RESUMO
In February this year, about 100 delegates gathered for three days in Vienna (Austria) for the Next Generation Vaccines conference. The meeting held in the Vienna Hilton Hotel from 23rd-25th February 2011 had a strong focus on biotech and industry. The conference organizer Jacob Fleming managed to put together a versatile program ranging from the future generation of vaccines to manufacturing, vaccine distribution and delivery, to regulatory and public health issues. Carefully selected top industry experts presented first-hand experience and shared solutions for overcoming the latest challenges in the field of vaccinology. The program also included several case study presentations on novel vaccine candidates in different stages of development. An interactive pre-conference workshop as well as interactive panel discussions during the meeting allowed all delegates to gain new knowledge and become involved in lively discussions on timely, interesting and sometimes controversial topics related to vaccines.
Assuntos
Vacinação/tendências , Vacinas , Humanos , Saúde Pública , Vacinas contra a Tuberculose , Vacinação/métodos , Vacinas/administração & dosagem , Vacinas/imunologiaRESUMO
The potential of empty bacterial cell envelopes (ghosts) as a delivery system for mucosal immunization was assessed in a rat model and different routes of immunization were evaluated. Animals were mucosally immunized targeting either gut only or gut and lung mucosal sites with Escherichia coli ghosts harbouring the nontypeable Haemophilus influenzae (NTHi) antigen Omp26. Omp26 was expressed as either a part of an S-layer fusion or as a soluble protein in the periplasm. In the gut/lung regime two initial gut targeted inoculations with the ghosts were followed by an intratracheal (IT) boost with purified Omp26. The gut only immunization regime showed a moderate enhancement of bacterial clearance following pulmonary challenge whereas the gut/lung immunization regime resulted in significantly enhanced pulmonary clearance of NTHi. Both immunization regimes induced high levels of Omp26 specific antibodies in the serum of immunized rats, with higher levels in the groups that received the IT boost with purified Omp26. Analysis of IgG isotypes present in serum suggest that the immune response was predominantly of a T-helper1 type. Additionally, immunization induced a significant cellular immune response with lymphocytes from animals vaccinated using the gut/lung regime responding significantly to Omp26 when compared to control groups. The results of this study show that mucosal immunization with recombinant Omp26 in E. coli ghosts followed by a boost with purified Omp26 can induce a specific and protective immune response in a rodent model of acute lung infection.
Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Anti-Haemophilus/imunologia , Glicoproteínas de Membrana/imunologia , Administração por Inalação , Administração Oral , Animais , Anticorpos Antibacterianos/sangue , Proteínas da Membrana Bacteriana Externa/genética , Portadores de Fármacos/administração & dosagem , Escherichia coli/genética , Escherichia coli/imunologia , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/genética , Imunização Secundária/métodos , Imunoglobulina G/sangue , Linfócitos/imunologia , Masculino , Glicoproteínas de Membrana/genética , Ratos , Células Th1/imunologia , Vacinação/métodos , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologiaRESUMO
Adenosine deaminases that act on RNA (ADARs) convert adenosines to inosine in both coding and noncoding double-stranded RNA. Deficiency in either ADAR1 or ADAR2 in mice is incompatible with normal life and development. While the ADAR2 knockout phenotype can be attributed to the lack of editing of the GluR-B receptor, the embryonic lethal phenotype caused by ADAR1 deficiency still awaits clarification. Recently, massive editing was observed in noncoding regions of mRNAs in mice and humans. Moreover, editing was observed in protein-coding regions of four mRNAs encoding FlnA, CyFip2, Blcap, and IGFBP7. Here, we investigate which of the two active mammalian ADAR enzymes is responsible for editing of these RNAs and whether any of them could possibly contribute to the phenotype observed in ADAR knockout mice. Editing of Blcap, FlnA, and some sites within B1 and B2 SINEs clearly depends on ADAR1, while other sites depend on ADAR2. Based on our data, substrate specificities can be further defined for ADAR1 and ADAR2. Future studies on the biological implications associated with a changed editing status of the studied ADAR targets will tell whether one of them turns out to be directly or indirectly responsible for the severe phenotype caused by ADAR1 deficiency.
