2024-03-28T18:13:25+04:30 http://vacres.pasteur.ac.ir/browse.php?mag_id=3&slc_lang=en&sid=1
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Vaccine Research vacres 2383-2819 2423-4923 10.52547/vacres 2015 2 1 Highlights of the final draft of the national policy document for science, technology and innovation in vaccine production in Iran P Owlia owlia@yahoo.com M Ghanei mghanei@hbi.ir SM Mirafzali SD Siadat S Malekifar H Esmailzadeh H Saderi Introduction: Vaccination has been the most effective human intervention in alleviating human sufferings and death. Vaccine production in Iran has a long history however, in the face of a changing global landscape, it requires a new roadmap for research, development and production in the coming decades. Methods: This document was drafted based on Article A of the “Comprehensive National Scientific Roadmap”, in compliance with priorities laid out in the primary directives as well as the key concerns of the stakeholders outlined in the 20-year vision for the country, the fifth development plan, the Comprehensive National Scientific Roadmap and the Scientific map of Health System. In addition, policies of various developed and developing countries, related WHO publications and published literature on policymaking were reviewed to obtain data pertaining to topics such as the current vaccine landscape, historical and current trends, the challenges and obstacles in vaccine research, development and production as aids to decision making. Results: In the course of several sessions, the selected panel outlined the vision, mission, expected outcome, main objectives and the founding principles of the national policy document for science, technology and innovation in vaccine production in Iran. In addition, guidelines in areas of policymaking, management and laws, financial resource allocation, knowledge production, publication and knowledge sharing, human resources, expansion in product manufacturing and services, entrepreneurship and communication were outlined. Conclusion: Vaccine production in Iran is facing many challenges and to become a successful player in the global vaccine market, it requires implementation of the guidelines that have been outlined in this draft. Remaining a supplier of traditional vaccine to the domestic market, in the face of increasing competition from the emerging manufacturers, is not a viable option for this industry. Vaccine production policymaking Iran 2015 5 01 1 5 http://vacres.pasteur.ac.ir/article-1-47-en.pdf 10.18869/acadpub.vacres.2.3.1
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Vaccine Research vacres 2383-2819 2423-4923 10.52547/vacres 2015 2 1 Impact of vaccination on epidemiology of diphtheria and pertussis N Guiso nicole.guiso@pasteur.fr Whooping cough and diphtheria are vaccine preventable diseases. Diphtheria, due to Corynebacterium diphtheriae or Corynebactium ulcerans, two Gram positive bacteria, is a serious upper respiratory tract disease with high morbidity and mortality rates. Vaccination, via an acellular vaccine composed only of purified, detoxified diphtheria toxin, has significantly reduced the incidence of the disease in most of the developed world. However, the lower vaccine coverage of diphtheria vaccination in adults is now a cause for concern. Furthermore, the disease remains endemic in many developing countries where the vaccine coverage is low. Whooping cough, due to Bordetella pertussis or Bordetella parapertussis, two Gram negative bacteria, is a severe and highly contagious respiratory disease. The use of pertussis whole cell vaccines, containing inactivated bacteria, or later on pertussis acellular vaccines, only containing one to five purified, detoxified bacterial proteins, reduced dramatically the incidence of the morbidity and mortality. However, despite a high coverage the disease is still endemic in many regions of the world. Explaining this epidemiologic situation is, however, difficult since pertussis, vaccines, strategies, coverage, awareness of the disease and surveillance systems differ around the world. It is thus urgent to establish reference laboratories around the world using standardized clinical diagnosis and specific and sensitive diagnostic methods. vaccination epidemiology diphtheria pertussis 2015 5 01 6 8 http://vacres.pasteur.ac.ir/article-1-48-en.pdf 10.18869/acadpub.vacres.2.3.6
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Vaccine Research vacres 2383-2819 2423-4923 10.52547/vacres 2015 2 1 Molecular analysis of AbOmpA type-1 as immunogenic target for therapeutic interventions against MDR Acinetobacter baumannii infection F Badmasti fbadmasti2008@gmail.com SD Siadat d.siadat@gmail.com S Bouzari bouzari@pasteur.ac.ir O Nasiri H Nemati F Shahcheraghi shahcheraghifereshteh@yahoo.com Introduction: Acinetobacter baumannii is associated with hospital-acquired infections. Outer membrane protein A of A.baumannii (AbOmpA) is a well-characterized virulence factor which has important roles in pathogenesis of this bacterium. Methods: Based on our PCR-sequencing of ompA gene in the clinical isolates, AbOmpA protein can be categorized into two types, named here type-1 and type-2. We preformed in silico analyses on beta-barrel domain of AbOmpA such as sequence alignments, prediction of 3D modeling and immunoinformatics. Results: High prevalence of AbOmpA type-1 were detected both in 21 multidrug-resistant (MDR) A. baumannii isolates collected from clinical settings (64% of total sequences) and in