be used successfully in crude form for the detection of target antigens by immunoassay. However, it is advantageous to use purified antibody in defined quantity to facil...

  20. Production Of Human Antibodies

    NASA Technical Reports Server (NTRS)

    Sammons, David W.; Neil, Garry A.

    1993-01-01

    Process for making human monoclonal antibodies based on combination of techniques. Antibodies made active against specific antigen. Process involves in vivo immunization of human B lymphocyte cells in mice. B cells of interest enriched in vitro before fusion. Method potentially applicable to any antigen. Does not rely on use of Epstein-Barr virus at any step. Human lymphocytes taken from any source.

  1. Expression of Recombinant Antibodies

    PubMed Central

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications. PMID:23908655

  2. Therapeutic Recombinant Monoclonal Antibodies

    ERIC Educational Resources Information Center

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  3. ALA Conference 2009: Chicago Hope

    ERIC Educational Resources Information Center

    Berry, John N., III

    2009-01-01

    There is joy among those who have the funds to go to Chicago for the American Library Association (ALA) annual conference, July 9-15. Every librarian knows there is nothing better than a Chicago gathering, with the city's wonderful haunts, museums, restaurants, and fine memories of past conferences. The conference program covers nearly every…

  4. Making Connections: Attending Professional Conferences

    ERIC Educational Resources Information Center

    Cherrstrom, Catherine A.

    2012-01-01

    Attending a professional conference is an effective way to explore and advance knowledge, skills, and careers. For graduate students, attending a conference is an effective way to explore academic fields and new professions. However, attending a professional conference requires precious resources--time and money--so the decision to attend, or not,…

  5. ALA Conference 2009: Chicago Hope

    ERIC Educational Resources Information Center

    Berry, John N., III

    2009-01-01

    There is joy among those who have the funds to go to Chicago for the American Library Association (ALA) annual conference, July 9-15. Every librarian knows there is nothing better than a Chicago gathering, with the city's wonderful haunts, museums, restaurants, and fine memories of past conferences. The conference program covers nearly every…

  6. Summary: A Very Timely Conference

    NASA Astrophysics Data System (ADS)

    Wyse, Rosemary F. G.

    2012-04-01

    The conference poster includes a very apt phrase that describes a primary motivation for this conference: Time discovers truth. This aphorism, attributed to Seneca, was certainly affirmed by the many exciting talks and discussions at this conference, in both formal and informal settings.

  7. Antiidiotypic antibodies to sperm in sera of fertile women that neutralize antisperm antibodies.

    PubMed Central

    Naz, R K; Ahmad, K; Menge, A C

    1993-01-01

    The presence of antiidiotypic antibodies (ab-2) to sperm was investigated in the sera of fertile, infertile, and virgin women using sperm-specific anti-FA-1 monoclonal antibody Fab'.ab-2 were detected in 71% (17/24) of sera from fertile women and in none (0/12) of the sera from virgin females by the enzyme-linked immunosorbent assay, Western blot procedure, and immunoprecipitation procedure. Sera from infertile women that had antisperm antibodies showed a minimal presence of ab-2, with only three sera (13%, 3/23) demonstrating the presence of low levels of ab-2. The ab-2 present in fertile women were capable of neutralizing the fertilization-inhibitory activity of anti-FA-1 antibody in a concentration-dependent manner in a human sperm penetration assay (SPA) of zona-free hamster oocytes. ab-2 were also capable of inhibiting the binding of antisperm antibodies to the sperm surface as determined by the immunobead binding technique. This is the first report demonstrating the presence of ab-2 in the sera of fertile women that are capable of neutralizing antisperm antibodies present in sera of infertile women. These findings suggest that the inability to detect antisperm antibody activity in the sera of fertile women may be due to higher levels of ab-2 present in these sera than levels found in sera of infertile women, although both groups may be producing antisperm antibody response after sexual exposure to sperm. Images PMID:8227348

  8. Antibodies for biodefense

    PubMed Central

    Froude, Jeffrey W; Stiles, Bradley; Pelat, Thibaut

    2011-01-01

    Potential bioweapons are biological agents (bacteria, viruses and toxins) at risk of intentional dissemination. Biodefense, defined as development of therapeutics and vaccines against these agents, has seen an increase, particularly in the US, following the 2001 anthrax attack. This review focuses on recombinant antibodies and polyclonal antibodies for biodefense that have been accepted for clinical use. These antibodies aim to protect against primary potential bioweapons or category A agents as defined by the Centers for Disease Control and Prevention (Bacillus anthracis, Yersinia pestis, Francisella tularensis, botulinum neurotoxins, smallpox virus and certain others causing viral hemorrhagic fevers) and certain category B agents. Potential for prophylactic use is presented, as well as frequent use of oligoclonal antibodies or synergistic effect with other molecules. Capacities and limitations of antibodies for use in biodefense are discussed, and are generally applicable to the field of infectious diseases. PMID:22123065

  9. Anti-insulin antibody test

    MedlinePlus

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  10. Selection of Recombinant Human Antibodies.

    PubMed

    Tomszak, Florian; Weber, Susanne; Zantow, Jonas; Schirrmann, Thomas; Hust, Michael; Frenzel, André

    2016-01-01

    Since the development of therapeutic antibodies the demand of recombinant human antibodies is steadily increasing. Traditionally, therapeutic antibodies were generated by immunization of rat or mice, the generation of hybridoma clones, cloning of the antibody genes and subsequent humanization and engineering of the lead candidates. In the last few years, techniques were developed that use transgenic animals with a human antibody gene repertoire. Here, modern recombinant DNA technologies can be combined with well established immunization and hybridoma technologies to generate already affinity maturated human antibodies. An alternative are in vitro technologies which enabled the generation of fully human antibodies from antibody gene libraries that even exceed the human antibody repertoire. Specific antibodies can be isolated from these libraries in a very short time and therefore reduce the development time of an antibody drug at a very early stage.In this review, we describe different technologies that are currently used for the in vitro and in vivo generation of human antibodies.

  11. Red Blood Cell Antibody Identification

    MedlinePlus

    ... name: Red Blood Cell Antibody Identification Related tests: Direct Antiglobulin Test ; RBC Antibody Screen ; Blood Typing ; Type ... a positive RBC antibody screen or a positive direct antiglobulin test (DAT) . It is used to identify ...

