Safety and immunogenicity of IMVAMUNE®, a third-generation vaccine based on the modified vaccinia Ankara (MVA) strain

In 1980, the World Health Assembly officially declared smallpox eradicated in the world, which allowed developed countries to stop preventive vaccination against this disease. However, circulating and emerging orthopoxviruses along with the lack of herd immunity prompt the need for emergency smallpox vaccines meeting the current requirements for biologicals.The aim of the study was to analyse the safety and efficacy of third-generation smallpox vaccines based on the MVA strain of vaccinia virus compliant with the current (stricter) immunogenicity and safety requirements in healthy subjects and especially in patients with underlying health conditions, considering the lack of herd immunity to orthopoxviruses.The authors analysed the existing experience with smallpox vaccines. The vaccines based on the modified vaccinia Ankara (MVA) strain hold a special place amongst other third-generation vaccines, as this strain is safe and can be used for creating vector vaccines. Bavarian Nordic produces the MVA-based vaccine under three brand names (Imvanex in the EU, Jynneos™ in the USA, and IMVAMUNE® in Canada). According to the results of MVA-based vaccine clinical trials in healthy volunteers and patients with various underlying conditions, the main mild adverse drug reactions (erythema, pain, pruritus, and swelling) were mostly registered at the injection site. The systemic adverse drug reactions included fatigue, headache, myalgia, and chills; several subjects developed upper respiratory tract infections, nausea, and gastroenteritis, which resolved spontaneously within a day. MVA-based vaccines did not cause any cardiac abnormalities, including myo- or pericarditis. Thus, the vaccines may be used in patients with eczema, atopic dermatitis, inflammatory skin conditions, HIV, tuberculosis, cardiac abnormalities, as well as in children, adolescents, and pregnant women. The optimal intradermal immunisation dose was 1×108 TCID50. Two injections at this dose induced a pronounced humoral and cell-mediated immune response comparable to that induced by one administration of a first-generation smallpox vaccine. At this dose, the study vaccine also boosted pre-existing immunity conferred by a first-generation vaccine. The US Centers for Disease Control and Prevention recommend Jynneos™ for preventing monkeypox in adults (18 years of age and older)

Безопасность и иммуногенность вакцины третьего поколения IMVAMUNE® на основе вируса вакцины, штамм MVA

