Chikungunya vaccines: advances in the development and prospects for marketing approval

Chikungunya fever is an acute infectious disease caused by the mosquito-borne Chikungunya virus (CHIKV). In the last decades, cases of the disease have been reported in more than 100 countries; therefore, CHIKV presents a global public health problem. CHIKV genotypes have limited antigenic diversity, and documented reinfection is very rare. Hence, a vaccine could prevent infection and potential disability, as well as reduce the epidemic spread of CHIKV in the population.The aim of the study was to review approaches to the development of preventive vaccines against CHIKV, evaluate promising vaccine candidates in preclinical or clinical development stages, and analyse perspectives and challenges of bringing these vaccines to the pharmaceutical market.According to the literature reviewed, both traditional and modern platforms are used in the development of CHIKV vaccines, which has been ongoing for several decades. Each platform has its advantages and limitations. The most popular platforms are live attenuated vaccines and vaccines with viral vector constructs. To date, about 25 vaccine candidates have successfully passed through preclinical studies, and more than 7 vaccine candidates have progressed to various phases of clinical studies. The preventive medicinal products that have reached the clinical development stage include 4 live attenuated vaccines, 1 inactivated vaccine, 1 vaccine containing virus-like particles, and 1 mRNA vaccine. All 7 candidates have demonstrated cross-protection against multiple genotypes of CHIKV at the level of either preclinical in vivo studies and/or clinical in vitro studies. The research continues, and this shows that not only the scientific community but also health systems are interested in bringing effective CHIKV vaccines to the pharmaceutical market

The effect of irradiation on the magnetic properties of rock and synthetic samples: Implications to irradiation of extraterrestrial materials in space

© 2015, Pleiades Publishing, Ltd. We report here the results of laboratory analog experiments to consider the potential effects of solar energetic particles (SEP or solar-flare-associated particles) and galactic cosmic rays (GCR) on the magnetic properties of extraterrestrial materials. We carried out proton bombardment experiments (with irradiation energies E1=400, E2 =850 keV and three irradiation fluences in 1014–1016p/cm2 range) and lead-ion bombardment experiments (E =1 GeV) on (previously demagnetized by 120 mT alternating magnetic field) rock and synthetic samples with the following magnetic carriers: metallic iron and nickel iron, Ti-rich and Ti-free magnetite, pyrrhotite. Irradiation experiments resulted in either further demagnetization or magnetization of irradiated samples depending on the type of magnetic mineralogy and type of ionizing radiation involved. Apart for the formation of radiation-induced remanent magnetization (RIRM), we observed major changes in bulk magnetic properties, i.e., a moderate to dramatic decrease (up to 93%) in the coercivity of remanence Bcr for all iron-bearing phases (iron-in-epoxy and Bensour meteorite samples). Contrary to iron-bearing samples, several magnetite-bearing samples experienced a radiation-induced magnetic hardening (increase in Bcr). Magnetic hardening was also observed for Ar2+ ion-irradiated nickel iron-bearing HED meteorites, measured for comparison with the previously stated results. Therefore, the combined effect of SEP with GCR may magnetically soften iron-bearing materials and harden magnetite-bearing materials. In order to answer the question wether RIRM may account for natural remanent magnetization of meteorites and lunar samples, physical mechanism of RIRM formation and potential dependence of RIRM intensity on the background magnetic field present during irradiation event should be investigated

Estimated Inpatient Hospital Stay in Individual Wards: Guidelines on Radiation Safety after Radioiodine Therapy

Radionuclide therapy safety requirements are regulated by the Russian Radiation Safety Standards (RRSS), which state the maximum allowed radionuclide activity in the body and the equivalent dose rate (EDR) of gamma radiation. Therefore, it is necessary to estimate the time of an inpatient hospital stay in specially designed radionuclide therapy wards. The article presents the findings of individual 131I biokinetics studies in 64 patients admitted to radioiodine therapy of thyrotoxicosis and differentiated thyroid cancer. We developed a method to calculate the time interval to reach the EDR of 20μSv/h and the recommended EDR of 3 and 0.3μSv/h for adults and children, respectively. It is based on the measurement of the 131I excretion constant. Keywords: Radioiodine therapy, Radiation safety, Guidelin