  12. Vector-mediated antibody gene transfer for infectious diseases.

    PubMed

    Schnepp, Bruce C; Johnson, Philip R

    2015-01-01

    This chapter discusses the emerging field of vector-mediated antibody gene transfer as an alternative vaccine for infectious disease, with a specific focus on HIV. However, this methodology need not be confined to HIV-1; the general strategy of vector-mediated antibody gene transfer can be applied to other difficult vaccine targets like hepatitis C virus, malaria, respiratory syncytial virus, and tuberculosis. This approach is an improvement over classical passive immunization strategies that administer antibody proteins to the host to provide protection from infection. With vector-mediated gene transfer, the antibody gene is delivered to the host, via a recombinant adeno-associated virus (rAAV) vector; this in turn results in long-term endogenous antibody expression from the injected muscle that confers protective immunity. Vector-mediated antibody gene transfer can rapidly move existing, potent broadly cross-neutralizing HIV-1-specific antibodies into the clinic. The gene transfer products demonstrate a potency and breadth identical to the original product. This strategy eliminates the need for immunogen design and interaction with the adaptive immune system to generate protection, a strategy that so far has shown limited promise.

  13. NIH Consensus Conference. Acupuncture.

    PubMed

    1998-11-04

    To provide clinicians, patients, and the general public with a responsible assessment of the use and effectiveness of acupuncture to treat a variety of conditions. A nonfederal, nonadvocate, 12-member panel representing the fields of acupuncture, pain, psychology, psychiatry, physical medicine and rehabilitation, drug abuse, family practice, internal medicine, health policy, epidemiology, statistics, physiology, biophysics, and the representatives of the public. In addition, 25 experts from these same fields presented data to the panel and a conference audience of 1200. Presentations and discussions were divided into 3 phases over 2 1/2 days: (1) presentations by investigators working in areas relevant to the consensus questions during a 2-day public session; (2) questions and statements from conference attendees during open discussion periods that were part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of the third. The conference was organized and supported by the Office of Alternative Medicine and the Office of Medical Applications of Research, National Institutes of Health, Bethesda, Md. The literature, produced from January 1970 to October 1997, was searched through MEDLINE, Allied and Alternative Medicine, EMBASE, and MANTIS, as well as through a hand search of 9 journals that were not indexed by the National Library of Medicine. An extensive bibliography of 2302 references was provided to the panel and the conference audience. Expert speakers prepared abstracts of their own conference presentations with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in the open forum and scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience

  14. Comparison of three tissue fixatives on the immunoreactivity of mammalian P-glycoprotein antibodies to teleost tissues

    SciTech Connect

    Hemmer, M.J. |; Courtney, L.A.; Benson, W.H.

    1994-12-31

    Mammalian P-glycoprotein is a highly conserved integral membrane protein functioning as an energy dependent plasma membrane efflux pump which decreases the concentration of certain lipophilic aromatic compounds entering the cell by diffusion. Studies indicate that P-glycoprotein is capable of increased expression in response to certain chemical stressors and has demonstrated the ability to transport xenobiotic contaminants. Expression of a xenobiotic transporter in teleost species could play a significant role in conferring resistance to fish populations exposed to xenobiotic stressors and may serve as a potential indicator of species at risk to environmental contaminants. Past studies demonstrated a strong correlation between corresponding mammalian and teleost tissues showing immunoreactivity to specific mammalian P-glycoprotein antibodies. In this study, comparisons of staining pattern, intensity, and tissue specificity between Lillie`s, Bouin`s and Dietrich`s fixed tissues was determined in the sheepshead minnow, Cyprinodon variegatus, using monoclonal antibodies (mAbs) C219, C494 and JSB-1. Immunoreactivity of the mAbs was found to be fixative-dependent and results are presented illustrating the differential staining patterns and tissue specificity observed for each tissue, fixative, and antibody combination. These data indicate tissue fixation has a significant impact on P-glycoprotein immunoreactivity in teleost tissues and must be considered in the comparison and interpretation of results.

  15. Duration of protective antibodies and correlation with survival in Nile tilapia Oreochromis niloticus following Streptococcus agalactiae vaccination.

    PubMed

    Pasnik, David J; Evans, Joyce J; Klesius, Phillip H

    2005-09-05

    Streptococcus agalactiae is a major piscine pathogen that causes significant morbidity and mortality among numerous species of freshwater, estuarine and marine fishes. Considering the economic importance of fishes susceptible to S. agalactiae throughout the world, an efficacious S. agalactiae vaccine was developed using an extracellular product (ECP) fraction and formalin-killed whole cells of S. agalactiae. A vaccine study was conducted by intraperitoneal (i.p.) injection in Nile tilapia Oreochromis niloticus in order to determine the duration of protection and its correlation to antibodies specific for this pathogen. After 47, 90 or 180 d post-vaccination (DPV), the fish were i.p. challenged with approximately 2.0 x 10(4) S. agalactiae colony-forming units (CFU) fish(-1) to determine the duration of protective immunity. The percent survival in control fish i.p.-injected with sterile TSB was 16,16, and 4% on 47, 90 and 180 DPV, respectively, while the percent survival for the vaccinated fish was 67, 62 and 49%, respectively. The specific mean antibody concentration of the vaccinated fish was significantly higher than that of the control fish, with significant correlation between the ELISA optical density (OD) and protection. These results indicate that the specific antibody has a correlation with protection following immunization with the S. agalactiae vaccine and that the vaccine can confer protection against S. agalactiae up to 180 DPV.

