mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2016-5-425-436mimmun-1066Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESРЕЗУЛЬТАТЫ ПИЛОТНОГО КЛИНИЧЕСКОГО ИССЛЕДОВАНИЯ ВАКЦИН НА ОСНОВЕ ДЕНДРИТНЫХ КЛЕТОК В ЛЕЧЕНИИ РЕЦИДИВИРУЮЩЕЙ ГЕРПЕСВИРУСНОЙ ИНФЕКЦИИRESULTS OF A PILOT CLINICAL TRIAL OF DENDRITICCELL BASED VACCINES FOR TREATMENT OF RECURRENT HERPESVIRUS INFECTIONЛеплинаО. Ю.LeplinaO. Yu.

д.м.н., ведущий научный сотрудник, лаборатория клеточной иммунотерапии,

630099, г. Новосибирск, ул. Ядринцевская, 14,

ct_lab@mail.ru

PhD, MD (Medicine), Leading Research Associate, Laboratory of Cellular Immunotherapy,

630099, Novosibirsk, Yadrintsevskaya str., 14

oleplina@mail.ruСтаростинаН. М.StarostinaN. M.

к.м.н., заслуженный врач РФ, заведующая отделением иммунологии клиники иммунопатологии,

г. Новосибирск

PhD (Medicine), Honored Doctor of the Russian Federation, Head, Department of Immunology, Clinics of Immunopathology,

Novosibirsk

БлиноваД. Д.BlinovaD. D.

врач-иммунолог отделения иммунологии клиники иммунопатологии,

г. Новосибирск

Doctor (Immunology), Department of Immunology, Clinics of Immunopathology,

Novosibirsk

ЖелтоваО. И.ZheltovaO. I.

к.м.н., врач-иммунолог отделения иммунологии клиники иммунопатологии,

г. Новосибирск

PhD (Medicine), Doctor (Immunology), Department of Immunology, Clinics of Immunopathology,

Novosibirsk

ОлейникЕ. А.OleinikE. A.

аспирант, лаборатория клеточной иммунотерапии,

г. Новосибирск

Postdoc Fellow, Laboratory of Cellular Immunotherapy,

Novosibirsk

ТыриноваТ. В.TyrinovaT. V.

к.м.н., научный сотрудник лаборатории клеточной иммунотерапии,

г. Новосибирск

PhD (Medicine), Research Associate, Laboratory of Cellular Immunotherapy,

Novosibirsk

ОстанинА. А.OstaninA. A.

д.м.н., профессор, главный научный сотрудник лаборатории клеточной иммунотерапии,

г. Новосибирск

PhD, MD (Medicine), Professor, Main Research Associate, Laboratory of Cellular Immunotherapy,

Novosibirsk

ЧерныхЕ. Р.ChernykhE. R.

д.м.н., профессор, член-корр. РАН, заведующая лабораторией клеточной иммунотерапии,

г. Новосибирск

PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Head, Laboratory of Cellular Immunotherapy,

Novosibirsk

ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии»РоссияResearch Institute of Fundamental and Clinical ImmunologyRussian Federation201624082016185425436Copyright © Леплина О.Ю., Старостина Н.М., Блинова Д.Д., Желтова О.И., Олейник Е.А., Тыринова Т.В., Останин А.А., Черных Е.Р., 20162016Леплина О.Ю., Старостина Н.М., Блинова Д.Д., Желтова О.И., Олейник Е.А., Тыринова Т.В., Останин А.А., Черных Е.Р.Leplina O.Y., Starostina N.M., Blinova D.D., Zheltova O.I., Oleinik E.A., Tyrinova T.V., Ostanin A.A., Chernykh E.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.mimmun.ru/mimmun/article/view/1066

Хроническое рецидивирующее течение инфекции, обусловленной вирусами простого герпеса (ВПГ) 1 и 2 типа, представляет серьезную медико-социальную проблему. Учитывая важную роль иммунной системы в контроле за вирусом, перспективы лечения рецидивирующих форм ВПГ-инфекции связывают с активацией антигенспецифического иммунного ответа, в частности с использованием вакцин на основе дендритных клеток (ДК). В настоящей работе представлены результаты открытого пилотного исследования эффективности и безопасности дендритноклеточных вакцин у пациентов с рецидивирующей ВПГ-инфекцией. В исследование были включены 29 человек, включая 14 пациентов с лабиальным и 15 с генитальным герпесом. ДК генерировали в присутствии GM-CSF и IFNα, нагружали рекомбинантными вирусными белками (HSV1gD или HSV-2gD) и проводили 2 курса вакцинаций в течение 9 мес. Иммунотерапия ДК не вызывала серьезных нежелательных эффектов и сопровождалась более чем двукратным снижением частоты рецидивов и увеличением длительности ремиссии на фоне 9 мес. лечения. В период последующего 6-месячного периода наблюдалось дальнейшее снижение частоты рецидивов и трехкратное возрастание длительности ремиссии. Клинический эффект на фоне лечения и в период 6 мес. наблюдения отмечался как в группе с лабиальным, так и генитальным герпесом, регистрировался у большинства пациентов, ассоциировался с индукцией антигенспецифического пролиферативного ответа и нормализацией исходно сниженной митогенной реактивности мононуклеарных клеток в ответ на стимуляцию КонА. Анализ отдаленных результатов лечения на основе анкетирования пациентов с давностью наблюдения более 24 мес. показал, что положительный эффект иммунотерапии в виде снижения частоты рецидивов через 48 мес. (медиана наблюдения) сохранялся у 77,8% опрошенных. Антигенспецифический пролиферативный ответ в эти сроки сохранялся у 66,7%. Полученные результаты позволяют рассматривать ДК-вакцины в качестве нового перспективного подхода к лечению рецидивирующих форм лабиального и генитального герпеса.

Chronic recurrent infections caused by herpes simplex virus (HSV) types 1 and 2 represent a serious medical and social challenge. Given an important role of immune system in surveillance of viral infections, an induced enhancement of antigen-specific immune response seems to be a promising approach to treatment of recurrent HSV infections, in particular, using dendritic cell (DCs) vaccines. The present paper contains results of an open pilot study evaluating efficacy and safety of dendritic-cell vaccines in the patients with recurrent HSV infections. Twenty-nine patients including 14 persons with labial herpes, and 15, with genital herpes have been enrolled in this study. DCs were generated in presence of GM-CSF and IFNα and then loaded with recombinant viral proteins (HSV1gD or HSV2gD). These cells were applied in 2 rounds of vaccination performed within 9 months. Immunotherapy with DCs did not induce sufficient side effects, and was accompanied by more than two-fold decrease in relapse rate and increased length of remissions during the 9-month period of treatment. Later on, we revealed a reduced frequency of relapses, and a 3-fold increase in remission duration over the subsequent 6-month follow up. The clinical effect during the treatment and at later terms (a half-year observation) was noted with both labial and genital herpes, as registered in the majority of patients, being associated with induction of antigen-specific proliferative response and normalization of reduced mitogenic responsiveness of mononuclear cells towards ConA. The patients’ survey at longer terms (more than 24 months) has shown that the beneficial effect of immunotherapy, in terms of reduced relapse rates, was maintained in 77.8% of the respondents by 48 months (a median follow-up term). At this time, the antigen specific proliferative response was maintained in 66.7% of patients. The data obtained suggest that the dendritic-cell vaccines may be a promising approach to the treatment of recurrent labial and genital herpes.

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