公开(公告)号：US20120129199A1

公开(公告)日：2012-05-24

申请号：US13321521

申请日：2010-05-19

申请人： Pirouz M. Daftarian ,  Paolo Serafini ,  Vance Paul Lemmon ,  Angel Kaifer ,  Bonnie Beth Blomberg ,  Raquibul Chowdhury ,  Norma Kenyon

发明人： Pirouz M. Daftarian ,  Paolo Serafini ,  Vance Paul Lemmon ,  Angel Kaifer ,  Bonnie Beth Blomberg ,  Raquibul Chowdhury ,  Norma Kenyon

IPC分类号： G01N33/566 ,  C12N5/078

CPC分类号： G01N33/54346 ,  C12N15/87 ,  C12N2810/85 ,  G01N33/505 ,  G01N33/56977 ,  G01N33/6866 ,  G01N2333/57 ,  G01N2333/70539 ,  G01N2500/04

摘要： Nanoparticle-based compositions, assays, kits, methods and platforms for delivering an antigen (peptides, proteins) or a nucleic acid encoding an antigen to professional APCs (PAPCs) result in the generation of autologous APCs that present a natural peptide repertoire of the antigen for use in assessing the efficacy of a vaccine (e.g., a cytotoxic T lymphocyte (CTL) response to a particular antigen) or other therapy or intervention (cell-based therapy, adjuvant therapy, etc.). The compositions, kits, assays and methods also can be used for delivering a drug or biologic or portion thereof to APCs for assessing the immunogenicity of drugs and biologics. The composition, kits, assays and methods involve the combined use of MHC targeting, universal DR binding peptides (e.g., PADRE, HA) with charged (e.g., positively-charged) highly branched polymeric dendrimers (e.g., PAMAM and other dendrimers) as vehicles for the targeted delivery of nucleic acids, peptides, biologics, drugs, or polypeptides to APCs, giving rise to a new nanoparticle-based method for assessing the immune response (CTL response) to a vaccination or other therapy or intervention, or for assessing the immunogenicity of a biologic or drug. Targeted delivery of nucleic acids, peptides, biologics, drugs, or polypeptides to APCs for effective expression and processing generates more physiologically relevant target antigens for evaluation of cell-mediated immune responses to vaccination, for example, and provides a low-cost approach for rapid generation of reagents and development of assay systems for more accurate profiling of immunological responses to infection, immunization, and other therapies or interventions. Immunoevaluation kits using targeted nanoparticle-based antigen delivery are described herein.

公开(公告)号：US09764012B2

公开(公告)日：2017-09-19

申请号：US13262285

申请日：2010-04-01

申请人： Pirouz M. Daftarian ,  Paolo Serafini ,  Vance Paul Lemmon ,  Angel Kaifer ,  Victor Perez ,  Wei Li ,  Bonnie Beth Blomberg

发明人： Pirouz M. Daftarian ,  Paolo Serafini ,  Vance Paul Lemmon ,  Angel Kaifer ,  Victor Perez ,  Wei Li ,  Bonnie Beth Blomberg

IPC分类号： A61K39/395 ,  A61K39/00 ,  A61K39/145 ,  C08G83/00 ,  A61K39/12

CPC分类号： A61K39/0011 ,  A61K39/12 ,  A61K39/145 ,  A61K2039/53 ,  A61K2039/55516 ,  A61K2039/55555 ,  A61K2039/645 ,  C08G83/006 ,  C12N2760/16022 ,  C12N2760/16034 ,  G01N2333/70539

摘要： Nanoparticle-based vaccines, compositions, kits and methods are used for the effective delivery of one or more antigens in vivo for vaccination and antibody (e.g., monoclonal antibody) production, and for the effective delivery of peptides, proteins, siRNA, RNA or DNA to PAPCs or MHC class II positive cells (e.g. tumor cells). Antigens may be, for example, DNA that results in expression of the gene of interest and induction of a robust and specific immune response to the expressed protein in a subject (e.g., mammal). Antigens may also be immunogenic peptides or polypeptides that are processed and presented. In one embodiment, a nanoparticle-based method to deliver antigens in vivo as described herein includes injection of a vaccine composed of a DNA encoding at least one antigen, or at least one antigenic peptide or polypeptide conjugated to a charged dendrimer (e.g., PADRE-derivatized dendrimer) that is also conjugated to a T helper epitope (e.g., PADRE). Negatively-charged plasmids bind naturally to a positively-charged PADRE-dendrimer, while peptide or polypeptide antigens can be chemically linked to the PADRE-dendrimer if they are not negatively-charged. Alternatively, negatively-charged dendrimers may be used. The compositions, kits, vaccines and methods described herein have both prophylactic and treatment applications, i.e., can be used as a prophylactic to prevent onset of a disease or condition in a subject, as well as to treat a subject having a disease or condition. A vaccine as described herein can be used to mount an immune response against any infectious pathogen or cancer.

