microbeПроблемы особо опасных инфекцийProblems of Particularly Dangerous Infections0370-10692658-719XRussian Research Anti-Plague Institute “Microbe”10.21055/0370-1069-2024-3-42-50microbe-2040Research ArticleОБЗОРЫREVIEWSПротивооспенная вакцина LC16m8: получение, свойства, перспективыSmallpox Vaccine LC16m8: Production, Properties, and Prospectshttps://orcid.org/0000-0002-7985-5516СтовбаЛ. Ф.StovbaL. F.

Российская Федерация, 141306, Московская обл., Сергиев Посад-6, ул. Октябрьская, 11

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306, Russian Federation

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

Российская Федерация, 141306, Московская обл., Сергиев Посад-6, ул. Октябрьская, 11

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306, Russian Federation

48cnii@mil.ruhttps://orcid.org/0000-0002-9714-2085ПетровА. А.PetrovA. A.

Российская Федерация, 141306, Московская обл., Сергиев Посад-6, ул. Октябрьская, 11

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306, Russian Federation

48cnii@mil.ruМельниковС. А.Mel’nikovS. A.

ORCID: https://orcid.org/0000-0003-3487-5829

Российская Федерация, 141306, Московская обл., Сергиев Посад-6, ул. Октябрьская, 11

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306, Russian Federation

48cnii@mil.ruhttps://orcid.org/0000-0003-3204-1897ПавельевД. И.Pavel’evD. I.

Российская Федерация, 141306, Московская обл., Сергиев Посад-6, ул. Октябрьская, 11

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306, Russian Federation

48cnii@mil.ruhttps://orcid.org/0000-0002-6742-3919БорисевичС. В.BorisevichS. V.

Борисевич Сергей Владимирович

Российская Федерация, 141306, Московская обл., Сергиев Посад-6, ул. Октябрьская, 11

11, Oktyabrskaya St., Sergiev Possad-6, Moscow Region, 141306, Russian Federation

48cnii@mil.ruФГБУ «48 Центральный научно-исследовательский институт» Министерства обороны Российской ФедерацииРоссия48th Central Research Institute of the Ministry of Defense of the Russian FederationRussian Federation202428092024034250Copyright © Стовба Л.Ф., Чухраля О.В., Петров А.А., Мельников С.А., Павельев Д.И., Борисевич С.В., 20242024Стовба Л.Ф., Чухраля О.В., Петров А.А., Мельников С.А., Павельев Д.И., Борисевич С.В.Stovba L.F., Chukhralya O.V., Petrov A.A., Mel’nikov S.A., Pavel’ev D.I., 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://journal.microbe.ru/jour/article/view/2040

Отмена обязательного оспопрививания привела к падению коллективного иммунитета, и человечество стало уязвимым к таким давно известным инфекциям, как оспа обезьян (mpox), коров, буйволов, верблюдов и вновь появившимся, вызываемым вирусами Аляска и Ахмета. Поэтому необходимы безопасные оспенные вакцины, иммуногенность которых сравнима с иммуногенностью вакцин, применяемых в период ликвидации натуральной оспы. Цель обзора – анализ исследований японских ученых по получению и изучению свойств противооспенной вакцины LC16m8 и оценка дальнейших перспектив применения штамма LC16m8. На основе одного из клонов Lister получена вакцина LC16m8, которая лицензирована в Японии с 1975 г. При полногеномном секвенировании выявлено, что основным ее отличием от генома исходного штамма является мутация в гене B5R, которая определяет его безопасность для лабораторных животных и человека. Иммуногенность вакцины на основе штамма сопоставима с иммуногенностью вакцин I поколения: Lister, Dryvax, Ikeda. По рекомендации ВОЗ вакцины II поколения АСАМ 2000 и III поколения на основе штамма LC16m8 являются препаратами резерва. Однако установленная способность штамма LC16m8 при пассировании в культуре клеток спонтанно ревертировать к исходному варианту штамма Lister обусловила проведение генно-инженерных работ по делетированию гена B5R для получения мутанта LC16m8Δ, не способного к реверсии. Вакцина на основе штамма LC16m8Δ формально могла бы быть отнесена к препаратам IV поколения, а с учетом высокой иммуногенности и относительной безопасности этого штамма по результатам доклинических исследований возможна реальная перспектива получения на его основе современного и эффективного препарата резерва. Таким образом, анализ многолетних данных по изучению вакцины LC16m8 свидетельствует о том, что данный препарат по показателям эффективности и безопасности превосходит другие аналоги I, II и III поколений. Дальнейшие генно-инженерные работы с этим штаммом, позволившие получить безопасный, но иммуногенный геновариант штамма LC16m8Δ, – наглядный пример продуктивного движения к разработке безопасных и эффективных вакцин IV поколения.

Abrogation of obligatory vaccination against smallpox has lead to degradation of herd immunity and humanity has become vulnerable to long known infections, such as monkeypox (mpox), cowpox, camelpox, buffalopox and emerging ones, caused by viruses Alaska and Akhmeta. This situation demands availability of safe smallpox vaccines, the immunogenicity of which is comparable to vaccines used in the period of smallpox elimination. The aim of this review is to analyze the research of Japanese scientists on the production and investigation of properties of the smallpox vaccine LC16m8 and to assess further prospects for the use of the LC16m8 strain. The LC16m8 vaccine was obtained based on one of the Lister clones and has been licensed in Japan since 1975. Whole-genome sequencing revealed that its main difference from the genome of the original strain is a mutation in the B5R gene, which determines its safety for laboratory animals and humans. The immunogenicity of the vaccine based on this strain is comparable to the immunogenicity of the first generation vaccines: Lister, Dryvax, Ikeda. According to WHO recommendations, second generation vaccines ACAM 2000 and third generation vaccines based on the LC16m8 strain are reserve drugs. However, the established fact that the LC16m8 strain, when passaged in cell culture, spontaneously reverts to the original variant of the Lister strain led to genetic engineering work to delete the B5R gene to obtain the LC16m8Δ mutant, which is not capable of reversion. A vaccine based on the LC16m8Δ strain could technically be classified as a fourth generation drug, and taking into account the high immunogenicity and relative safety of this strain based on the results of preclinical studies, there is a real prospect of producing an advanced and effective reserve drug based on it. Thus, analysis of long-term data on the study of the LC16m8 vaccine indicates that this drug is superior to other analogues of the 1st, 2nd and 3rd generation in terms of effectiveness and safety. Further genetic engineering work with this strain, which made it possible to obtain a safe but immunogenic genovariant of the LC16m8Δ strain, is a clear example of a productive movement towards the development of safe and effective fourth generation vaccines.

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