silico sequences extracted from Uniprot database (49.7% of total sequences). Multiple sequence alignments and phylogenic tree revealed AbOmpA sequences in comparison with OmpA of Enterobacteriaceae family were more heterogenic, especially at extracellular loops amino acid positions and were evolutionary far from this family. Characterization of in silico 3D molecular model of beta-barrel domain of AbOmpA type-1 showed this domain had four large extracellular loops which resemble to beta-barrel domain of Klebsiella pneumonia OmpA (KpOmpA). Immunoinformatics analyses showed the four extracellular loops had high scores as B and T cell antigenic epitopes especially in loop-1 and 3. Geometry analysis revealed extracellular loops effectively protrude to outer space of the cell. Conclusion: Beta-barrel domain of AbOmpA type-1 has all the characteristics of a promising vaccine and could be considered as an excellent target for a vaccine against MDR A. baumannii infection. beta-barrel domain of AbOmpA Alignment phylogenic tree in silico 3D molecular model epitope prediction 2015 5 01 9 18 http://vacres.pasteur.ac.ir/article-1-49-en.pdf 10.18869/acadpub.vacres.2.3.9
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Vaccine Research vacres 2383-2819 2423-4923 10.52547/vacres 2015 2 1 Allelic variations between vaccine strains and circulating strains in pxtP of Bordetella pertussis in Iran F Sadeghpour Heravi f.sadeghpour1989@gmail.com VS Nikbin F Shahcheraghi shahcheraghifereshteh@yahoo.com Introduction: Despite high level of vaccination against pertussis‚ whooping cough has re-emerged as a health threat, especially in infants. This could be related to expansion of Bordetella pertussis with novel alleles for virulence factors including the pertussis toxin promoter, ptxP3. Compared to ptxp1 strains‚ ptxp3 strains produce more pertussis toxin which results in immune suppression and virulence. The main aim of this study was the determination of dominant alleles of the promoter region of the gene coding for pertussis toxin in B. pertussis isolates in Iran. Methods: In this project, we studied the allelic variations in ptxP3 .This factor was sequenced and analyzed in 35 B. pertussis isolates from Iranian patients in 2011. Biochemical tests were performed to confirm the B. pertussis isolates. Ultimately, polymerase chain reactions and sequencing were done. Results: Our results showed that the predominant allele among the strains was ptxP3. One isolated strain (i.e. ptxP1) showed different results from the other strains. Also, B. pertussis 134 and 509 as common vaccine strains used in Iran were analyzed and they were identified to be ptxP1. Conclusion: Based on our results in recent years‚ the vaccine strains and the circulating strains do not share the same alleles which could be one of the causes of pertussis resurgence in the world. ptxP is a well-known toxin of B. pertussis which is responsible for binding to the host cell and the disruption of the cellular function. In particular‚ allelic variation in ptxP may play a role in adaption of B. pertussis. Bordetella pertussis virulence factors polymorphism vaccine. 2015 5 01 19 23 http://vacres.pasteur.ac.ir/article-1-51-en.pdf 10.18869/acadpub.vacres.2.3.19
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Vaccine Research vacres 2383-2819 2423-4923 10.52547/vacres 2015 2 1 Construction of pIRES2 vector encoding truncated NS3 of HCV and IL-18 for DNA vaccine studies M Zavvar mahdi.zavvar@gmail.com A Moshiri F Motevali fatememotevalli@gmail.com MH Pouriayevali mhpouriayevali@yahoo.com G Bahramali gbahramali@gmail.com Introduction: Long term complications of hepatitis C virus (HCV) infection include fibrosis, cirrhosis, and hepatocellular carcinoma and although the disease is treatable with the newly introduced direct acting antivirals, but factors such as drug resistance, viral genotype and adverse effects can limit the effectiveness of therapy. Therefore, development of effective, safe and affordable prophylactic and therapeutic vaccines is a global goal. This study was undertaken for construction of a vector containing the coding region for  a truncated form of nonstructural protein 3 (NS3) of HCV and IL-18 cytokine gene fused to murine Fcy2a as molecular adjuvantfor assessmentas a DNA vaccine candidate.  Methods: A truncated form of NS 3 was amplified and cloned in pIRES2 containing IL-18 hybrid gene. Expression of the truncated NS3 and bioactivity of IL-18 fusion protein were assessed in transfected HEK293 T cells. Physicochemical properties determination, secondary structure, 3D modelingand T-cell epitope predictionswere made using various online tools. Results: In silico analysis of truncated NS3 predicted a molecular weight of 32.35 kDa containing epitopic regions with the highest scores for binding to MHC complex. 3D model of IL-18showed that fusion with murine Fc had not impaired the structure. HEK293 T cells were successfully transfected with pIRES-IL18-NS3construct and expression of truncated NS3 with an apparent molecular weight of approximately 32 kDa was confirmed by Western blotting.  Conclusion: Despite the advantages, widespread use of DNA vaccination has been hampered by low immunogenicity. Truncated NS3 was expressed albeit in low amount with bioactive IL-18 fusion proteinas a molecular adjuvant Immunogenicity assessment of this novel combination as a DNA vaccine candidate is underway. HCV NS3 IL18 DNA vaccine Adjuvant 2015 5 01 24 28 http://vacres.pasteur.ac.ir/article-1-55-en.pdf 10.18869/acadpub.vacres.2.3.24