公开(公告)号：US20120093761A1

公开(公告)日：2012-04-19

申请号：US13262285

申请日：2010-04-01

申请人： Pirouz M. Daftarian ,  Paolo Serafini ,  Vance Paul Lemmon ,  Angel Kaifer ,  Victor L. Perez ,  Wei Li ,  Bonnie Beth Blomberg

发明人： Pirouz M. Daftarian ,  Paolo Serafini ,  Vance Paul Lemmon ,  Angel Kaifer ,  Victor L. Perez ,  Wei Li ,  Bonnie Beth Blomberg

IPC分类号： A61K31/785 ,  A61P35/00 ,  C12N15/09 ,  A61P37/04 ,  C08G69/48 ,  C12N5/07

CPC分类号： A61K39/0011 ,  A61K39/12 ,  A61K39/145 ,  A61K2039/53 ,  A61K2039/55516 ,  A61K2039/55555 ,  A61K2039/645 ,  C08G83/006 ,  C12N2760/16022 ,  C12N2760/16034 ,  G01N2333/70539

摘要： Nanoparticle-based vaccines, compositions, kits and methods are used for the effective delivery of one or more antigens in vivo for vaccination and antibody (e.g., monoclonal antibody) production, and for the effective delivery of peptides, proteins, siRNA, RNA or DNA to PAPCs or MHC class II positive cells (e.g. tumor cells). Antigens may be, for example, DNA that results in expression of the gene of interest and induction of a robust and specific immune response to the expressed protein in a subject (e.g., mammal). Antigens may also be immunogenic peptides or polypeptides that are processed and presented. In one embodiment, a nanoparticle -based method to deliver antigens in vivo as described herein includes injection of a vaccine composed of a DNA encoding at least one antigen, or at least one antigenic peptide or polypeptide conjugated to a charged dendrimer (e.g., PADRE-derivatized dendrimer) that is also conjugated to a T helper epitope (e.g., PADRE). Negatively-charged plasmids bind naturally to a positively-charged PADRE-dendrimer, while peptide or polypeptide antigens can be chemically linked to the PADRE-dendrimer if they are not negatively-charged. Alternatively, negatively-charged dendrimers may be used. The compositions, kits, vaccines and methods described herein have both prophylactic and treatment applications, i.e., can be used as a prophylactic to prevent onset of a disease or condition in a subject, as well as to treat a subject having a disease or condition. A vaccine as described herein can be used to mount an immune response against any infectious pathogen or cancer.

摘要翻译： 使用基于纳米粒子的疫苗，组合物，试剂盒和方法在体内有效递送一种或多种抗原用于疫苗接种和抗体（例如，单克隆抗体）生产，以及有效递送肽，蛋白质，siRNA，RNA或DNA 到PAPC或MHC II类阳性细胞（例如肿瘤细胞）。 抗原可以是例如导致感兴趣的基因的表达的DNA，并且在受试者（例如哺乳动物）中诱导对所表达的蛋白质的鲁棒和特异性免疫应答。 抗原也可以是被处理和呈递的免疫原性肽或多肽。 在一个实施方案中，如本文所述的在体内递送抗原的基于纳米颗粒的方法包括注射由编码至少一种抗原的DNA组成的疫苗，或至少一种与带电树枝状大分子缀合的抗原肽或多肽（例如PADRE- 衍生的树枝状大分子），其也缀合到T辅助表位（例如，PADRE）。 带负电荷的质粒天然地与带正电荷的PADRE-树枝状大分子结合，而肽或多肽抗原如果不带负电荷则可与PADRE-树枝状大分子化学连接。 或者，可以使用带负电的树枝状聚合物。 本文描述的组合物，试剂盒，疫苗和方法具有预防和治疗应用，即可用作预防剂以预防受试者中疾病或病症的发作，以及治疗患有疾病或病症的受试者。 本文所述的疫苗可以用于抵抗任何感染性病原体或癌症的免疫应答。