biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Products10.30895/2221-996X-2023-23-1-26-41biopreparat-447Research ArticleСтатьиБезопасность и иммуногенность вакцины третьего поколения IMVAMUNE® на основе вируса вакцины, штамм MVASafety and immunogenicity of IMVAMUNE®, a third-generation vaccine based on the modified vaccinia Ankara (MVA) strainhttps://orcid.org/0000-0002-7985-5516СтовбаЛ. Ф.StovbaL. F.

Стовба Людмила Федоровна, канд. биол. наук

ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306

Lyudmila F. Stovba, Cand. Sci. (Biol.)

11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306

48cnii@mil.ruhttps://orcid.org/0000-0002-2603-0860ЧухраляО. В.ChukhralyaO. V.

Чухраля Олег Васильевич

ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306

Oleg V. Chukhralya

11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306

48cnii@mil.ruhttps://orcid.org/0000-0002-1491-6293ЧерниковаН. К.ChernikovaN. K.

Черникова Наталья Константиновна, канд. биол. наук

ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306

Natalya K. Chernikova, Cand. Sci. (Biol.)

11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306

48cnii@mil.ruhttps://orcid.org/0000-0002-6686-320XХмелевА. Л.KhmelevA. L.

Хмелев Алексей Леонидович, канд. мед. наук

ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306

Aleksey L. Khmelev, Cand. Sci. (Med.)

11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306

hmeleval@mail.ruhttps://orcid.org/0000-0002-6742-3919БорисевичС. В.BorisevichS. V.

Борисевич Сергей Владимирович, д-р биол. наук, проф., акад. РАН

ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306

Sergey V. Borisevich, Dr. Sci. (Biol.), Professor, Academician of RAS

11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306

48cnii@mil.ruФедеральное государственное бюджетное учреждение «48 Центральный научно-исследовательский институт» Министерства обороны Российской ФедерацииРоссия48 Central Scientific Research InstituteRussian Federation202321022023231Вопросы разработки новых противовирусных вакцин2641Copyright © Стовба Л.Ф., Чухраля О.В., Черникова Н.К., Хмелев А.Л., Борисевич С.В., 20232023Стовба Л.Ф., Чухраля О.В., Черникова Н.К., Хмелев А.Л., Борисевич С.В.Stovba L.F., Chukhralya O.V., Chernikova N.K., Khmelev A.L., Borisevich S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.biopreparations.ru/jour/article/view/447

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.

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).

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The authors declare that there are no conflicts of interest present.