  16. Antiangiogenic antibody improves melanoma detection by fluorescently labeled therapeutic antibodies.

    PubMed

    Sweeny, Larissa; Prince, Andrew; Patel, Neel; Moore, Lindsay S; Rosenthal, Eben L; Hughley, Brian B; Warram, Jason M

    2016-12-01

    Evaluate if vascular normalization with an antiangiogenic monoclonal antibody improves detection of melanoma using fluorescently labeled antibody-based imaging. Preclinical. Panitumumab and control IgG were covalently linked to a near-infrared fluorescent probe (IRDye800CW). Immunodeficient mice with ear xenografts of melanoma cell lines (A375 and SKMEL5) were systemically injected (200 μg, tail vein) with either IgG-IRDye800CW, panitumumab-IRDye800CW, or a combination (bevacizumab [5mg/kg], administered 72 hours prepanitumumab-IRDye800CW) (n = 5). Primary tumors were imaged with open-field (LUNA, Novadaq, Toronto, Ontario, Canada) and closed-field (Pearl, LI-COR Biosciences, Lincoln, NB) imaging devices. Postresection, the concentration of labeled antibody within the tumor (μg/g) was calculated using normalized standards. The mean fluorescence within the melanoma tumors was greater for the combination group compared to panitumumab alone for both cell lines (P < 0.001). The tumor-to-background ratio (TBR) for the A375 tumors was greater for the combination (3.4-7.1) compared to the panitumumab alone (3.2-5.0) (P = 0.04). The TBR for SKMEL5 tumors was greater for the combination (2.4-6.0) compared to the panitumumab alone (2.2-3.9) (P = 0.02). Within A375 tumors, the concentration was lower for panitumumab (0.51 μg/g) compared to combination group (0.68 μg/g) (P = 0.036). Within SKMEL5 tumors, the concentration was lower for panitumumab (0.0.17 μg/g) compared to combination group (0.35 μg/g) (P = 0.048). Residual tumor (1.0-0.2 mg) could be differentiated from background in both panitumumab and combination groups. For both cell lines, panitumumab and combination groups had greater mean fluorescence of the tumor compared to control IgG. The addition of antiangiogenic therapy improves uptake of fluorescently labeled monoclonal antibodies within melanoma tumors. Clinical translation could improve detection of melanoma intraoperatively, reducing positive margins

  17. European Conference on Health Economics.

    PubMed

    Malmivaara, Antti

    2010-12-01

    The biennial European Conference on Health Economics was held in Finland this year, at the Finlandia Hall in the centre of Helsinki. The European conferences rotate among European countries and fall between the biennial world congresses organized by the International Health Economics Association (iHEA). A record attendance of approximately 800 delegates from 50 countries around the world were present at the Helsinki conference. The theme of the conference was 'Connecting Health and Economics'. All major topics of health economics were covered in the sessions. For the first time, social care economics was included in the agenda of the European Conference as a session of its own.

  18. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials).

    PubMed

    Gaudet, Daniel; Kereiakes, Dean J; McKenney, James M; Roth, Eli M; Hanotin, Corinne; Gipe, Daniel; Du, Yunling; Ferrand, Anne-Catherine; Ginsberg, Henry N; Stein, Evan A

    2014-09-01

    Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease, with limited treatment options. This analysis evaluated the effect of a monoclonal antibody to proprotein convertase subtilisin/kexin 9, alirocumab 150 mg every 2 weeks (Q2W), on Lp(a) levels in pooled data from 3 double-blind, randomized, placebo-controlled, phase 2 studies of 8 or 12 weeks' duration conducted in patients with hypercholesterolemia on background lipid-lowering therapy (NCT01266876, NCT01288469, and NCT01288443). Data were available for 102 of 108 patients who received alirocumab 150 mg Q2W and 74 of 77 patients who received placebo. Alirocumab resulted in a significant reduction in Lp(a) from baseline compared with placebo (-30.3% vs -0.3%, p <0.0001). Median percentage Lp(a) reductions in the alirocumab group were of a similar magnitude across a range of baseline Lp(a) levels, resulting in greater absolute reductions in Lp(a) in patients with higher baseline levels. Regression analysis indicated that <5% of the variance in the reduction of Lp(a) was explained by the effect of alirocumab on low-density lipoprotein cholesterol. In conclusion, pooled data from 3 phase 2 trials demonstrate substantive reduction in Lp(a) with alirocumab 150 mg Q2W, including patients with baseline Lp(a) >50 mg/dl. Reductions in Lp(a) only weakly correlated with the magnitude of low-density lipoprotein cholesterol lowering.

  19. Detecting decay fungi with antibody-based tests and immunoassays

    Treesearch

    Carol A. Clausen

    2003-01-01

    Early detection of wood decay can prolong the service life of wood. Antibodies are the ideal probe for detecting fungi that cause biodeterioration because they are highly specific and can quantitatively determine the fungal antigen concentration from highly complex structures, such as wood. Polyclonal antibodies recognize multiple chemical sites of the targeted...

  20. CD4-Induced Antibodies Promote Association of the HIV-1 Envelope Glycoprotein with CD4-Binding Site Antibodies

    PubMed Central

    Fellinger, Christoph H.; Prasad, Neha R.; Zhou, Amber S.; Kondur, Hema R.; Joshi, Vinita R.; Quinlan, Brian D.; Farzan, Michael

    2016-01-01

    ABSTRACT The HIV-1 envelope glycoprotein (Env) is a trimer of gp120/gp41 heterodimers that mediates viral entry. Env binds cellular CD4, an association which stabilizes a conformation favorable to its subsequent association with a coreceptor, typically CCR5 or CXCR4. The CD4- and coreceptor-binding sites serve as epitopes for two classes of HIV-1-neutralizing antibodies: CD4-binding site (CD4bs) and CD4-induced (CD4i) antibodies, respectively. Here we observed that, at a fixed total concentration, mixtures of the CD4i antibodies (E51 or 412d) and the CD4bs antibody VRC01 neutralized the HIV-1 isolates 89.6, ADA, SG3, and SA32 more efficiently than either antibody alone. We found that E51, and to a lesser extent 412d and 17b, promoted association of four CD4bs antibodies to the Env trimer but not to monomeric gp120. We further demonstrated that the binding of the sulfotyrosine-binding pocket by CCR5mim2-Ig was sufficient for promoting CD4bs antibody binding to Env. Interestingly, the relationship is not reciprocal: CD4bs antibodies were not as efficient as CD4-Ig at promoting E51 or 412d binding to Env trimer. Consistent with these observations, CD4-Ig, but none of the CD4bs antibodies tested, substantially increased HIV-1 infection of a CD4-negative, CCR5-positive cell line. We conclude that the ability of CD4i antibodies to promote VRC01 association with Env trimers accounts for the increase potency of VRC01 and CD4i antibody mixtures. Our data further suggest that potent CD4bs antibodies avoid inducing Env conformations that bind CD4i antibodies or CCR5. IMPORTANCE Potent HIV-1-neutralizing antibodies can prevent viral transmission and suppress an ongoing infection. Here we show that CD4-induced (CD4i) antibodies, which recognize the conserved coreceptor-binding site of the HIV-1 envelope glycoprotein (Env), can increase the association of Env with potent broadly neutralizing antibodies that recognize the CD4-binding site (CD4bs antibodies). We further show that

