Synthetic Antigen

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Conner Gorry - One of the best experts on this subject based on the ideXlab platform.

  • immunodiagnostics the convergence of biotech and public health
    MEDICC Review, 2013
    Co-Authors: Aramis Sanchez Gutierrez, Conner Gorry
    Abstract:

    Conceiving, building, maintaining and refi ning a universal health system is an inordinately complex undertaking. Its effective implementation requires everything from political will consistently and strategically applied, to accurate epidemiological data and analysis, plus quality medical education and active citizen participation. It also takes resources—fi nancial, technological, pharmaceutical and professional—a perennial challenge for a small, economically-constrained island nation like Cuba. Indeed, even some highly developed nations like the United States have yet to achieve universal health coverage. In Cuba’s case, resource scarcity itself, coupled with the need to develop a sustainable health care model suffi ciently independent of global geopolitical and economic turbulence, has, paradoxically, led to the establishment of a key health system component: a robust domestic biopharmaceutical industry.[1] A Global South leader in biotech R&D, Cuba produces innovative vaccines and therapies—many unique in the world—such as Heberprot-P, Nimotuzumab, VA-MENGOC-BC, and a Synthetic Antigen vaccine against Haemophilus infl uenzae b (Hib). [2] While these products are the headline-makers, diagnostic systems and equipment designed, built and distributed by Havana’s Immunoassay Center (CIE, the Spanish acronym) have quietly but consistently contributed to improving Cuban and global health for over two decades.

  • Dr vicente vérez bencomo, director, center for the study of Synthetic Antigens, university of havana.
    MEDICC review, 2008
    Co-Authors: Conner Gorry
    Abstract:

    Dr Vicente Verez Bencomo is a world-renowned scientist who led the team that discovered and developed the Cuban Haemophilus influenzae type b (Hib) vaccine using a Synthetic Antigen - the first of its kind in the world. Educated in Cuba, Russia, and France, Dr Verez has received numerous awards for his groundbreaking work, including the World Intellectual Property Organization's Gold Medal (2005), and the Cuban National Chemistry Award (2006). The Cuban Hib vaccine is undergoing evaluation by the World Health Organization for vaccination packages for use in the developing world. Dr Verez has published widely in international scientific journals of impact and is the Cuban representative to the International Carbohydrates Organization and Senior Member of the Cuban Academy of Sciences. He is currently Director of the Center for the Study of Synthetic Antigens, under the aegis of the University of Havana's Chemistry Department. He sat down with MEDICC Review to talk about the global burden of Haemophilus influenzae type b, what motivates him as a scientist, how Synthetic Antigens might be applied to other vaccines, and what he is currently working on.

  • Dr vicente vérez bencomo, director, center for the study of Synthetic Antigens, university of havana.
    MEDICC review, 2007
    Co-Authors: Conner Gorry
    Abstract:

    Dr Vicente Vérez Bencomo is a world-renowned scientist who led the team that discovered and developed the Cuban Haemophilus influenzae type b (Hib) vaccine using a Synthetic Antigen - the first of its kind in the world. Educated in Cuba, Russia, and France, Dr Vérez has received numerous awards for his groundbreaking work, including the World Intellectual Property Organization's Gold Medal (2005), and the Cuban National Chemistry Award (2006). The Cuban Hib vaccine is undergoing evaluation by the World Health Organization for vaccination packages for use in the developing world. Dr Vérez has published widely in international scientific journals of impact and is the Cuban representative to the International Carbohydrates Organization and Senior Member of the Cuban Academy of Sciences. He is currently Director of the Center for the Study of Synthetic Antigens, under the aegis of the University of Havana's Chemistry Department. He sat down with MEDICC Review to talk about the global burden of Haemophilus influenzae type b, what motivates him as a scientist, how Synthetic Antigens might be applied to other vaccines, and what he is currently working on.

Thomas Kodadek - One of the best experts on this subject based on the ideXlab platform.

