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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">mimmun</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинская иммунология</journal-title><trans-title-group xml:lang="en"><trans-title>Medical Immunology (Russia)</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1563-0625</issn><issn pub-type="epub">2313-741X</issn><publisher><publisher-name>SPb RAACI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15789/1563-0625-2016-6-545-554</article-id><article-id custom-type="elpub" pub-id-type="custom">mimmun-1135</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group></article-categories><title-group><article-title>ИСПОЛЬЗОВАНИЕ ЛАКТОБАЦИЛЛ В КАЧЕСТВЕ АДЪЮВАНТОВ ПРИ ИНТРАНАЗАЛЬНОЙ ИММУНИЗАЦИИ ХИМЕРНОЙ ПНЕВМОКОККОВОЙ ВАКЦИНОЙ</article-title><trans-title-group xml:lang="en"><trans-title>EVALUATION OF LACTOBACILLUS PROBIOTICS AS ADJUVANTS FOR NASAL IMMUNIZATION WITH CHIMERIC PNEUMOCOCCAL VACCINE</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Леонтьева</surname><given-names>Г. Ф.</given-names></name><name name-style="western" xml:lang="en"><surname>Leontieva</surname><given-names>G. F.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.б.н., ведущий научный сотрудник отдела молекулярной микробиологии</p></bio><bio xml:lang="en"><p>PhD (Biology), Leading Research Associate</p></bio><email xlink:type="simple">galeonte@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Крамская</surname><given-names>Т. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kramskaya</surname><given-names>T. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.б.н., старший научный сотрудник отдела молекулярной микробиологии</p></bio><bio xml:lang="en"><p>PhD (Biology),Senior Research Associate</p></bio><email xlink:type="simple">galeonte@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Грабовская</surname><given-names>К. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Grabovskaya</surname><given-names>K. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., старший научный сотрудник отдела молекулярной микробиологии</p></bio><bio xml:lang="en"><p>PhD (Medicine), Senior Research Associate</p></bio><email xlink:type="simple">galeonte@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Филимонова</surname><given-names>В. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Filimonova</surname><given-names>V. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>научный сотрудник отдела молекулярной микробиологии</p></bio><bio xml:lang="en"><p>Research Associate</p></bio><email xlink:type="simple">galeonte@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лайно</surname><given-names>Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Laiñ o</surname><given-names>J.</given-names></name></name-alternatives><bio xml:lang="ru"><p>научный сотрудник лаборатории иммунобиотехнологии</p></bio><bio xml:lang="en"><p>Research Associate, Laboratory of Immunobiotechnology</p></bio><email xlink:type="simple">galeonte@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Виллена</surname><given-names>Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Villena</surname><given-names>J.</given-names></name></name-alternatives><bio xml:lang="ru"><p>профессор, руководитель лаборатории иммунобиотехнологии</p></bio><bio xml:lang="en"><p>Professor, Head, Laboratory of Immunobiotechnology</p></bio><email xlink:type="simple">galeonte@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Альварес</surname><given-names>С.</given-names></name><name name-style="western" xml:lang="en"><surname>Alvares</surname><given-names>S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>научный сотрудник лаборатории иммунобиотехнологии</p></bio><bio xml:lang="en"><p>Research Associate, Laboratory of Immunobiotechnology</p></bio><email xlink:type="simple">galeonte@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Даниленко</surname><given-names>В. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Danilenko</surname><given-names>V. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.б.н., профессор, заведующий отделом генетических основ биотехнологии</p></bio><bio xml:lang="en"><p>PhD, MD (Biology), Head, Division of Fundamental Genetic Studies in Biotechnology</p></bio><email xlink:type="simple">galeonte@yandex.ru</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Суворов</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Suvorov</surname><given-names>A. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.м.н., профессор, заведующий отделом молекулярной микробиологии, заведующий кафедрой фундаментальных проблем медицины и медицинской технологии</p></bio><bio xml:lang="en"><p>PhD, MD (Medicine), Head, Division of Molecular Microbiology</p></bio><email xlink:type="simple">galeonte@yandex.ru</email><xref ref-type="aff" rid="aff-4"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «Институт экспериментальной медицины», Санкт-Петербург, Россия</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Institute of Experimental Medicine, St. Petersburg, Russian Federation</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Референсный центр по исследованию лактобацилл, Тукуман, Аргентина</institution><country>Аргентина</country></aff><aff xml:lang="en"><institution>Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina</institution><country>Argentina</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБУН «Институт общей генетики им. Н.И. Вавилова» РАН, Москва, Россия</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Institute of General Genetics, Russian Academy of Sciences, Moscow, Russian Federation</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>ФГБНУ «Институт экспериментальной медицины», Санкт-Петербург, Россия &#13;
Санкт-Петербургский государственный университет, Санкт-Петербург, Россия</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Institute of Experimental Medicine, St. Petersburg, Russian Federation  &#13;
