ТАРГЕТНАЯ ВАКЦИНАЦИЯ ПРОТИВ СТРЕПТОКОККА ГРУППЫ A: РЕКОМБИНАНТНАЯ ВАКЦИНА С ФРАГМЕНТАМИ SCPA И SPEA

Резюме

Цель: разработка вакцины против стрептококков группы А (S. pyogenes, СГА) – возбудителя широкого спектра инфекций различной степени тяжести.

Методы: Для клонирования генов рекомбинантных белков использовали экспрессионные вектора pET27 и pQE30. Для иммунизации использовали аффинно-очищенные полипептиды. Самок мышей иммунизировали дважды подкожно полипептидами в дозе 20 мкг/мышь с адъювантом Alum (2:1) с интервалом в 3 недели. Образцы иммунных сывороток исследовали методом ИФА. Для оценки специфической защитной эффективности иммунного ответа через 3 недели после последней инъекции мышей внутрибрюшинно заражали СГА M1 серотипа в дозе 5х10^7 КОЕ/мышь. Защитную эффективность вакцинации оценивали путем сравнения скорости бактериального клиренса у вакцинированных и контрольных животных, о чем судили по бактериальной нагрузке в селезенке через 3 и 15 часов после заражения.

Результаты: Конструкция вакцины представляет собой гибридную молекулу, состоящую из фрагментов, полученных из двух ключевых белков СГА: пептидазы C5a (ScpA) и экзотоксина SpeA. Используя биоинформатический анализ, мы идентифицировали и выбрали для включения в состав рекомбинантного белка Т- и В-клеточные эпитопы в консервативных регионах, общих для разных серотипов СГА.

Посредством стратегии интеграции этих фрагментов предполагается усилить защиту от штаммов СГА, несущих экзотоксин, особенно тех, которые связаны с инвазивными инфекциями.

Оценка иммуногенности на моделях мышей продемонстрировала сильный гуморальный иммунный ответ после парентеральной вакцинации, направленный на оба компонента гибридной молекулы. Последующая оценка защитной эффективности против внутрибрюшинного введения СГА выявила ускорение бактериального клиренса у вакцинированных животных, при этом фрагмент SpeA проявлял значительный защитный эффект.

Заключение: Представленные результаты демонстрируют потенциал полученной рекомбинантной химерной вакцины как многообещающего кандидата для разработки вакцины против стрептококков группы А, удовлетворяющей острую потребность в эффективных профилактических стратегиях против патологий, вызванных СГА.

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