Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1763610.15789/2220-7619-POD-17636REVIEWSОБЗОРЫReview ArticleProspectives of developing therapeutic HPV vaccinesПерспективы разработки терапевтических вакцин против папилломавирусной инфекцииRaevskayaNatalja M.РаевскаяНаталья Михайловна
Russian Federation

PhD (Biology), Expert of the Allergens, Cytokines and Other Immunomodulators Department, Centre for Biological Medicinal Products Evaluation and Control

к.б.н., эксперт управления аллергенов, цитокинов и других иммуномодуляторов Центра экспертизы и контроля МИБП

raevskayanm@expmed.ruNikitinaT. N.НикитинаТ. Н.
Russian Federation

PhD (Medicine), Head Expert of the Allergens, Cytokines and Other Immunomodulators Department, Centre for Biological Medicinal Products Evaluation and Control

к.м.н., главный эксперт управления аллергенов, цитокинов и других иммуномодуляторов Центра экспертизы и контроля МИБП

raevskayanm@expmed.ruSimbirtsevA. S.СимбирцевА. С.
Russian Federation

RAS Corresponding Member, DSc (Medicine), Professor, Head Researcher

член-корреспондент РАН, д.м.н., профессор, главный научный сотрудник

raevskayanm@expmed.ruSolovyevaI. L.СоловьеваИ. Л.
Russian Federation

DSc (Medicine), Professor, Head of the Department of Pediatrics, Faculty of Medicine named after T.Z. Biktimirov, Institute of Medicine, Ecology and Physical Education

д.м.н., профессор, зав. кафедрой педиатрии медицинского факультета им. Т.З. Биктимирова Института медицины, экологии и физической культуры

raevskayanm@expmed.ruVolginA. R.ВолгинА. Р.
Russian Federation

PhD (Medicine), Deputy Director, Centre for Biological Medicinal Products Evaluation and Control

к.м.н., зам. директора Центра экспертизы и контроля МИБП

raevskayanm@expmed.ruKorovkinA. S.КоровкинА. С.
Russian Federation

PhD (Medicine), Director of the Centre for Biological Medicinal Products Evaluation and Control

к.м.н., директор Центра экспертизы и контроля МИБП

raevskayanm@expmed.ruScientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of the Russian FederationФГБУ Научный центр экспертизы средств медицинского применения Минздрава РоссииState Research Institute of Highly Pure Biopreparations FMBAФГУП Государственный научно-исследовательский институт особо чистых биопрепаратов ФМБАUlyanovsk State UniversityФГБОУ ВО Ульяновский государственный университет11062024311020241446556710904202415052024Copyright ©; 2024, Raevskaya N.M., Nikitina T.N., Simbirtsev A.S., Solovyeva I.L., Volgin A.R., Korovkin A.S.Copyright ©; 2024, Раевская Н.М., Никитина Т.Н., Симбирцев А.С., Соловьева И.Л., Волгин А.Р., Коровкин А.С.2024Raevskaya N.M., Nikitina T.N., Simbirtsev A.S., Solovyeva I.L., Volgin A.R., Korovkin A.S.Раевская Н.М., Никитина Т.Н., Симбирцев А.С., Соловьева И.Л., Волгин А.Р., Коровкин А.С.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/17636

Human papillomavirus (HPV) represents one of the most serious global public health problems. Malignant female and male diseases mainly result from persistent HPV infection. Cancer belongs to a high mortality rate disease. It has been established that HPV infection causes about 70% vaginal cancer, 50% male genital cancer, 90% anal cancer and 60% head-and-neck cancer. Annually, a large number of people develop various HPV-caused cancer types, dominated by cervical cancer, one of the most common and aggressive types of cancer that threatens health holding the fourth place among most female common cancer worldwide. According to the World Health Organization (WHO), in 2020, about 600 cases of cervical cancer are recorded daily in different countries. Emergence of cervical cancer is closely related to factors such as long-term (persistent) HPV infection and somatic mutations of the host genome. Although HPV infection can be detected and cured early with highly effective screening methods and surgical procedures, the carcinogenic risk of HPV related diseases constantly increases, which elimination faces certain difficulties, especially in low- and mid-developed countries. The most acceptable solution to this is development and implementation of therapeutic vaccines for prevention and treatment of HPV related diseases. Three licensed HPV vaccines based on L1 type virus-like particles (L1-VLPs) technology are available globally: bivalent (HPV-2), quadrivalent (HPV-4) and nonavalent (HPV-9) vaccines. These vaccines demonstrated effectiveness in reducing HPV-related cervical cancer rate by up to 90% worldwide. However, the therapeutic effect of these vaccines on persistent HPV infection and lesions has not been observed. Therapeutic HPV vaccines candidates targeted Ye6/Ye7 cancer proteins activate cellular immunity that eliminates existing HPV infection. Here we review types, mechanisms of action and clinical effects of therapeutic HPV vaccines, as well as current and future developments in the field for prevention and treatment of HPV related diseases.

Вирус папилломы человека (ВПЧ) является одной из серьезных проблем общественного здравоохранения. Длительно существующая ВПЧ-инфекция является главной причиной возникновения злокачественных заболеваний у мужчин и женщин. Рак относится к заболеваниям с высоким уровнем смертности. Установлено, что ВПЧ-инфекция примерно на 70% связана с раком влагалища, на 50% — с раком половых органов у мужчин, на 90% — с раком анального канала и 60% — c раком головы. Ежегодно у большого количества людей развиваются разные виды рака, инициированные ВПЧ, ведущим из которых является рак шейки матки. Рак шейки матки — один из наиболее распространенных и агрессивных видов рака, угрожающих здоровью, является четвертым по распространенности в мире раком у женщин. По данным Всемирной организации здравоохранения (ВОЗ), на 2020 г. около 600 случаев заболеваемости раком шейки матки регистрируется ежедневно в различных странах мира. Возникновение рака шейки матки тесно связано с такими факторами, как длительно существующая (персистирующая) инфекция ВПЧ и соматические мутации генома хозяина. Несмотря на то что поражения, вызванные ВПЧ могут быть выявлены и удалены на ранней стадии с помощью высокоэффективных методов скрининга и хирургических процедур, канцерогенный риск, вызванный ВПЧ-инфекцией продолжает увеличиваться, и есть определенные сложности в ее устранении, особенно в странах с низким уровнем развития. Решением данного вопроса является создание терапевтических вакцин как на этапах профилактики, так и лечения. На сегодняшний день существует три лицензированные профилактические вакцины против ВПЧ на основе вирусоподобных частиц типа L1 (L1-VLP): бивалентная (ВПЧ-2), четырехвалентная (ВПЧ-4) и нонавалентная (ВПЧ-9) вакцины. Использование этих вакцин позволило эффективно устранить около 90% случаев инфицирования ВПЧ во всем мире. Однако терапевтического эффекта данных вакцин в отношении персистирующей ВПЧ-инфекции и вызванных ею поражений замечено не было. Особенностью терапевтических вакцин, разрабатываемых для онкобелков Е6/Е7, является активация клеточного иммунитета, что считается идеальным иммунным способом устранения вирусной инфекции. В представленном обзоре приведена информация, касающаяся классификации, механизма действия и клинических эффектов вакцин против ВПЧ, а также разработки и перспективных направлений в отношении терапевтических вакцин, используемых для профилактики и лечения злокачественных заболеваний.

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