  1. Stereospecific antibodies to propranolol.

    PubMed

    Wang, L; Chorev, M; Feingers, J; Levitzki, A; Inbar, M

    1986-04-21

    The beta-adrenergic antagonist propranolol was activated through its side chain, coupled to bovine serum albumin, and injected into BALB/c mice. After fusion of the splenocytes from these immunized mice with the NS-1 myeloma cell line, two hybridomas, producing monoclonal anti-propranolol antibodies, were isolated. Clone P-49 was monospecific for propranolol, with a significant preference for the 1-stereoisomer, as compared to the d form. On the other hand, clone P-28 cross-reacted with alprenolol as well as some other beta-antagonists. Both classes of antibodies competed with A431 epidermoid carcinoma beta 2-adrenoceptors for the binding of [3H]propranolol. When ascites cells from clone P-28 were fixed with glutaraldehyde, the anti-propranolol monoclonal antibody became cell bound. These cell-bound P-28 antibodies bind propranolol and other beta-adrenergic ligands with a similar ranking order to the soluble monoclonal antibody. The cell-bound antibody displayed a 5-fold higher affinity towards 1-propranolol than the soluble monoclonal antibody. The practical implications of these findings are discussed.

  2. STUDIES ON ANTIBODY PRODUCTION

    PubMed Central

    White, Robert G.; Coons, Albert H.; Connolly, Jeanne M.

    1955-01-01

    After subcutaneous injection of hen's ovalbumin or diphtheria toxoid precipitated with aluminum phosphate, the production of antibody, as judged by the presence in the tissues of antibody-containing cells, proceeds partly within the regional lymphatic glands and partly in the granulation tissue surrounding the nodule which develops at the site of injection. The first production of antibody takes place in the regional lymphatic gland and antibody production in the local granuloma becomes apparent only from 14 days onwards (rabbit). Antibody-containing plasma cells were demonstrated in the local granuloma up to 7 weeks. Antibody-containing cells in the regional lymphatic glands reach maximum numbers at 2 weeks following injection and decrease thereafter to few cells at 5 weeks. The adjuvant effect of the aluminum phosphate is interpreted as due partly to the delay in absorption of antigen from the local site of its injection which results in prolongation of stimulation of cells within the regional lymphatic glands, and partly to the production of a local granuloma which contains antibody-producing plasma cells. PMID:14392242

  3. Therapeutic antibody technology 97.

    PubMed

    Larrick, J W; Gavilondo, J

    1998-01-01

    Almost 200 antibody aficionados attended the Therapeutic Antibody Technology 97 meeting, held September 21-24, 1997 at the Holiday Inn, Union Square in the heart of San Francisco, CA. The meeting was sponsored by the Palo Alto Institute of Molecular Medicine and organized by James W. Larrick (PAIMM) and Dennis R. Burton (Scripps Research Institute). The meeting featured excellent discussions on many interesting talks and a number of poster presentations. It is likely that another meeting will be organized in 2 years, however in the meantime, an effort is underway to organize a 'Virtual Antibody Society' to be set up on the web server at Scripps Research Institute in La Jolla, CA (Questions and comments on this project can be sent to: Jwlarrick@aol.com or Burton@scripps.edu). Richard Lerner (Scripps) gave the keynote address on 'Catalytic Antibodies', describing recent work with Carlos Barbas on so-called reactive immunization to generate a high activity aldolase catalytic antibody. This antibody, soon to be described in an article in Science, is the first commercially available catalytic antibody.

  4. NMDA receptor antibodies

    PubMed Central

    Ramberger, Melanie; Bsteh, Gabriel; Schanda, Kathrin; Höftberger, Romana; Rostásy, Kevin; Baumann, Matthias; Aboulenein-Djamshidian, Fahmy; Lutterotti, Andreas; Deisenhammer, Florian; Berger, Thomas

    2015-01-01

    Objectives: To analyze the frequency of NMDA receptor (NMDAR) antibodies in patients with various inflammatory demyelinating diseases of the CNS and to determine their clinical correlates. Methods: Retrospective case-control study from 2005 to 2014 with the detection of serum IgG antibodies to NMDAR, aquaporin-4, and myelin oligodendrocyte glycoprotein by recombinant live cell-based immunofluorescence assays. Fifty-one patients with acute disseminated encephalomyelitis, 41 with neuromyelitis optica spectrum disorders, 34 with clinically isolated syndrome, and 89 with multiple sclerosis (MS) were included. Due to a known association of NMDAR antibodies with seizures and behavioral symptoms, patients with those clinical manifestations were preferentially included and are therefore overrepresented in our cohort. Nine patients with NMDAR encephalitis, 94 patients with other neurologic diseases, and 48 healthy individuals were used as controls. Results: NMDAR antibodies were found in all 9 patients with NMDAR encephalitis but in only 1 of 215 (0.5%) patients with inflammatory demyelination and in none of the controls. This patient had relapsing-remitting MS with NMDAR antibodies present at disease onset, with an increase in NMDAR antibody titer with the onset of psychiatric symptoms and cognitive deficits. Conclusion: In demyelinating disorders, NMDAR antibodies are uncommon, even in those with symptoms seen in NMDAR encephalitis. PMID:26309901

  5. A Recap of the Fourth Nationwide Vocational Education Dissemination Conference. The Proceedings (Columbus, Ohio, November 17-19, 1981).

    ERIC Educational Resources Information Center

    Singer, Norman M., Comp.; Grieve, Shelley, Comp.

    These proceedings summarize the Fourth Nationwide Vocational Education Dissemination Conference that concentrated on the knowledge, tools, techniques, and topical areas needed by disseminators, linkers, and other change agents. Introductory materials are a conference overview, reflections on the conference, and the agenda. Brief summaries follow…

  6. Energy Conferences and Symposia; (USA)

    SciTech Connect

    Osborne, J.H.; Simpson, W.F. Jr.

    1991-01-01

    Energy Conferences and Symposia, a monthly publication, was instituted to keep scientists, engineers, managers, and related energy professionals abreast of meetings sponsored by the Department of Energy (DOE) and by other technical associations. Announcements cover conference, symposia, workshops, congresses, and other formal meetings pertaining to DOE programmatic interests. Complete meeting information, including title, sponsor, and contact, is presented in the main section, which is arranged alphabetically by subject area. Within a subject, citations are sorted by beginning data of the meeting. New listings are indicated by a bullet after the conference number and DOE-sponsored conferences are indicated by a star. Two indexes are provided for cross referencing conference information. The Chronological Index lists conference titles by dates and gives the subject area where complete information they may be found. The Location Index is alphabetically sorted by the city where the conference will be held.