In 1980, the World Health Assembly officially declared smallpox eradicated in the world, which allowed developed countries to stop preventive vaccination against this disease. However, circulating and emerging orthopoxviruses along with the lack of herd immunity prompt the need for emergency smallpox vaccines meeting the current requirements for biologicals.The aim of the study was to analyse the safety and efficacy of third-generation smallpox vaccines based on the MVA strain of vaccinia virus compliant with the current (stricter) immunogenicity and safety requirements in healthy subjects and especially in patients with underlying health conditions, considering the lack of herd immunity to orthopoxviruses.The authors analysed the existing experience with smallpox vaccines. The vaccines based on the modified vaccinia Ankara (MVA) strain hold a special place amongst other third-generation vaccines, as this strain is safe and can be used for creating vector vaccines. Bavarian Nordic produces the MVA-based vaccine under three brand names (Imvanex in the EU, Jynneos™ in the USA, and IMVAMUNE® in Canada). According to the results of MVA-based vaccine clinical trials in healthy volunteers and patients with various underlying conditions, the main mild adverse drug reactions (erythema, pain, pruritus, and swelling) were mostly registered at the injection site. The systemic adverse drug reactions included fatigue, headache, myalgia, and chills; several subjects developed upper respiratory tract infections, nausea, and gastroenteritis, which resolved spontaneously within a day. MVA-based vaccines did not cause any cardiac abnormalities, including myo- or pericarditis. Thus, the vaccines may be used in patients with eczema, atopic dermatitis, inflammatory skin conditions, HIV, tuberculosis, cardiac abnormalities, as well as in children, adolescents, and pregnant women. The optimal intradermal immunisation dose was 1×108 TCID50. Two injections at this dose induced a pronounced humoral and cell-mediated immune response comparable to that induced by one administration of a first-generation smallpox vaccine. At this dose, the study vaccine also boosted pre-existing immunity conferred by a first-generation vaccine. The US Centers for Disease Control and Prevention recommend Jynneos™ for preventing monkeypox in adults (18 years of age and older).В 1980 г. Всемирная ассамблея здравоохранения официально провозгласила искоренение натуральной оспы в мире, что позволило в развитых странах отменить профилактическую вакцинацию против этого заболевания. Однако из-за постоянно циркулирующих и вновь возникающих ортопоксвирусов, а также отсутствия популяционного иммунитета необходимо наличие в чрезвычайных ситуациях противооспенных вакцин, отвечающих современным требованиям к иммунобиологическим препаратам.Цель работы — анализ безопасности и эффективности в условиях отсутствия популяционного иммунитета к ортопоксвирусам оспенной вакцины третьего поколения на основе штамма MVA вируса вакцины, отвечающей повышенным требованиям иммуногенности и безопасности, особенно с учетом применения ее для лиц с отклонениями в состоянии здоровья. Проанализирован опыт применения противооспенных вакцин. Среди противооспенных вакцин третьего поколения особое место занимает вакцина на основе вируса вакцины, штамм MVA (modified vaccinia virus Ankara), выпускаемая компанией Bavarian Nordic под тремя названиями (в Европе — Imvanex, в США — Jynneos™, в Канаде — IMVAMUNE®), поскольку он безопасен и может использоваться для конструирования векторных вакцин. Результаты клинических исследований вакцины на основе штамма MVA на здоровых добровольцах и лицах с различными отклонениями в здоровье показали, что основные побочные реакции легкой степени тяжести (эритема, болезненность, зуд, припухлость) в основном регистрировали в месте введения вакцины. Из системных побочных реакций отмечены утомление, головная боль, миалгия, озноб; у незначительной части — инфекция верхних дыхательных путей, тошнота, гастроэнтерит, которые самопроизвольно проходили в течение первых суток. Вакцина не вызывает нарушений сердечной деятельности, включая миоперикардит, может быть применена для лиц с экземой, атопическим дерматитом и воспалительными кожными заболеваниями, ею можно вакцинировать ВИЧ-инфицированных, больных туберкулезом, лиц с нарушениями сердечной деятельности, а также детей младшего возраста, подростков и беременных женщин. Определена оптимальная иммунизирующая доза вакцины при внутрикожном введении, равная 1×108 ЦПД50. Выявлено, что при двукратном введении в данной дозе вакцина индуцирует выраженный гуморальный и клеточный иммунный ответ, сопоставимый по уровню с иммунитетом после однократного введения вакцины первого поколения, а также бустирует иммунитет, ранее сформировавшийся при иммунизации противооспенной вакциной первого поколения. Вакцина Jynneos™ в настоящее время одобрена CDC (США) для профилактики оспы обезьян у взрослых в возрасте 18 лет и старше