  • targeting stereotyped b cell receptors from chronic lymphocytic leukemia patients with Synthetic Antigen surrogates
    Journal of Biological Chemistry, 2016
    Co-Authors: Mohosin Sarkar, Yun Liu, Jumpei Morimoto, Haiyong Peng, Christoph Rader, Nicholas Chiorazzi, Thomas Kodadek
    Abstract:

    Chronic lymphocytic leukemia (CLL) is a disease in which a single B-cell clone proliferates relentlessly in peripheral lymphoid organs, bone marrow, and blood. DNA sequencing experiments have shown that about 30% of CLL patients have stereotyped Antigen-specific B-cell receptors (BCRs) with a high level of sequence homology in the variable domains of the heavy and light chains. These include many of the most aggressive cases that haveIGHV-unmutated BCRs whose sequences have not diverged significantly from the germ line. This suggests a personalized therapy strategy in which a toxin or immune effector function is delivered selectively to the pathogenic B-cells but not to healthy B-cells. To execute this strategy, serum-stable, drug-like compounds able to target the Antigen-binding sites of most or all patients in a stereotyped subset are required. We demonstrate here the feasibility of this approach with the discovery of selective, high affinity ligands for CLL BCRs of the aggressive, stereotyped subset 7P that cross-react with the BCRs of several CLL patients in subset 7p, but not with BCRs from patients outside this subset.

  • Recognition of Antigen-Specific B-Cell Receptors from Chronic Lymphocytic Leukemia Patients by Synthetic Antigen Surrogates
    Chemistry & Biology, 2014
    Co-Authors: Mohosin Sarkar, Yun Liu, Jumpei Morimoto, Haiyong Peng, Claudio Aquino, Christoph Rader, Nicholas Chiorazzi, Thomas Kodadek
    Abstract:

    Summary In patients with chronic lymphocytic leukemia (CLL), a single neoplastic Antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop Synthetic surrogates of the CLL Antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe nonpeptidic molecules capable of targeting Antigen-specific B cell receptors with good affinity and selectivity using a combinatorial library screen. We demonstrate that our hit compounds act as Synthetic Antigen surrogates and recognize CLL cells and not healthy B cells. Additionally, we argue that the technology we developed can be used to identify other classes of Antigen surrogates.

Bruno Gander - One of the best experts on this subject based on the ideXlab platform.

  • tetanus toxoid and Synthetic malaria Antigen containing poly lactide poly lactide co glycolide microspheres importance of polymer degradation and Antigen release for immune response
    Journal of Controlled Release, 1996
    Co-Authors: Claudio Thomasin, Giampietro Corradin, Hans P Merkle, Bruno Gander
    Abstract:

    Abstract The importance of in vitro degradation of poly(lactide)/poly(lactide-co-glycolide) (PLA/PLGA) microspheres and of the concomitant in vitro release of a natural and a Synthetic Antigen for eliciting immune response was studied in mice. A variety of PLAs and PLGAs differing in molecular weight ( M w of 14–130 kDa) and in polymer composition (lactic/glycolic acid ratio of 100:00, 75:25, and 50:50) were examined for their in vitro degradation, which ranged from approximately 4 to 20 weeks. Three specific polymers were then selected for microencapsulation of the two Antigens tetanus toxoid (TT) and a weakly immunogenic Synthetic branched malaria peptide (P30B2). The in vitro release data showed that Antigen delivery correlates fairly well with polymer degradation giving rise to a distinct burst release during the first 24 h and an additional release pulse towards the end of polymer degradation. After single subcutaneous administration in mice, long lasting high antibody titers were obtained with the Antigen containing microspheres, as compared to TT adsorbed on alum or to P30B2 in Incomplete Freund's Adjuvant. Moreover, the immune responses induced by microspheres were clearly influenced by the Antigen release kinetics, the polymer type and the size of the microspheres. The results demonstrate the immunopotentiating properties of the biodegradable microspheres and their potential to elicit long-lasting immune responses after single administration when tailoring in vitro release characteristics and particle size.

Mohosin Sarkar - One of the best experts on this subject based on the ideXlab platform.