Assuntos
Adenosina Desaminase/metabolismo , Edição de RNA , RNA Mensageiro/metabolismo , Transcrição Gênica , Proteínas Adaptadoras de Transdução de Sinal , Adenosina Desaminase/genética , Animais , Sequência de Bases , Filaminas , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Proteínas de Neoplasias/genética , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA , Elementos Nucleotídeos Curtos e Dispersos/genética , Especificidade por SubstratoRESUMO
This study has investigated the feasibility of a combination of recombinant surface layer (S-layer) proteins and empty bacterial cell envelopes (ghosts) to deliver candidate antigens for a vaccine against nontypeable Haemophilus influenzae (NTHi) infections. The S-layer gene sbsA from Bacillus stearothermophilus PV72 was used for the construction of fusion proteins. Fusion of maltose binding protein (MBP) to the N-terminus of SbsA allowed expression of the S-layer in the periplasm of Escherichia coli. The outer membrane protein (Omp) 26 of NTHi was inserted into the N-terminal and C-terminal regions of SbsA. The presence of the fused antigen Omp26 was demonstrated by Western blot experiments using anti-Omp26 antisera. Electron microscopy showed that the recombinant SbsA maintained the ability to self-assemble into sheet-like and cylindrical structures. Recombinant E. coli cell envelopes (ghosts) were produced by the expression of SbsA/Omp26 fusion proteins prior to gene E-mediated lysis. Intraperitoneal immunization with these recombinant bacterial ghosts induced an Omp26-specific antibody response in BALB/c mice. These results demonstrate that the NTHi antigen, Omp26, was expressed in the S-layer self-assembly product and this construct was immunogenic for Omp26 when administered to mice in bacterial cell envelopes.
Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas de Bactérias/imunologia , Membrana Celular/imunologia , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae/imunologia , Proteínas de Membrana/imunologia , Proteínas Recombinantes de Fusão/imunologia , Animais , Anticorpos Antibacterianos/sangue , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bacteriólise , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/fisiologia , Vetores Genéticos , Infecções por Haemophilus/imunologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/imunologia , Haemophilus influenzae/classificação , Haemophilus influenzae/genética , Imunização , Masculino , Proteínas Ligantes de Maltose , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismoRESUMO
Recent advances in the development of immunotherapeutic mAbs for cancer New vaccine reduces malaria infection by 72% Bavarian Nordic's cancer immunotherapy shows promise in colorectal cancer Chinese HFMD vaccine shows high efficacy in Phase 3 Two-dose regimen of Merck's Gardasil looks effective Accelerating influenza vaccine development using synthetic biology A key role for gut microbes in vaccination Understanding of and attitudes towards vaccines: a study in teenagers.
Assuntos
Vacinas Anticâncer/uso terapêutico , Neoplasias Colorretais/terapia , Vacinas contra Influenza/uso terapêutico , Malária/terapia , Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/imunologia , Antígeno CTLA-4/imunologia , Humanos , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/imunologiaRESUMO
Vaccinating boys against HPV to reduce cancer rates across the sexes: New melanoma vaccine contains natural product from marine sponges: Impact of Hib conjugate vaccines in developing countries: Electronic Health Records to keep track of immunization status: Pregnant women urged to get whooping cough vaccination: New nano-coating developed to preserve vaccines: Alternative approach to creating a universal flu vaccine: New modular vaccine design: MAPS technology.
Assuntos
Infecções Bacterianas/prevenção & controle , Armazenamento de Medicamentos/métodos , Sistemas Computadorizados de Registros Médicos/estatística & dados numéricos , Melanoma/terapia , Tecnologia Farmacêutica/métodos , Vacinas/imunologia , Viroses/prevenção & controle , Animais , Portadores de Fármacos/administração & dosagem , Feminino , Humanos , Masculino , Gravidez , Vacinas/administração & dosagemRESUMO
Infant rotavirus vaccination provides for herd immunity Nonreplicating sporozoite vaccine protects humans against malaria Personalized brain cancer vaccine enters phase 2 trial Novel implantable therapeutic cancer vaccine to be tested in humans Clostridium difficile vaccine candidate successful in phase 1 CDC reports strong uptake of HPV vaccine in boys Whooping cough outbreak in Texas.