ВЛИЯНИЕ МНОГОСТЕННЫХ НАНОТРУБОК НА ПРИВИВКУ ТРАНС-ЭТИЛЕН-1,2-ДИКАРБОНОВОЙ КИСЛОТЫ К МАКРОМОЛЕКУЛАМ ПОЛИОЛЕФИНОВ

A study was conducted on the effect of multiwalled carbon nanotubes (MWNT) on the course of free-radical grafting of trans-ethylene-1,2-dicarboxylic acid (TEDA) onto linear low-density polyethylene (LLDPE) and ethylene-propylene copolymer (cPP), containing ethylene units ≈ 7 wt%, using the reactive extrusion process. The extrusion reactor was the material cylinder of the twin-screw extruder TSSK-35/40 (screw diameter = 35 mm; L/D = 40; 10 independent heating zones).It was found that small amounts of MWNT (0.01–0.3 wt%) influence noticeably the monomer grafting onto macromolecules of LLDPE and cPP, as well as the structure, functionalized products’ mechanical properties, strength and high elasticity properties of their melts. The extent of MWNT influence depends on their concentration and PO-structure. It is shown that the monomer’s grafting efficiency can be raised with MWNT ≥ 0.1 wt% inhibit the secondary process of macromolecular cross-linking; in the case of cPP which mostly undergoes degradation during functionalization, the secondary reactions accelerate catalytically.Исследовано влияние многостенных нанотрубок (МУНТ) на протекание свободнорадикальной прививки транс-этилен-1,2-дикарбоновой кислоты к линейному полиэтилену низкой плотности (ЛПЭНП) и сополимеру этилена с пропиленом (сПП) с содержанием звеньев этилена ≈7 масс. %, осуществляемой методом реакционной экструзии. В качестве экструзионного реактора использовали материальный цилиндр двухшнекового экструдера TSSK-35/40 (диаметр шнеков 35 мм, L/D = 40, число независимых зон обогрева 10).Установлено, что малые добавки МУНТ (0,01–0,3 масс. %) оказывают заметное влияние на ход прививки мономера к макромолекулам ЛПЭНП и сПП, а также структуру, механические свойства функционализированных продуктов, прочность и высокоэластичность их расплавов. Степень влияния добавок МУНТ определяется их концентрацией и природой ПО. Показана возможность повышения эффективности прививки мономера при концентрации МУНТ в реакционной системе ≈0,05 масс. %.Для сшивающегося при свободнорадикальной прививке ЛПЭНП добавки МУНТ, вводимые в количестве ≥0,1 масс. %, ингибируют побочный процесс сшивания макромолекул, а для сПП, преимущественно деструктирующего при функционализации, наблюдается каталитическое ускорение побочных реакций

Experience in the Design and Production of Recombinant Oral Vaccine «Revax VZT»

Objective of the work was the production of recombinant vaccine «RevaxVZT» in tablet dosage form against hepatitis B and pathogenic for humans orthopoxviruses for further clinical trials. Materials and methods. Recombinant strain b7.5S2-S of vaccinia virus carrying a DNA fragment of hepatitis B virus inserted into thymidinekinase gene was used as an active component of the vaccine. Microbiological, virological, physical, physical and chemical, and biotechnological methods were used for studying the quality of the drug and technological processes. Results and discussion. Results of technological control for semi-finished products and final products of the vaccine “Revax VZT” showed the possibility of using certified hardware-processing line of “TEOVac” for its manufacturing. Same technology can be potentially used with other live tableted embryo smallpox vaccines too. For the development of the vaccine “Revax VZT” with the specific activity of not less than 1.0·107 PFu/tablet, it is necessary to use a dry virus-containing material with activity not less than 2.0·108 PFU/g which is produced by freeze-drying of liquid virus-containing preparation with the activity of not less than 1.0·108 PFU/g, preferentially propagated from chorionic allantoic membranes of chicken embryos as a substrate for viral biomass accumulation

Approaches to Reduce Adverse Effect of Vaccinia Virus in Orally Immunized Mice

Objective of the investigation was to model the adverse action of vaccinia virus (VV), caused by oral immunization of mice and to evaluate efficacy of its reduction, using therapeutic and prophylactic drugs. Materials and methods. Virological and immunological research methods were used. Results and conclusions. Reproduced was pathological action of VV in the orally infected mice. The ability to reduce the side effect and protect mice from lethal infection was demonstrated by such preparations as Metisazon, Likopid, and NIOCH-14 orally administered in the investigated schemes. Moreover preliminary single oral immunization with TEOVak smallpox vaccine before oral infection with Neurovaccine-92 strain of VV also lowered pathogenic effect and protected mice against death. All the investigated schemes of drug administration did not affect the immune response if used alongside with TEOVak smallpox vaccine and can be deployed to develop safe schemes of primary oral vaccination against smallpox. In addition, such drugs as Ribomunil, Immudon, Ingavirin can be used as means to enhance the immune response to smallpox vaccines