  7. Immune deficiency enhances expression of recombinant human antibody in mice after nonviral in vivo gene transfer.

    PubMed

    Kitaguchi, Kohji; Toda, Mikako; Takekoshi, Masataka; Maeda, Fumiko; Muramatsu, Tatsuo; Murai, Atsushi

    2005-10-01

    A cDNA encoding human antibody against hepatitis B virus was expressed in normal and severe combined immune deficiency (SCID) mice to clarify whether or not host immune status affects circulating levels of the recombinant human antibody (RhAb) after nonviral in vivo gene transfer. For transferring genes, either electroporation (EP) or hydrodynamics-based transfection (HD) was employed. The former was applied to the leg muscle to express the gene, while the latter primarily targeted foreign gene expression in the liver. The expressed RhAb was secreted into the blood circulation, and its existence was assayed by ELISA. Prior to the investigation of host immune status, suitable forms of plasmid expression vectors and types of electrodes were determined in normal mice. Results showed that the vector encoding both the light and heavy chains driven by the CMV promoter had the highest plasma RhAb concentrations, and a pair of pincette-type electrodes conferred the best performance. In both EP and HD, the SCID state showed an increased and prolonged RhAb production in the blood circulation due probably to suppressed recognition of RhAb as a foreign protein to the host animal. The difference in gene transfer methods demonstrated a characteristic pattern: an early and sharp rise followed by a relatively rapid decrease in HD, in contrast to a gradual rise followed by a plateau level maintained in EP. As a result, with the same amount of gene transferred, the plasma RhAb concentrations for the first 7 or 8 weeks were higher in HD than EP, while the reverse was true for the latter period. Multiple gene transfer contributed to maintaining and prolonging high RhAb concentrations in plasma by both methods with similar characteristic patterns accompanying the respective gene transfer method. These results suggest the importance of host immunological potency for maintaining plasma RhAb concentrations if these gene transfer technologies are used for clinical and therapeutic purposes.

  8. Antibody discovery: sourcing of monoclonal antibody variable domains.

    PubMed

    Strohl, William R

    2014-03-01

    Historically, antibody variable domains for therapeutic antibodies have been sourced primarily from the mouse IgG repertoire, and typically either chimerized or humanized. More recently, human antibodies from transgenic mice producing human IgG, phage display libraries, and directly from human B lymphocytes have been used more broadly as sources of antibody variable domains for therapeutic antibodies. Of the total 36 antibodies approved by major maket regulatory agencies, the variable domain sequences of 26 originate from the mouse. Of these, four are marketed as murine antibodies (of which one is a mouse-rat hybrid IgG antibody), six are mouse-human chimeric antibodies, and 16 are humanized. Ten marketed antibodies have originated from human antibody genes, three isolated from phage libraries of human antibody genes and seven from transgenic mice producing human antibodies. Five antibodies currently in clinical trials have been sourced from camelids, as well as two from non-human primates, one from rat, and one from rabbit. Additional sources of antibody variable domains that may soon find their way into the clinic are potential antibodies from sharks and chickens. Finally, the various methods for retrieval of antibodies from humans, mouse and other sources, including various display technologies and amplification directly from B cells, are described.

  9. Monoclonal antibody "gold rush".

    PubMed

    Maggon, Krishan

    2007-01-01

    The market, sales and regulatory approval of new human medicines, during the past few years, indicates increasing number and share of new biologics and emergence of new multibillion dollar molecules. The global sale of monoclonal antibodies in 2006 were $20.6 billion. Remicade had annual sales gain of $1 billion during the past 3 years and five brands had similar increase in 2006. Rituxan with 2006 sales of $4.7 billion was the best selling monoclonal antibody and biological product and the 6th among the top selling medicinal brand. It may be the first biologic and monoclonal antibody to reach $10 billion annual sales in the near future. The strong demand from cancer and arthritis patients has surpassed almost all commercial market research reports and sales forecast. Seven monoclonal antibody brands in 2006 had sales exceeding $1 billion. Humanized or fully human monoclonal antibodies with low immunogenicity, enhanced antigen binding and reduced cellular toxicity provide better clinical efficacy. The higher technical and clinical success rate, overcoming of technical hurdles in large scale manufacturing, low cost of market entry and IND filing, use of fully human and humanized monoclonal antibodies has attracted funds and resources towards R&D. Review of industry research pipeline and sales data during the past 3 years indicate a real paradigm shift in industrial R&D from pharmaceutical to biologics and monoclonal antibodies. The antibody bandwagon has been joined by 200 companies with hundreds of new projects and targets and has attracted billions of dollars in R&D investment, acquisitions and licensing deals leading to the current Monoclonal Antibody Gold Rush.

  10. Serum thyroglobulin antibody levels within or near to the reference range may interfere with thyroglobulin measurement.

    PubMed

    Locsei, Zoltán; Szabolcs, István; Rácz, Károly; Kovács, Gábor L; Horváth, Dóra; Toldy, Erzsébet

    2012-01-01

    High concentration of thyroglobulin antibodies (TgAb) is a major limiting factor of thyroglobulin measurements in patients with differentiated thyroid cancer. We investigated whether thyroglobulin antibody added to serum samples could interfere with the thyroglobulin assay. Thyroglobulin levels in serum samples with different concentrations of thyroglobulin were measured by electrochemiluminescence immunoassay before and after the addition of increasing concentrations of thyroglobulin antibody using the secondary calibrator solution of the thyroglobulin assay kit containing sheep thyroglobulin antibody to reach thyroglobulin antibody levels within or near to the reference range. Thyroglobulin and thyroglobulin antibody concentrations were also measured in 134 serum samples from 27 patients after thyroid ablation. There was a strong negative association (slope = -1.179) between thyroglobulin antibody and thyroglobulin concentrations in samples with added thyroglobulin antibody (beta = -0.86; P <0.001). Changes in thyroglobulin concentrations were described mathematically as loss of thyroglobulin% = -0.2408 x Ln(thyroglobulin antibody IU/ml) + 0.1944. Thyroglobulin concentrations were significantly lower than those calculated from experiments with added thyroglobulin antibody in 26/134 samples from patients after thyroid ablation. We conclude that if the same TgAb interference exists in the presence of naturally occurring human TgAb, our observation may prove to be useful during follow-up of patients with differentiated thyroid cancer. However, further studies are needed to explore the clinical relevance of thyroglobulin antibody levels within or near to the reference range in monitoring these patients.

