biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Productsbiopreparat-36Research ArticleОБЗОРЫREVIEWSМенингококковая инфекция. Конъюгированные полисахаридные менингококковые вакцины и вакцины нового поколения. Сообщение 3Meningococcal disease. Meningococcal conjugate polysaccharide vaccines and new generation vaccines. Report 3АбрамцеваМ. В.AbramtsevaM. V.

Эксперт 1-й категории лаборатории бактериальных вакцин Испытательного центра экспертизы качества МИБП

1st category expert of Laboratory of bacterial vaccines of Test Center of Quality Expertise of medical immunobiological preparations

Abramtceva@expmed.ruТарасовА. П.TarasovA. P.

Эксперт 1-й категории лаборатории бактериальных вакцин Испытательного центра экспертизы качества МИБП, канд. биол. наук

1st category expert of Laboratory of bacterial vaccines of Test Center of Quality Expertise of medical immunobiological preparations. Candidate of Biological Sciences

noemail@neicon.ruНемировскаяТ. И.NemirovskayaT. I.

Начальник лаборатории бактериальных вакцин Испытательного центра экспертизы качества МИБП, канд. мед. наук

Head of Laboratory of bacterial vaccines of Test Center of Quality Expertise of medical immunobiological preparations. Candidate of Medical Sciences

noemail@neicon.ruНаучный центр экспертизы средств медицинского примененияРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation201620022018161313Copyright © Абрамцева М.В., Тарасов А.П., Немировская Т.И., 20182018Абрамцева М.В., Тарасов А.П., Немировская Т.И.Abramtseva M.V., Tarasov A.P., Nemirovskaya T.I.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/36

Несмотря на прогресс, достигнутый в области борьбы с инфекционными заболеваниями бактериальной природы, заболеваемость генерализованными формами менингококковой инфекции (ГФМИ) остается весьма актуальной проблемой для здравоохранения не только в странах с исторически сложившейся высокой заболеваемостью, но и в странах, считающихся вполне «благополучными» в отношении этой инфекции. В 60-х годах прошлого века было освоено производство высокополимерных форм полисахаридов менингококка. Эти высокомолекулярные полисахариды были использованы для разработки вакцин. С их помощью удалось весьма существенно снизить заболеваемость ГФМИ в ряде стран, в том числе в странах так называемого африканского «менингитного пояса». К сожалению, полисахаридные вакцины не лишены известных недостатков, что побудило исследователей к разработке более перспективных конъюгированных вакцин. Разработанные к настоящему времени вакцины нового поколения созданы на основе конъюгатов полисахаридов различных серогрупп с белками-носителями, такими как столбнячный анатоксин, модифицированный дифтерийный токсин (CRM197) или белки наружной мембраны. Были разработаны и апробированы моно- и поливалентные конъюгированные вакцины. Конъюгированные вакцины обладают рядом преимуществ по сравнению с полисахаридными. Они стимулируют образование иммунологической памяти, поэтому способны обеспечивать стойкую защиту от менингококковой инфекции у детей ранней возрастной группы. В частности, весьма эффективной оказалась моновалентная конъюгированная вакцина против менингококка серогруппы С. Данная вакцина с успехом была применена в Великобританнии. Известны также тетравалентные конъюгированные вакцины Menactra и Menveo. В этих препаратах использовались конъюгаты менингококковых полисахаридов серотипов A, C, W135 и Y. Эти полисахариды стимулировали выработку бактерицидных антител у 90% иммунизированных лиц. Известного успеха также удалось достичь в области создания генно-инженерных вакцин и вакцин, сконструированных на основании везикул наружной мембраны менингококка (OMV-вакцин). OMV-вакцины продемонстрировали свою эффективность в борьбе с эпидемиями менингита, вызванными менингококком серогруппы В. Полисахаридные вакцины против менингококка серогруппы В в разных конструктивных вариантах оказывались неэффективными ввиду их низкой иммуногенности. Созданию полноценной вакцины, защищающей от ГФМИ, вызванных менингококком серогруппы В, препятствует большое разнообразие антигенных вариантов данного микроба. До настоящего времени удалось создать только штаммо-специфические вакцины, пригодные для борьбы со вспышками ГФМИ, вызванными конкретным штаммом менингококка серогруппы В. Обсуждаются перспективы повышения эффективности вакцин против менингококка серогруппы В.

Despite the progress in fighting against infectious diseases of bacterial origin, the incidence of generalized forms of meningococcal infection (GFMI) remains a topical public health problem not only in countries with historical high incidence, but also in countries considered to be relatively «secured» in regard to the mentioned infection. In the 60s of the last century the production of high-polymer forms of meningococcal polysaccharides was started. These high molecular weight polysaccharides were used for the development of vaccines. They helped to significantly reduce the incidence of GFMI in certain countries, including the countries of the so-called African «meningitis belt». Unfortunately, polysaccharide vaccines have well-known deficiencies, prompting the researchers to develop advanced conjugate vaccines. Current new generation of vaccines are based on conjugates of polysaccharides of different serogroups with carrier proteins such as tetanus toxoid, a modified diphtheria toxin (CRM197) or outer membrane proteins. Mono- and multivalent conjugate vaccines were developed and tested. Conjugate vaccines have several advantages compared to the polysaccharide vaccines. They stimulate the formation of immunological memory, and therefore are able to provide consistent protection against meningococcal disease in children of an early age group. In particular, monovalent conjugate vaccine against serogroup C meningococcal disease were proven to be very effective. This vaccine was successfully used in the UK. There are also tetravalent conjugate vaccines Menactra and Menveo. These preparations consist of serotype A, C, W135 and Y meningococcal polysaccharide conjugates. These polysaccharides stimulated the production of bactericidal antibodies in 90% of immunized individuals. Certain success was also achieved in developing genetically engineered vaccines and the vaccines based in meningococcal outer membrane vesicles (OMV-vaccines). OMV-vaccines showed to be effective in the fight against epidemics of meningitis caused by serogroup B meningococcus. Polysaccharide vaccines against serogroup B meningococcus in different designs proved to be ineffective because of their low immunogenicity. There are certain difficulties in developing an ultimate vaccine that protects against GFMI, due to the fact that there is a variety of antigenic types of serogroup B meningococcus. So far the scientists only have managed to develop a strain-specific vaccine suitable for fighting GFMI outbreaks, caused by the specific strain of serogroup B meningococcus. The opportunities to enhance the efficacy of vaccines against serogroup B meningococcus are still being discussed.

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