microbeПроблемы особо опасных инфекцийProblems of Particularly Dangerous Infections0370-10692658-719XRussian Research Anti-Plague Institute “Microbe”10.21055/0370-1069-2019-2-37-44microbe-1146Research ArticleОБЗОРЫREVIEWSАнализ и перспективы применения рекомбинантного вируса вакцины, штамм MVA, в качестве вектора при разработке вакцин против заболеваний, вызванных вирусами иммунодефицита человека и обезьянAnalysis and Prospects of Using Recombinant Vaccinia Virus MVA Strain as a Vector in the Development of the Vaccines against Human and Simian Immunodeficiency Virus DiseasesСтовбаЛ. Ф.StovbaL. F.

Сергиев Посад

Sergiev Possad

48cnii@mil.ruКротковВ. Т.KrotkovV. T.

Сергиев Посад

Sergiev Possad

48cnii@mil.ruПавельевД. И.Paveli’evD. I.

Сергиев Посад

Sergiev Possad

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

Сергиев Посад

Sergiev Possad

48cnii@mil.ruЛебедевВ. Н.LebedevV. N.

Сергиев Посад

Sergiev Possad

48cnii@mil.ruБорисевичС. В.BorisevichS. V.

Сергиев Посад

Sergiev Possad

48cnii@mil.ruФГБУ «48 Центральный научно-исследовательский институт» Министерства обороны Российской ФедерацииРоссия48th Central Research Institute» of the Ministry of Defense of the Russian FederationRussian Federation201901072019023744Copyright © Стовба Л.Ф., Кротков В.Т., Павельев Д.И., Мельников С.А., Лебедев В.Н., Борисевич С.В., 20192019Стовба Л.Ф., Кротков В.Т., Павельев Д.И., Мельников С.А., Лебедев В.Н., Борисевич С.В.Stovba L.F., Krotkov V.T., Paveli’ev D.I., Mel’nikov S.A., Lebedev V.N., 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/1146

В обзоре представлены результаты доклинического применения векторных вакцин против заболеваний, вызванных вирусами иммунодефицита человека и иммунодефицита обезьян. Использование только антиретровирусной терапии является недостаточным для элиминации ВИЧ из организма больного. Это обстоятельство диктует необходимость получения эффективной вакцины, которая позволит сократить количество новых случаев заболевания и уменьшит риск трансмиссии вируса. Существующая практика создания медицинских средств защиты показала эффективность режимов гетерологичного праймирования/бустирования для формирования выраженного иммунного ответа у лабораторных животных. В качестве праймирующих вакцин использовали различные векторные конструкции: ДНК-вакцины, вакцина Кальметта-Герена (BCG), аденовирус шимпанзе, вирус везикулярного стоматита, альфавирусный репликлон. Бустерная вакцина представлена рекомбинантным вирусом вакцины, штамм MVA. Во все векторные вакцины встраивались разнообразные гены иммунодоминантных антигенов возбудителей иммунодефицита человека и иммунодефицита обезьян. На макаках-резусах, кроликах и мышах показано, что применяемые схемы вакцинации были безопасны и формировали иммунный ответ. Поскольку оболочечный белок ВИЧ высоко вариабелен, сильно гликозилирован и подвергается структурным изменениям при рецепторном связывании, он не может служить мишенью для индукции вируснейтрализующих антител. Поэтому в проведенных исследованиях, в основном, изучали клеточный иммунный ответ, который представлен полифункциональными CD8+ Т-клетками. Однако ряд исследований последних лет направлен на такую модификацию оболочечного иммуногена ВИЧ, которая будет способствовать индукции вируснейтрализующих антител. Проведенное изучение защитной эффективности индуцированного иммунитета на макаках-резусах, иммунизированных рекомбинантными векторами, экспрессирующими иммунодоминантные антигены ВИО, при последующем заражении их вирулентным штаммом ВИО, выявило, что все обезьяны заболевали. С учетом того, что конструкции с иммунодоминантными антигенами ВИО, при проведении оценки их защитной эффективности на макаках-резусах имитируют СПИД у человека, то, вероятно, что разработанные к настоящему времени вакцины не будут эффективными при формировании коллективного иммунитета против СПИДа. Поэтому в настоящее время приоритетным направлением исследований продолжает оставаться поиск новых сочетаний экспессируемых иммунодоминантных антигенов в праймирующие и бустерные вакцины.

The review presents the results of preclinical use of vector vaccines against human immunodeficiency virus (HIV) disease and simian immunodeficiency virus (SIV) disease. Application of antiretroviral therapy exclusively is insufficient for elimination of HIV from patient’s body. This dictates the need for an effective vaccine which will reduce the number of new cases of the disease and reduce the risk of virus transmission. Current practice of medicinal product development showed the effectiveness of heterologous prime-boost regimens for the induction of expressed immune response in laboratory animals. Various vector constructs were used as priming vaccines: DNA vaccines, Bacille Calmette-Guerin vaccine, chimpanzee adenovirus, vesicular stomatitis virus, alphavirus repli-clone. Booster vaccine was represented by recombinant MVA strain. In all vector vaccines, different genes of immunodominant antigens of HIV and SIV agents were inserted. On rhesus macaques, murine, rabbit models, it was demonstrated that deployed vaccination schemes were safe and induced immune response. Because membrane HIV protein is highly variable, strongly glycoziled and subjected to structural changes during receptor binding, it cannot be viewed as a target for induction of virus neutralized antibodies. Therefore, we mainly studied the cell immune response that was presented by poly-functional CD8+ T-cells. However, some recent researches are aimed at such modification of envelope HIV immunogene that would provide for virus neutralizing antibody induction. The study of protective efficiency of the induced immunity in rhesus macaques, immunized with recombinant vectors expressing SIV’ s immunodominant antigens, in case of subsequent inoculation with virulent SIV strain has revealed that all monkeys developed illness. Assuming that the constructions with SIV’ s immunodominant antigens under protective efficiency testing on rhesus macaques imitate AIDS in humans, it seems that vaccines, developed up-to-date, will not be effective for collective immunity formation against AIDS. Therefore, the search for novel combinations of expressed immunodominant antigens for the inclusion into the composition of priming and booster vaccines remains a priority area at present time.

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