  11. PREFACE: 1982 International Conference on Plasma Physics

    NASA Astrophysics Data System (ADS)

    Wilhelmsson, Hans

    1982-01-01

    Invited Papers: The Physics of Hot Plasmas During the last decade a dramatic evolution of plasma physics has occurred. Not only have gigantic fusion plasma machines been planned, and are now being built, and elaborate spaceships and antenna systems been constructed to explore remote parts of the cosmos; new observations have revealed fascinating structures in space, ranging from pulsar plasmas under extreme conditions in very strong magnetic fields to large-scale magnetic field and electric current systems in cosmic plasmas. X-rays from very distant sources as well as radio-waves from the plasma in the magnetosphere and in the Aurora have recently been studied with new observational techniques. Ingenious laboratory experiments are continuously being carried out to exploit new fundamental processes in plasmas. These are of great interest for the basic understanding of plasmas and also have immediate consequences for applications, like plasma heating and diagnostics. The theoretical description of new plasma phenomena, and of the plasma state in general poses challenging problems, particularly in situations where high concentration of energy is located in the plasmas. Nonlinear wave analysis and turbulence theory have accordingly been extensively developed to describe in particular the collective plasma phenomena. New concepts have been envisaged like plasma solitons, which may be thought of as excitations of local concentrations of longitudinal plasma waves which turn out to be particularly stable. More and more sophisticated structures of nonlinear nature are being revealed by means of high capacity computer facilities. Simulation experiments allow for studies of chaotic behaviour of plasma particles. Related fields of activity form new trends in the development of plasma theory. The programme of the 1982 International Conference on Plasma Physics, which was held in Göteborg, Sweden, stressed the role of the Physics of Hot Plasmas. Studies of such plasmas are

  12. Antiphospholipid antibody syndrome.

    PubMed

    Kutteh, William H; Hinote, Candace D

    2014-03-01

    Antiphospholipid antibodies (aPLs) are acquired antibodies directed against negatively charged phospholipids. Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings. Obstetric APS is one of the most commonly identified causes of recurrent pregnancy loss. Thus, obstetric APS is distinguished from APS in other organ systems where the most common manifestation is thrombosis. Several pathophysiologic mechanisms of action of aPLs have been described. This article discusses the diagnostic and obstetric challenges of obstetric APS, proposed pathophysiologic mechanisms of APS during pregnancy, and the management of women during and after pregnancy.

  13. Mississippi Climate & Hydrology Conference

    SciTech Connect

    Lawford, R.; Huang, J.

    2002-05-01

    The GEWEX Continental International Project (GCIP), which started in 1995 and completed in 2001, held its grand finale conference in New Orleans, LA in May 2002. Participants at this conference along with the scientists funded through the GCIP program are invited to contribute a paper to a special issue of Journal of Geophysical Research (JGR). This special JGR issue (called GCIP3) will serve as the final report on scientific research conducted by GCIP investigators. Papers are solicited on the following topical areas, but are not limited to, (1) water energy budget studies; (2) warm season precipitation; (3) predictability and prediction system; (4) coupled land-atmosphere models; (5) climate and water resources applications. The research areas cover observations, modeling, process studies and water resources applications.

  14. Metabolic Engineering VII Conference

    SciTech Connect

    Kevin Korpics

    2012-12-04

    The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

  15. NSI conference support

    NASA Technical Reports Server (NTRS)

    Aaron, Susan

    1991-01-01

    One of the many services NSI provides as an extension of customer/user support is to attend major scientific conferences. The conference effort provides NASA/OSSA scientists with many benefits: (1) scientist get to see NSI in action; they utilize the network to read email, and have recently begun to demonstrate their scientific research to their colleagues; (2) scientist get an opportunity to meet and interact with NSI Staff, which gives scientists a chance to get status on their requirements, ask about network status, get acquainted with our procedures, and learn about services; and (3) scientists are exposed to networking in a larger sense; particularly by knowing about other NASA groups who provide valuable scientific resources over the Internet.

  16. Expedition 41 Press Conference

    NASA Image and Video Library

    2014-09-24

    Expedition 41 Soyuz Commander Alexander Samokutyaev of the Russian Federal Space Agency (Roscosmos) and Flight Engineer Elena Serova of Roscosmos hold up tiger toys that will be carried with them to the International Space Station to commemorate International Tiger Day at a press conference held at the Cosmonaut Hotel in Baikonur, Kazakhstan on Wednesday, Sept. 24, 2014. The mission is set to launch Sept. 26 from the Baikonur Cosmodrome. Photo Credit: (NASA/Aubrey Gemignani)

  17. Expedition 32 Press Conference

    NASA Image and Video Library

    2012-07-13

    Quarantined Expedition 32 JAXA (Japan Aerospace Exploration Agency) Flight Engineer Akihiko Hoshide answers reporters questions from behind glass during a prelaunch press conference held at the Cosmonaut Hotel on Friday, July 13, 2012 in Baikonur, Kazakhstan. The launch of the Soyuz spacecraft with Hoshide, Soyuz Commander Yuri Malenchenko, and NASA Flight Engineer Sunita Williams is scheduled for 8:40 a.m. local time on Sunday, July 15. Photo Credit (NASA/Carla Cioffi)

  18. Expedition 34 Press Conference

    NASA Image and Video Library

    2012-12-18

    Expedition 34/35 NASA Flight Engineer Tom Marshburn answers a reporter's question at a press conference held at the Cosmonaut Hotel, on Tuesday, Dec. 18, 2012, in Baikonur, Kazakhstan. Launch of the Soyuz rocket is scheduled for December 19 and will send Marshburn, Roman Romanenko of ROSCOSMOS and Chris Hadfield of the Canadian Space Agency on a five-month mission aboard the International Space Station. Photo Credit: (NASA/Carla Cioffi)