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Vaccine Research vacres 2383-2819 2423-4923 10.52547/vacres 2015 2 1 Shelf-life estimation of recombinant hepatitis B vaccine using R software in comparison with WHO manual protocol SM Hosseini SB Momen d Doroud d_doroud@yahoo.com SN Hoseini K Maboudi Sh Hadadian hadadian@ yahoo.com Introduction: Pharmaceutical companies as well as food and cosmetics manufacturers are legally required to provide a shelf-life label on their products packaging as part of their stability study report. There are different recommended software like R software package and SAS which can perform as shelf-life estimating tools for analyzing the data achieved by the stability testing of drugs and vaccines. Methods: Recombinant hepatitis B surface antigen vaccine (Pasteur Institute of Iran) was used as a sample for the entire quality control assays according to Pharmacopeia and NIH (National Institute of Health) procedures. For the stability study, full test examinations were done and R software package was applied to estimate the shelf-life. Results: The results of R software indicated a variety of statistical information which makes the data interpretation more intelligible and apprehensible. Conclusion: Based on our results and experience, the best way to obtain a shelf-life or the expiration date is to calculate it manually however, using software such as R can increase the accuracy of the results. ICH FDA Hepatitis B vaccine shelf-life expiration date. 2015 5 01 29 32 http://vacres.pasteur.ac.ir/article-1-60-en.pdf 10.18869/acadpub.vacres.2.3.29
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Vaccine Research vacres 2383-2819 2423-4923 10.52547/vacres 2015 2 1 Assessment of humoral immune response of a Cytomegalovirus DNA-vaccine candidate in BALB/c mice R Vahabpour farhang_v_r@yahoo.com MR Aghasadeghi mr_sadeqi@yahoo.com F Goudarzifar H Keyvani A Ataei- Pirkooh SH Monavari hrmonavari@yahoo.com M Eslami Introduction: Glycoprotein B (gB) is the major antigen for induction of humoral responses against human cytomegalovirus (HCMV) making it an attractive candidate for immune prophylaxis. In the present study, the humoral immune response of BALB/c mice to a truncated HCMV gB protein fused with GFP was evaluated. Methods: The truncated gB coding sequence was synthesized and cloned in pEGFPN1 eukaryotic expression vector and expressed in HEK 293T cell line. After optimization, expression of the recombinant truncated HCMV gB was verified using HRP-conjugated polyclonal antibody specific for HCMV gB.The level of humoral immune responses was assessed in mice using DNA/DNA,  peptide/peptide, and DNA/ peptide (prime-boost) immunization strategies. Results: Cloning of the truncated gB coding sequence in the pEGFPN1 was verified by restriction enzyme analysis and sequencing. After optimizing the transfection procedure the number of the GFP positive cells reached 32%. Western blot analysis confirmed the in vitro expression of the truncated HCMV gB protein with an apparent molecular weight of approximately 70 kDa. In vivo prime-boost immunization using HCMV gB DNA/peptide regimen showed significantly higher humoral immune responses compared to the control groups. Conclusion: This study demonstrated that the pEGFPN1 eukaryotic expression vector could be used to optimize and evaluate the expression of this truncated protein.The results also showed that the DNA/peptide vaccination could induce a significant antibody response in animal model. human cytomegalovirus Glycoprotein B DNA-based vaccine. 2015 5 01 33 37 http://vacres.pasteur.ac.ir/article-1-61-en.pdf 10.18869/acadpub.vacres.2.3.33
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Vaccine Research vacres 2383-2819 2423-4923 10.52547/vacres 2015 2 1 Overview of the validation procedures for a vaccine production: from R;D level to the pre-qualification stage H Kaghazian kaghazianh@gmail.com D Doroud d_doroud@yahoo.com Just like any other process, vaccine manufacturing procedures are defined as a series of interrelated functions and activities using a variety of specified actions and equipment designed to produce a defined product. To assure the reproducibility and consistency of such processes, they must be carried out using validated equipment and under the established procedures that meet all the acceptance criteria, at least 3 times. In many cases, “worst case” conditions are used for the validation purposes to ensure that the process would be acceptable in extreme cases. Therefore, the validation concept in vaccine production facilities is a key element of the quality assurance goals which may reduce the dependence upon intensive in-process and finished products testing. Nevertheless, the concept of validation has expanded through the years to embrace a wide range of activities such as analytical methods used for quality control of drugs, the computerized systems for the clinical trials, the labeling and the process control. To perform such validation activities properly, the updated knowledge of the current regulations are needed. Therefore, the present article focuses on the recommendations in the related guidelines addressing different aspects of validation procedures related to the vaccine production facilities as a part of the product’s life-cycle. Validation GMP Process Analytical Method Regulation. 2015 5 01 38 44 http://vacres.pasteur.ac.ir/article-1-62-en.pdf 10.18869/acadpub.vacres.2.3.38