St. Petersburg State University, St. Petersburg, Russian Federation</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2016</year></pub-date><pub-date pub-type="epub"><day>08</day><month>12</month><year>2016</year></pub-date><volume>18</volume><issue>6</issue><fpage>545</fpage><lpage>554</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Леонтьева Г.Ф., Крамская Т.А., Грабовская К.Б., Филимонова В.Ю., Лайно Д., Виллена Д., Альварес С., Даниленко В.Н., Суворов А.Н., 2016</copyright-statement><copyright-year>2016</copyright-year><copyright-holder xml:lang="ru">Леонтьева Г.Ф., Крамская Т.А., Грабовская К.Б., Филимонова В.Ю., Лайно Д., Виллена Д., Альварес С., Даниленко В.Н., Суворов А.Н.</copyright-holder><copyright-holder xml:lang="en">Leontieva G.F., Kramskaya T.A., Grabovskaya K.B., Filimonova V.Y., Laiñ o J., Villena J., Alvares S., Danilenko V.N., Suvorov A.N.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.mimmun.ru/mimmun/article/view/1135">https://www.mimmun.ru/mimmun/article/view/1135</self-uri><abstract><p>Одной из наиболее актуальных задач медико-биологической науки является создание вакцинных препаратов против патогенных стрептококков – самых распространенных бактериальных возбудителей заболеваний человека, экономический ущерб от которых уступает лишь потерям от гриппозной инфекции. Входными воротами стрептококковой инфекции являются слизистые оболочки респираторного и мочеполового тракта.</p><p>Парентеральный способ введения вакцин не всегда позволяет добиваться одинаково эффективной стимуляции местного иммунитета на слизистых оболочках, а вакцины, вводимые через слизистые оболочки, способны эффективно стимулировать иммунную защиту в области введения, а также обеспечить развитие системного иммунного ответа.</p><p>Введение через слизистые оболочки вакцинных препаратов белковой природы требует использования специальных эффективных и безопасных адъювантов, поскольку рекомбинантные белки обычно проявляют недостаточную иммуногенность при таком способе введения. В работе в качестве вакцинных адъювантов при мукозальной иммунизации лабораторных животных пневмококковыми химерными рекомбинантными белками PSPF и PSP были апробированы два штамма пробиотиков – Lactobacillus rhamnosus CRL1505 и L32. Рекомбинантные химерные белки PSPF и PSP несут в своей структуре несколько иммуногенных эпитопов PspA, Spr1875, PsaA и предназначены для вакцинации против инфекции Streptococcus pneumoniae. Белки, отличие которых связано с присутствием в структуре PSPF участка молекулы флагеллина – FliC, по-разному стимулировали иммунный ответ при совместном введении с двумя штаммами пробиотиков. Установлено, что оба исследованных штамма L. rhamnosus были способны оказывать адъювантный эффект при интраназальном введении вакцинных белков, проявлявшийся в усилении секреторного и гуморального иммунного ответа на совместно введенный рекомбинантный химерный белок PSPF. Выраженной стимуляции продукции специфических IgA носовых смывов и IgG сыворотки крови на PSP под влиянием L. rhamnosus L32 не происходило. Адъювантный эффект от вводимых лактобациллярных препаратов существенно снижался после температурной инактивации бактерий, однако препарат клеточных стенок L. rhamnosus CRL1505 проявлял выраженную активность. Стимуляция иммунного ответа адъювантами приводила к усилению протективного эффекта вакцины в экспериментах на лабораторных животных, инфицированных S. pneumoniae.</p><p>Установлено, что некоторые штаммы лактобацилл, в частности Lactobacillus rhamnosus CRL1505 и L32, могут быть использованы в качестве адъювантов в составе мукозальных вакцин, однако эта способность зависит от свойств вакцинного препарата и формы введения пробиотиков.</p></abstract><trans-abstract xml:lang="en"><p>Vaccine protection against photogenic gram-positive bacteria including different species of streptococci is an important problem of contemporary molecular biology. Streptococcal infections are most common bacterial infections surpassing by the economic losses all the infections excluding influenza. The gates of streptococcal infection, oral cavity or vagina, are covered with immune and non-immune mucosal cells that are the first line of defenses. Subcutaneous immunization not always stimulate the local immunity on mucosal surfaces. On the other hand, mucosal vaccination can provide an appropriate local immune response together with systemic protection. However, mucosal immunization often requires usage of special and effective adjuvants especially in case of vaccines based on recombinant proteins.</p><p>For protection against Streptococcus pneumoniae infection, two chimeric recombinant proteins (PSPF and PSP) have been tested as vaccines. Recombinant proteins PSPF and PSP carry immunogenic epitopes from the respiratory pathogen including PspA, Spr1875 and PsaA. PSPF structure also carries a fraction of flagellin-FliC molecule in comparison with PSP, which does not have this fragment. This portion of PSPF was included as internal adjuvant intended for the stimulation of Toll-like receptor 5.</p><p>In this work, the adjuvant capacity of two probiotic strains, Lactobacillus rhamnosus CRL1505 and</p><p>L. rhamnosus L32 was evaluated. It was demonstrated that both lactic acid bacteria strains were able to provide adjuvant effects by enhancing the mucosal and systemic immune responses after their co-administration with the recombinant chimeric protein PSPF. The adjuvant effect of both Lactobacillus strains was significantly decreased after their thermal inactivation. However, the cell walls of bacteria showed a marked adjuvant activity. An improved protection against several S. pneumoniae serotypes after mucosal immunization of infant mice with PSPF vaccine with probiotic strains or their cell walls was also demonstrated here.</p><p>The recombinant chimeric protein PSPF administered with immunomodulatory probiotic strains or their bacterial components would be a promising vaccine for immunization of humans against S. pneumoniae, particularly in children.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>лактобациллы</kwd><kwd>пробиотики</kwd><kwd>рекомбинантные белки</kwd><kwd>мукозальные вакцины</kwd><kwd>адъюванты</kwd><kwd>пневмококковая инфекция</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Lactobacillus</kwd><kwd>probiotics</kwd><kwd>recombinant proteins</kwd><kwd>mucosal vaccines</kwd><kwd>adjuvants</kwd><kwd>pneumococcal infection</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Аверина О.В., Ермоленко Е.И., Ратушный А.Ю., Тарасова Е.А., Борщев Ю.Ю., Леонтьева Г.Ф., Крамская Т.А., Котылева М.П., Даниленко В.Н., Суворов А.Н. 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