Analysis of pneumococcal serotypes distribution to determine a model composition for a Russian pneumococcal conjugate vaccine

Diseases caused by Streptococcus pneumoniae, as well as antibiotic resistance of its serotypes, are the leading cause of death amongst children worldwide. To prevent pneumococcal infection, the population is immunised with conjugate vaccines containing different amounts of polysaccharides of certain serotypes. Development of a full-cycle Russian vaccine is vital because the active pharmaceutical ingredients for the vaccines registered in the Russian Federation are produced abroad, and only the final stages of production of vaccines of this group are performed in the territory of the Russian Federation. Considering the phenomenon of serotype replacement associated with the long-term widespread use of pneumococcal conjugate vaccines, it is necessary to carefully select the serotype composition for the new vaccine. The aim of this work was to analyse the serotype distribution of pneumococci in the Russian Federation and other countries in order to select optimal serotypes for the Russian vaccine for human use, taking into account vaccination schedules for each age group. This review presents an analysis of the pneumococcal serotype distribution in the Russian Federation in the pre-vaccination era, as well as after the introduction of routine vaccination. In addition, the review includes data on the serotype distribution in the Eurasian Economic Union countries. The authors described a model composition containing at least sixteen serotypes. It will increase effectiveness of immune protection of the population, providing a more complete coverage of serotypes, considering their prevalence in the Russian Federation. Based on the analysis, the serotype composition for the sixteen-valent pneumococcal conjugate vaccine is proposed for further production and preclinical and clinical trials. A new Russian pneumococcal conjugate vaccine will ensure vaccination of all population groups within the National Immunisation Schedule of the Russian Federation

Isolation and genetic analysis of the chikungunya virus from Aedes aegypti and Aedes albopictus mosquitoes captured in Central America

Introduction. The habitat of mosquitoes belonging to the genera Aedes spp., Culex spp., Culiseta spp. is in South and Central America, including Nicaragua. Monitoring of the spread of mosquito vectors and assessment of the infection with arboviruses can provide information on possible occurrence of new diseases or an increase in the reported cases, changes in the infectivity of viruses for humans due to changes in pathogen transmitters. The purpose of this study was isolation and identification of arboviruses belonging to the Flavivirus and Alphavirus genera from A. albopictus, A. aegypti, Culiseta spp., Culex spp. mosquitoes captured in forests of Nicaragua. Materials and methods. A. albopictus, A. aegypti, Culiseta spp., Culex spp. mosquitoes were captured during the dry season in 2021 in forested areas of Nicaragua in four different locations. Mosquitoes were sorted into pools, each containing 5-8 mosquitoes (236 pools in total). Using the reverse transcription polymerase chain reaction, the pools were tested for the presence of chikungunya (CHIKV), dengue, Zika, and yellow fever viruses. Positive pools were inoculated into the C6/36 cell culture to obtain isolates and for their further sequencing. Results. The dengue virus was detected only in Aedes spp. mosquitoes: in 7 pools — A. aegypti, in 1 — A. albopictus. CHIKV was also detected only in Aedes spp. mosquitoes: in 3 pools — A. aegypti, in 1 — A. albopictus. The sequencing of nucleotide sequences of 6К, Е1, Е2, and NS1 genes of CHIKV isolated from A. albopictus mosquitoes showed that compared to the similar gene sequences from CHIKV isolates recovered from A. aegypti mosquitoes, the 6K gene region contained 4 nucleotide and 4 amino acid substitutions, while the E1 region contained 16 nucleotide substitutions, 10 of them led to amino acid substitutions; the E2 region contained 14 nucleotide and 11 amino acid substitutions; the NS1 region contained 33 nucleotide and 19 amino acid substitutions