  • targeting stereotyped b cell receptors from chronic lymphocytic leukemia patients with Synthetic Antigen surrogates
    Journal of Biological Chemistry, 2016
    Co-Authors: Mohosin Sarkar, Yun Liu, Jumpei Morimoto, Haiyong Peng, Christoph Rader, Nicholas Chiorazzi, Thomas Kodadek
    Abstract:

    Chronic lymphocytic leukemia (CLL) is a disease in which a single B-cell clone proliferates relentlessly in peripheral lymphoid organs, bone marrow, and blood. DNA sequencing experiments have shown that about 30% of CLL patients have stereotyped Antigen-specific B-cell receptors (BCRs) with a high level of sequence homology in the variable domains of the heavy and light chains. These include many of the most aggressive cases that haveIGHV-unmutated BCRs whose sequences have not diverged significantly from the germ line. This suggests a personalized therapy strategy in which a toxin or immune effector function is delivered selectively to the pathogenic B-cells but not to healthy B-cells. To execute this strategy, serum-stable, drug-like compounds able to target the Antigen-binding sites of most or all patients in a stereotyped subset are required. We demonstrate here the feasibility of this approach with the discovery of selective, high affinity ligands for CLL BCRs of the aggressive, stereotyped subset 7P that cross-react with the BCRs of several CLL patients in subset 7p, but not with BCRs from patients outside this subset.

  • Recognition of Antigen-Specific B-Cell Receptors from Chronic Lymphocytic Leukemia Patients by Synthetic Antigen Surrogates
    Chemistry & Biology, 2014
    Co-Authors: Mohosin Sarkar, Yun Liu, Jumpei Morimoto, Haiyong Peng, Claudio Aquino, Christoph Rader, Nicholas Chiorazzi, Thomas Kodadek
    Abstract:

    Summary In patients with chronic lymphocytic leukemia (CLL), a single neoplastic Antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop Synthetic surrogates of the CLL Antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe nonpeptidic molecules capable of targeting Antigen-specific B cell receptors with good affinity and selectivity using a combinatorial library screen. We demonstrate that our hit compounds act as Synthetic Antigen surrogates and recognize CLL cells and not healthy B cells. Additionally, we argue that the technology we developed can be used to identify other classes of Antigen surrogates.

Claudio Thomasin - One of the best experts on this subject based on the ideXlab platform.

  • tetanus toxoid and Synthetic malaria Antigen containing poly lactide poly lactide co glycolide microspheres importance of polymer degradation and Antigen release for immune response
    Journal of Controlled Release, 1996
    Co-Authors: Claudio Thomasin, Giampietro Corradin, Hans P Merkle, Bruno Gander
    Abstract:

    Abstract The importance of in vitro degradation of poly(lactide)/poly(lactide-co-glycolide) (PLA/PLGA) microspheres and of the concomitant in vitro release of a natural and a Synthetic Antigen for eliciting immune response was studied in mice. A variety of PLAs and PLGAs differing in molecular weight ( M w of 14–130 kDa) and in polymer composition (lactic/glycolic acid ratio of 100:00, 75:25, and 50:50) were examined for their in vitro degradation, which ranged from approximately 4 to 20 weeks. Three specific polymers were then selected for microencapsulation of the two Antigens tetanus toxoid (TT) and a weakly immunogenic Synthetic branched malaria peptide (P30B2). The in vitro release data showed that Antigen delivery correlates fairly well with polymer degradation giving rise to a distinct burst release during the first 24 h and an additional release pulse towards the end of polymer degradation. After single subcutaneous administration in mice, long lasting high antibody titers were obtained with the Antigen containing microspheres, as compared to TT adsorbed on alum or to P30B2 in Incomplete Freund's Adjuvant. Moreover, the immune responses induced by microspheres were clearly influenced by the Antigen release kinetics, the polymer type and the size of the microspheres. The results demonstrate the immunopotentiating properties of the biodegradable microspheres and their potential to elicit long-lasting immune responses after single administration when tailoring in vitro release characteristics and particle size.