  19. Expedition 32 Press Conference

    NASA Image and Video Library

    2012-07-13

    Quarantined Expedition 32 JAXA (Japan Aerospace Exploration Agency) Flight Engineer Akihiko Hoshide, left, answers reporters questions from behind glass during a prelaunch press conference held at the Cosmonaut Hotel on Friday, July 13, 2012 in Baikonur, Kazakhstan. Seated next to him is Soyuz Commander Yuri Malenchenko. The launch of the Soyuz spacecraft with Hoshide, Malenchenko, and NASA Flight Engineer Sunita Williams is scheduled for 8:40 a.m. local time on Sunday, July 15. Photo Credit (NASA/Carla Cioffi)

  20. Expedition 34 Press Conference

    NASA Image and Video Library

    2012-12-18

    Expedition 34/35 Flight Engineer and Expedition 35 Commander Chris Hadfield of the Canadian Space Agency (CSA) answers a reporter's question at a press conference held at the Cosmonaut Hotel, on Tuesday, Dec. 18, 2012, in Baikonur, Kazakhstan. Launch of the Soyuz rocket is scheduled for December 19 and will send Hadfield, Tom Marshburn of NASA and Roman Romanenko of ROSCOSMOS on a five-month mission aboard the International Space Station. Photo Credit: (NASA/Carla Cioffi)

  1. Expedition 33 Press Conference

    NASA Image and Video Library

    2012-10-22

    Expedition 33 Soyuz Commander Oleg Novitskiy answers a reporters question during a press conference held at the Cosmonaut Hotel, on Monday, October 22, 2012, in Baikonur, Kazakhstan. Launch of the Soyuz rocket is scheduled for October 23 and will send Expedition 33/34 Flight Engineer Kevin Ford of NASA, Soyuz Commander Oleg Novitskiy and Flight Engineer Evgeny Tarelkin of ROSCOSMOS on a five-month mission aboard the International Space Station. Photo Credit: (NASA/Bill Ingalls)

  2. Expedition 32 Press Conference

    NASA Image and Video Library

    2012-07-13

    Quarantined Expedition 32 Soyuz Commander Yuri Malenchenko, right, answers reporters questions from behind glass during a prelaunch press conference held at the Cosmonaut Hotel on Friday, July 13, 2012 in Baikonur, Kazakhstan. Seated next to him is JAXA Flight Engineer Akihiko Hoshide. The launch of the Soyuz spacecraft with Malenchenko, NASA Flight Engineer Sunita Williams and Hoshide is scheduled for 8:40 a.m. local time on Sunday, July 15. Photo Credit (NASA/Carla Cioffi)

  3. Expedition 37 Press Conference

    NASA Image and Video Library

    2013-09-24

    Expedition 37 NASA Flight Engineer Michael Hopkins answers a reporter's question at a press conference held at the Cosmonaut Hotel, on Tuesday, Sept. 24, 2013, in Baikonur, Kazakhstan. Launch of the Soyuz rocket is scheduled for September 26 and will send Hopkins, Soyuz Commander Oleg Kotov and Russian Flight Engineer Sergei Ryazansky on a five and a half-month mission aboard the International Space Station. Photo Credit: (NASA/Carla Cioffi)

  4. Expedition 37 Press Conference

    NASA Image and Video Library

    2013-09-24

    Expedition 37 backup crewmember Alexander Skvortsov anwers a reporter’s question at a press conference held at the Cosmonaut Hotel, on Tuesday, Sept. 24, 2013, in Baikonur, Kazakhstan. Launch of the Soyuz rocket is scheduled for September 26 and will send Kotov, Hopkins and Ryazansky on a five and a half-month mission aboard the International Space Station. Photo Credit: (NASA/Carla Cioffi)

  5. Astrobiology Press Conference

    NASA Image and Video Library

    2010-12-02

    Steven Benner, a distinguished fellow at the Foundation for Applied Molecular Evolution, speaks during a press conference, Thursday, Dec. 2, 2010, at NASA Headquarters in Washington. NASA-funded astrobiology research has changed the fundamental knowledge about what comprises all known life on Earth. Researchers conducting tests in the harsh environment of Mono Lake in California have discovered the first known microorganism on Earth able to thrive and reproduce using the toxic chemical arsenic. Photo Credit: (NASA/Paul E. Alers)

  6. Astrobiology Press Conference

    NASA Image and Video Library

    2010-12-02

    Felisa Wolfe-Simon, a lead researcher and NASA astrobiology research fellow, speaks during a press conference, Thursday, Dec. 2, 2010, at NASA Headquarters in Washington. NASA-funded astrobiology research has changed the fundamental knowledge about what comprises all known life on Earth. Researchers conducting tests in the harsh environment of Mono Lake in California have discovered the first known microorganism on Earth able to thrive and reproduce using the toxic chemical arsenic. Photo Credit: (NASA/Paul E. Alers)

  7. Astrobiology Press Conference

    NASA Image and Video Library

    2010-12-02

    Felisa Wolfe-Simon, director, Astrobiology Program, NASA Headquarters, speaks during a press conference, Thursday, Dec. 2, 2010, at NASA Headquarters in Washington. NASA-funded astrobiology research has changed the fundamental knowledge about what comprises all known life on Earth. Researchers conducting tests in the harsh environment of Mono Lake in California have discovered the first known microorganism on Earth able to thrive and reproduce using the toxic chemical arsenic. Photo Credit: (NASA/Paul E. Alers)

  8. Astrobiology Press Conference

    NASA Image and Video Library

    2010-12-02

    Pamela Conrad, an astrobiologist from Goddard Space Flight Center, speaks during a press conference, Thursday, Dec. 2, 2010, at NASA Headquarters in Washington. NASA-funded astrobiology research has changed the fundamental knowledge about what comprises all known life on Earth. Researchers conducting tests in the harsh environment of Mono Lake in California have discovered the first known microorganism on Earth able to thrive and reproduce using the toxic chemical arsenic. Photo Credit: (NASA/Paul E. Alers)

  9. Military Energy Alternatives Conference

    DTIC Science & Technology

    2012-03-08

    Power Generation and Alternative Energy Branch US Army RDECOM CERDEC CP&ID Power Division Aberdeen Proving Ground, MD...RDER-CCA-PG PG A E - C R – 1 2– 0 1 M ili ta ry E ne rg y A lte rn at iv es C on fe re nc e Military Energy ...TITLE AND SUBTITLE Military Energy Alternatives Conference 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jonathan