Прогресс в разработке вакцин для профилактики лихорадки Чикунгунья и перспективы появления на рынке

Chikungunya fever is an acute infectious disease caused by the mosquito-borne Chikungunya virus (CHIKV). In the last decades, cases of the disease have been reported in more than 100 countries; therefore, CHIKV presents a global public health problem. CHIKV genotypes have limited antigenic diversity, and documented reinfection is very rare. Hence, a vaccine could prevent infection and potential disability, as well as reduce the epidemic spread of CHIKV in the population.The aim of the study was to review approaches to the development of preventive vaccines against CHIKV, evaluate promising vaccine candidates in preclinical or clinical development stages, and analyse perspectives and challenges of bringing these vaccines to the pharmaceutical market.According to the literature reviewed, both traditional and modern platforms are used in the development of CHIKV vaccines, which has been ongoing for several decades. Each platform has its advantages and limitations. The most popular platforms are live attenuated vaccines and vaccines with viral vector constructs. To date, about 25 vaccine candidates have successfully passed through preclinical studies, and more than 7 vaccine candidates have progressed to various phases of clinical studies. The preventive medicinal products that have reached the clinical development stage include 4 live attenuated vaccines, 1 inactivated vaccine, 1 vaccine containing virus-like particles, and 1 mRNA vaccine. All 7 candidates have demonstrated cross-protection against multiple genotypes of CHIKV at the level of either preclinical in vivo studies and/or clinical in vitro studies. The research continues, and this shows that not only the scientific community but also health systems are interested in bringing effective CHIKV vaccines to the pharmaceutical market.Лихорадка Чикунгунья представляет собой острое инфекционное заболевание, которое вызывается вирусом Чикунгунья (ЧИКВ) и распространяется комарами. В последние десятилетия эта инфекция зарегистрирована в более чем 100 странах и превратилась в глобальную проблему для здравоохранения. В связи с тем что антигенные различия между генотипами ЧИКВ незначительны и повторные случаи инфицирования практически не регистрируют, вакцина могла бы не только предотвратить заболевание и возможную потерю трудоспособности, но и уменьшить эпидемическое распространение ЧИКВ среди населения.Цель работы — анализ направлений разработки вакцинных препаратов для профилактики лихорадки Чикунгунья, оценка перспективных препаратов, вышедших на этапы доклинических (ДКИ) и клинических исследований (КИ), а также анализ перспектив и проблем вывода препаратов на фармацевтический рынок.Анализ научной литературы показал, что при разработке вакцин, продолжающейся уже несколько десятилетий, используются как традиционные, так и новейшие технологические платформы. Каждая технологическая платформа имеет свои недостатки и преимущества. На данном этапе около 25 разработок достаточно успешно прошли этап ДКИ и более 7 находятся на разных стадиях КИ. Самыми популярными являются платформа живых аттенуированных вакцин, а также платформа вакцин с использованием векторных конструкций. Препараты, находящиеся в разных фазах КИ, представлены живыми аттенуированными вакцинами (четыре препарата), инактивированным (один препарат), содержащим вирусоподобные частицы (один препарат) и созданным на основе мРНК (один препарат). Для всех семи вакцин была продемонстрирована перекрестная защита от штаммов ЧИКВ разных генотипов или на стадии ДКИ in vivo и/или на стадии КИ in vitro. Исследования продолжаются, что подтверждает наличие не только научного интереса, но также ожиданий системы здравоохранения к выводу на фармацевтический рынок эффективных вакцин против лихорадки Чикунгунья

Особенности механизмов защиты прав на интеллектуальную собственность на примере лекарственных средств, применяемых для лечения редких (орфанных) заболеваний

