biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Products10.30895/2221-996X-2024-24-3-243-254biopreparat-589Research ArticleТЕМА НОМЕРА: РАЗРАБОТКА ДИАГНОСТИЧЕСКИХ, ЛЕЧЕБНЫХ И ПРОФИЛАКТИЧЕСКИХ ПРЕПАРАТОВ ПРОТИВОВИРУСНОГО ДЕЙСТВИЯISSUE TOPIC: DEVELOPMENT OF MEDICINAL PRODUCTS FOR DIAGNOSIS, TREATMENT, AND PREVENTION OF VIRAL INFECTIONSВакцины против вируса папилломы человека: организация и опыт проведения доклинических исследованийHuman papillomavirus vaccines: organisation and experience of preclinical studieshttps://orcid.org/0000-0002-3241-1053КоровкинА. С.KorovkinA. S.

Коровкин Алексей Сергеевич, канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Alexey S. Korovkin, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

korovkinas@expmed.ruhttps://orcid.org/0000-0001-9344-5655НикитинаТ. Н.NikitinaT. N.

Никитина Татьяна Николаевна, канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Tatiana N. Nikitina, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

nikitina@expmed.ruhttps://orcid.org/0000-0003-0819-2978КозловаТ. Ю.KozlovaT. Yu.

Козлова Татьяна Юрьевна

Петровский б-р, д. 8, стр. 2, Москва, 127051

Tatiana Yu. Kozlova

8/2 Petrovsky Blvd, Moscow 127051

kozlovatu@expmed.ruhttps://orcid.org/0000-0003-0940-8080ГоренковД. В.GorenkovD. V.

Горенков Дмитрий Витальевич

Петровский б-р, д. 8, стр. 2, Москва, 127051

Dmitry V. Gorenkov

8/2 Petrovsky Blvd, Moscow 127051

gorenkov@expmed.ruhttps://orcid.org/0000-0002-8097-2680ВолгинА. Р.VolginA. R.

Волгин Андрей Рудольфович, канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Andrey R. Volgin, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

volgin@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202403102024243Разработка диагностических, лечебных и профилактических препаратов противовирусного действия243254Copyright © Коровкин А.С., Никитина Т.Н., Козлова Т.Ю., Горенков Д.В., Волгин А.Р., 20242024Коровкин А.С., Никитина Т.Н., Козлова Т.Ю., Горенков Д.В., Волгин А.Р.Korovkin A.S., Nikitina T.N., Kozlova T.Y., Gorenkov D.V., Volgin A.R.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/589ВВЕДЕНИЕ

ВВЕДЕНИЕ. Основным мероприятием в первичной профилактике заболеваний, вызываемых вирусом папилломы человека (ВПЧ), является вакцинация. Разработка новых вакцин-кандидатов ведется во всем мире, в том числе и в Российской Федерации. В то же время серьезной проблемой на пути к внедрению новых ВПЧ-вакцин в практику здравоохранения является отсутствие четких и однозначных рекомендаций по проведению их доклинических исследований (ДКИ).

ЦЕЛЬ

ЦЕЛЬ. Анализ нормативных документов, изучение опыта проведения ДКИ ВПЧ-вакцин и обобщение подходов к ДКИ, которые могут быть рекомендованы разработчикам и заявителям при регистрации новых вакцин для профилактики папилломавирусной инфекции, в том числе разрабатываемых в Российской Федерации.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Изучены как нормативные правовые документы ВОЗ, ICH, ЕЭК, так и результаты экспериментальной части в рамках проведения ДКИ ВПЧ-вакцин. Зарегистрированные и разрабатываемые ВПЧ-вакцины схожи по своим характеристикам и конструктивным особенностям, но могут различаться по спектру перекрываемых серотипов и методам получения капсидного белка L1 ВПЧ. В настоящее время подтверждена роль белка L1 в формировании специфического протективного иммунитета, поэтому отсутствует необходимость проведения тестов заражения с использованием животных моделей. Моделирование папилломатоза может потребоваться при выборе альтернативных иммунологических мишеней или при изучении иного пути введения вакцины, отличного от парентерального. В программу ДКИ могут быть включены отдельные этапы по проведению комплексной оценки новых адъювантов и иных дополнительных компонентов в составе новых ВПЧ-вакцин.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. На основании изучения международного опыта систематизированы методы и подходы к проведению ДКИ ВПЧ-вакцин. Сформулированы рекомендации для разработчиков ВПЧ-вакцин по планированию и организации ДКИ, включая изучение иммуногенности, токсикологических свойств, местной переносимости, необходимых для государственной регистрации новых препаратов.

INTRODUCTION

INTRODUCTION. Vaccination is the main measure for the primary prevention of human papillomavirus (HPV)-related diseases. The development of novel vaccine candidates is underway worldwide, including in the Russian Federation. At the same time, the clinical introduction of new HPV vaccines is seriously hampered by the lack of clear and unambiguous recommendations for conducting preclinical studies of these vaccines.

AIM

AIM. This study aimed to analyse regulatory documents on HPV vaccines, to study the experience of conducting preclinical studies, and to summarise the preclinical approaches that could be recommended for developers and applicants seeking approval for new preventive HPV vaccines, including the vaccines being developed in the Russian Federation.

DISCUSSION

DISCUSSION. The authors have analysed regulatory documents issued by the World Health Organisation (WHO), the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), and the Council of the Eurasian Economic Commission (EEC). Additionally, the authors have reviewed the experimental results of preclinical studies of HPV vaccines. The known licensed and pipeline HPV vaccines are similar in terms of their characteristics and constructive features. However, there may be some differences in the HPV serotype coverage and the methods used to produce the HPV L1 capsid protein. To date, studies have confirmed the role of the HPV L1 capsid protein in the development of specific immunity, rendering challenge tests in animal models unnecessary. Papillomatosis modelling may be required for choosing an alternative immunological target or for studying an alternative (non-parenteral) route for vaccine administration. Preclinical study programmes may be supplemented with individual stages of comprehensive assessment of adjuvants and other additives included in novel HPV vaccine compositions.

CONCLUSIONS

CONCLUSIONS. The authors have studied the international experience and presented a systemic overview of the methods and approaches used in preclinical studies of HPV vaccines. The authors have formulated recommendations for developers for the planning and organisation of preclinical studies of HPV vaccines (including immunogenicity, toxicity, and local tolerance assessments required for licensing new vaccines).

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