  10. Expedition 38 Press Conference

    NASA Image and Video Library

    2013-11-06

    Expedition 38 backup crew member Reid Wiseman of NASA is seen in quarantine, behind glass, during the final press conference held a day ahead of the launch of Expedition 38 prime crew members; Flight Engineer Koichi Wakata of the Japan Aerospace Exploration Agency, Soyuz Commander Mikhail Tyurin of Roscosmos, and, Flight Engineer Rick Mastracchio of NASA, to the International Space Station, Wednesday, Nov. 6, 2013 at the Cosmonaut Hotel in Baikonur, Kazakhstan. Photo Credit: (NASA/Bill Ingalls)

  11. Expedition 41 Press Conference

    NASA Image and Video Library

    2014-09-24

    NASA Expedition 41 backup crew member Flight Engineer Scott Kelly of NASA answers a question during a press conference Wednesday, Sept. 24, 2014 at the Cosmonaut Hotel in Baikonur, Kazakhstan. Expedition 41 Flight Engineer Barry Wilmore of NASA, Soyuz Commander Alexander Samokutyaev of the Russian Federal Space Agency (Roscosmos), and Flight Engineer Elena Serova of Roscosmos are set to launch Sept. 26 from the Baikonur Cosmodrome. Photo Credit: (NASA/Aubrey Gemignani)

  12. Expedition 38 Press Conference

    NASA Image and Video Library

    2013-11-06

    Expedition 38 Soyuz Commander Mikhail Tyurin of Roscosmos, right, talks as Flight Engineer Koichi Wakata of the Japan Aerospace Exploration Agency, listens, from quarantine behind glass, during the final press conference held a day ahead of their launch with fellow crew mate, Flight Engineer Rick Mastracchio of NASA, to the International Space Station, Wednesday, Nov. 6, 2013 at the Cosmonaut Hotel in Baikonur, Kazakhstan. Photo Credit: (NASA/Bill Ingalls)

  13. Expedition 38 Press Conference

    NASA Image and Video Library

    2013-11-06

    Expedition 38 Flight Engineer Koichi Wakata of the Japan Aerospace Exploration Agency is seen in quarantine, behind glass, during the final press conference held a day ahead of his launch with fellow crew mates, Expedition 38 Soyuz Commander Mikhail Tyurin of Roscosmos, and, Flight Engineer Rick Mastracchio of NASA, to the International Space Station, Wednesday, Nov. 6, 2013 at the Cosmonaut Hotel in Baikonur, Kazakhstan. Photo Credit: (NASA/Bill Ingalls)

  14. Expedition 41 Press Conference

    NASA Image and Video Library

    2014-09-24

    Expedition 41 Flight Engineer Barry Wilmore of NASA answers a question during a press conference on Wednesday, Sept. 24, 2014, at the Cosmonaut Hotel in Baikonur, Kazakhstan. Launch of the Soyuz rocket is scheduled for Sept. 26 and will carry Wilmore, Elena Serova of the Russian Federal Space Agency (Roscosmos), and Alexander Samokutyaev of Roscosmos into orbit to begin their five and a half month mission on the International Space Station. Photo Credit: (NASA/Aubrey Gemignani)

  15. Expedition 38 Press Conference

    NASA Image and Video Library

    2013-11-06

    Expedition 38 Soyuz Commander Mikhail Tyurin of Roscosmos is seen in quarantine behind glass during the final press conference held a day ahead of his launch with fellow crew mates, Flight Engineer Koichi Wakata of the Japan Aerospace Exploration Agency, and, Flight Engineer Rick Mastracchio of NASA, to the International Space Station, Wednesday, Nov. 6, 2013 at the Cosmonaut Hotel in Baikonur, Kazakhstan. Photo Credit: (NASA/Bill Ingalls)

  16. Expedition 38 Press Conference

    NASA Image and Video Library

    2013-11-06

    Expedition 38 backup crew member Alexander Gerst of the European Space Agency is seen in quarantine, behind glass, during the final press conference held a day ahead of the launch of Expedition 38 prime crew members; Flight Engineer Koichi Wakata of the Japan Aerospace Exploration Agency, Soyuz Commander Mikhail Tyurin of Roscosmos, and, Flight Engineer Rick Mastracchio of NASA, to the International Space Station, Wednesday, Nov. 6, 2013 at the Cosmonaut Hotel in Baikonur, Kazakhstan. Photo Credit: (NASA/Bill Ingalls)

  17. Kepler Press Conference

    NASA Image and Video Library

    2009-08-05

    William Bo-Ricki, Kepler principal investigator at NASA's Ames Research Center, speaks during a press conference, Thursday, Aug. 6, 2009, at NASA Headquarters in Washington about the scientific observations coming from the Kepler spacecraft that was launched this past March. Kepler is NASA's first mission that is capable of discovering earth-sized planets in the habitable zones of stars like our Sun. Photo Credit: (NASA/Paul E. Alers)

  18. Kepler Press Conference

    NASA Image and Video Library

    2009-08-05

    Jon Morse, NASA's Astrophysics Division Director, left, speaks during a press conference, Thursday, Aug. 6, 2009, at NASA Headquarters in Washington about the scientific observations coming from the Kepler spacecraft that was launched this past March asWilliam Bo-Ricki, Kepler principal investigator at NASA's Ames Research Center, looks on. Kepler is NASA's first mission that is capable of discovering earth-sized planets in the habitable zones of stars like our Sun. Photo Credit: (NASA/Paul E. Alers)

  19. Kepler Press Conference

    NASA Image and Video Library

    2009-08-05

    Sara Seager, Professor of Planetary Science at the Massachusetts Institute of Technology, speaks during a press conference, Thursday, Aug. 6, 2009, at NASA Headquarters in Washington about the scientific observations coming from the Kepler spacecraft that was launched this past March. Kepler is NASA's first mission that is capable of discovering earth-sized planets in the habitable zones of stars like our Sun. Photo Credit: (NASA/Paul E. Alers)

  20. Constellation Program Press Conference

    NASA Image and Video Library

    2006-06-04

    NASA Administrator Michael Griffin, seated left, Scott Horowitz, NASA Associate Administrator for Exploration Systems and Jeff Hanley, Constellation Program Manager, right, are seen during a press conference outlining specific center responsibilities associated with the Constellation Program for robotic and human moon and Mars exploration, Monday, June 5, 2006, at NASA Headquarters in Washington. Dean Acosta, NASA Deputy Assistant Administrator and Press Secretary, far left, moderates the program. Photo Credit (NASA/Bill Ingalls)