Objective: to study features of intellectual property protection mechanisms on the example of drugs for the treatment of rare (orphan) diseases.Material and methods. Analysis of pharmaceutical market data was performed with the DSM Group analytical database. The approach proposed by the Russian Federal Industrial Property Service was used for creating patent landscape. The method supposes conducting a patent search and analysis of the documents found for date of filing, office (country) of filing, applicant, as well as analysis of the patent activity (dynamics) for the subject, in this case, for orphan drugs having a defined structure.Results. We proposed the complex conclusions to increase national drug safety. Intellectual property limitations for importing countries such as data exclusivity, do not allow to reproduce clinical trials, which leads to non-disclosure of medical data to all parties – medical society and patients, all other market participants, including local pharmaceutical producers. Current intellectual property restrictions conceal crucial data from medical and patient society and other market players and affect accuracy of diagnosis and treatment. Along with outstanding cost of new therapies it causes enormous budget burden for the healthcare system and prevents the introduction of objective criteria in the appointment and use of medicines. Prior to the approval and submission of the registration certificate by the regulatory authority, it is necessary to establish reasonable marginal prices, to form a sufficient set and volume of clinical guidelines and to determine in advance the sources of financing and mechanisms of integration into the national system of drug provision.Conclusion. The introduction of drugs for the treatment of rare diseases into circulation leads to a sharp increase in the burden on the budgets of the healthcare system at all levels. Current restrictions and obligations in the field of intellectual property rights protection, the degree of disclosure of medical data in the process of registration and admission to the market require significant changes to the traditional system of drug provision and the system of placing state orders, as well as the introduction of new regulatory mechanisms (for example, compulsory licensing or producing individual dosage forms in pharmacy organizations), contributing to the development of the local pharmaceutical industry and providing the national health system with the necessary volume of drugs with a sufficient level of quality and safety.Цель: изучение особенностей обеспечения защиты прав на интеллектуальную собственность на примере лекарственных средств, применяемых для лечения редких (орфанных) заболеваний.Материал и методы. Анализ данных фармацевтического рынка выполнен с использованием аналитических баз данных DSM Group. Для построения патентного ландшафта применена методика, предложенная Федеральной службой по интеллектуальной собственности. Методика предполагает проведение патентного поиска и анализ найденных документов по датам подачи, ведомству (стране) подачи и заявителю, а также анализ патентной активности (динамики) в отношении объекта, в данном случае препаратов определенной структуры для лечения орфанного заболевания.Результаты. Сформулированы выводы комплексного характера, которые направлены на повышение национальной лекарственной безопасности. Ограничения, связанные с защитой прав на интеллектуальную собственность для стран-импортеров, в частности режим эксклюзивности данных, не позволяют странам-импортерам воспроизводить клинические исследования и приводят к сокрытию таких данных от медицинских, пациентских сообществ и других участников рынка. Существующие ограничения затрудняют научный обмен между медицинскими организациями и регуляторами, влияют на точность диагностики и лечения, что в случае высокой стоимости новых методов терапии создает огромную бюджетную нагрузку на систему здравоохранения и препятствует внедрению объективных критериев при назначении и применении лекарственных средств. До момента утверждения и предоставления регистрационного удостоверения регулирующим органом необходимо устанавливать обоснованные предельные цены, формировать достаточный комплект и объем клинических рекомендаций, а также заранее определять источники финансирования и механизмы интеграции в национальную систему лекарственного обеспечения.Заключение. Введение в оборот препаратов для терапии редких заболеваний приводит к резкому увеличению нагрузки на бюджеты системы здравоохранения всех уровней. Существующие ограничения и обязательства в области защиты прав на интеллектуальную собственность, степень раскрытия медицинских данных в процессе регистрации и допуска на рынок требуют существенных изменений традиционной системы лекарственного обеспечения и системы размещения государственного заказа, а также внедрения новых регуляторных механизмов (например, принудительного лицензирования или изготовления отдельных лекарственных форм в условиях аптечных организаций), способствующих развитию локальной фармацевтической отрасли и обеспечивающих национальную систему здравоохранения необходимым объемом лекарственных средств с достаточным уровнем качества и безопасности