epidemiologyЭпидемиология и ВакцинопрофилактикаEpidemiology and Vaccinal Prevention2073-30462619-0494«Numicom» LLC10.31631/2073-3046-2017-16-3-65-70epidemiology-278Research ArticleОФИЦИАЛЬНАЯ ИНФОРМАЦИЯOFFICIAL INFORMATIONУсиление эффективности кандидатной вакцины против гриппа сочетанием консервативных последовательностей гемагглютинина и М2 белкаStrengthening the Effectiveness of the Candidate Influenza Vaccine by Combining Conserved Sequences of Hemagglutinin and M2 proteinЦыбаловаЛ. М.TsybalovaL. M.sovet@influenza.spb.ruСтепановаЛ. А.StepanovaL. A.noemail@neicon.ruКотляровР. Ю.KotlyarovR. Yu.noemail@neicon.ruБлохинаЕ. А.BlokhinaE. A.noemail@neicon.ruШуклинаМ. А.ShuklinaM. A.noemail@neicon.ruМардановаЕ. С.MardanovaE. S.noemail@neicon.ruКоротковА. В.KorotkovA. V.noemail@neicon.ruПотапчукМ. В.PotapchukM. V.noemail@neicon.ruРавинН. В.RavinN. V.noemail@neicon.ruФГБУ «НИИ гриппа» Минздрава РоссииРоссияFederal State Budget Institution Research «Institute of Influenza» of the Ministry of Healthcare of the Russian FederationRussian FederationФГУ «ФИЦ «Фундаментальные основы биотехнологии» РАНРоссияFederal State Institution «The Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of SciencesRussian Federation2017200620171636570Copyright © Цыбалова Л.М., Степанова Л.А., Котляров Р.Ю., Блохина Е.А., Шуклина М.А., Марданова Е.С., Коротков А.В., Потапчук М.В., Равин Н.В., 20172017Цыбалова Л.М., Степанова Л.А., Котляров Р.Ю., Блохина Е.А., Шуклина М.А., Марданова Е.С., Коротков А.В., Потапчук М.В., Равин Н.В.Tsybalova L.M., Stepanova L.A., Kotlyarov R.Y., Blokhina E.A., Shuklina M.A., Mardanova E.S., Korotkov A.V., Potapchuk M.V., Ravin N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.epidemvac.ru/jour/article/view/278

Разработка универсальной вакцины против гриппа - вакцины, направленной на все субтипы вирусов гриппа человека, - является наиболее актуальной современной задачей в специфической профилактике гриппа. В настоящей статье дана сравнительная характеристика специфической активности нескольких вариантов рекомбинантного вакцинного белка, включающего антигенные детерминанты вируса гриппа - эктодомен белка М2 (М2е) и фрагмент второй субъединицы гемагглютинина (аминокислотная последовательность 76 -130). В качестве белка-носителя и адъюванта был выбран флагеллин - белок Salmonella typhimurium как полноразмерный, так и с делетированной гипервариабельной частью. На экспериментальных животных показана высокая иммуногенность препаратов и способность предотвращать летальность при инфицированнии вирусом гриппа. Наибольшей протективностью обладал гибридный белок Flg-HA2-4M2 - полноразмерный флагеллин с НА2 (76 - 130) и М2е на С-конце. Препарат обеспечивал 100% выживаемость при заражении высокой дозой вируса гриппа A(H3N2) - 10 LD50. Белки, содержащие только полноразмерный флагеллин с М2е или укороченную форму флагеллина с М2е на С-конце и с НА2 в гипервариабельном участке, защищали 75% животных от летальной инфекции. Белок Flg-HA2-4M2 перспективен для дальнейшего исследования в качестве вакцины.

The development of universal influenza vaccine - a vaccine directed to all subtypes of human influenza A viruses - is the really actual problem task. This paper presents the comparative characteristic of the specific activity of various recombinant proteins consisting of antigenic determinants of influenza A virus - the ectodomain of the M2 protein (M2e) and a fragment of the second subunit of the hemagglutinin (the amino acid sequence 76 - 130). Flagellin - Salmonella typhimurium protein was used as carrier protein and as adjuvant. We use two forms of flagellin: full size and with deleted hypervariable region. The proteins showed high immunogenicity, and the ability to prevent lethal infection of influenza virus in mice. Full-length flagellin with HA2 (76 - 130) and M2e on the C-terminus (protein Flg-HA2-4M2e) demonstrated the most protective properties. It provides 100% survival immunized mice that were challenge with a high dose of influenza A (H3N2) - 10 LD50. Proteins containing only full sized flagellin with M2e or flagellin truncated form with M2e at the C-terminus and HA2 within the hypervariable region, protected 75% of animals from lethal infection. Protein Flg-HA2-4M2e is promising for further study as a vaccine.

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