Совершенствование способа получения моноклональных антител к структурному белку р30 вируса АЧС с использованием рекомбинантных конструкций тема диссертации и автореферата по ВАК РФ 06.02.02, кандидат ветеринарных наук Першин, Андрей Сергеевич

• Першин, Андрей Сергеевич
• кандидат ветеринарных наук
• 2013

Оглавление диссертации кандидат ветеринарных наук Першин, Андрей Сергеевич

Список сокращений.

1 Введение.

1.1 Актуальность работы.

1.2 Степень разработанности проблемы.

1.3 Цель и задачи исследования.

1.4 Научная новизна результатов исследования.

1.5 Теоретическая и практическая значимость работы.

1.6 Степень достоверности и апробация работы.

1.7. Публикации.

1.8 Структура диссертации.

1.9 Основные положения диссертации, выносимые на защиту.

1.10 Личный вклад автора в выполнение работы.

2 Обзор литературы.

2.1 Африканская чума свиней.

2.1.1 Характеристика, распространение и экономический ущерб.

2.1.2 Диагностика.

2.2 Моноклональные антитела.

2.2.1 Открытие и применение гибридом продуцентов моноклональных антител.

2.2.2 Развитие гибридомной биотехнологии.

2.2.2.1 Иммунизация для получения моноклональных антител.

2.2.2.2 Культивирование гибридом.

2.2.2.3 Биспецифические МкАт.

2.2.2.4 Рекомбинантные МкАт.

2.2.2.5 Искусственные антитела.

Введение диссертации (часть автореферата) на тему «Совершенствование способа получения моноклональных антител к структурному белку р30 вируса АЧС с использованием рекомбинантных конструкций»

1.1 Актуальность работы

Африканская чума свиней (АЧС) - вирусная болезнь, характеризующаяся контагиозностью и летальностью, получила в настоящее время широкое распространение на европейской территории Российской Федерации.

Одним из основных белков вируса АЧС является структурный белок урЗО входящий в состав внутренней мембраны вириона. урЗО имеет важное диагностическое значение, поскольку синтезируется на ранних и поздних стадиях инфицирования и является высококонсервативным белком, присущим большинству известных изолятов вируса АЧС. Данные факты объясняют перспективность получения и изучения моноклональных антител, специфичных к указанному белку.

В доступной литературе имеется ограниченное количество работ посвященных использованию ДНК-иммунизации для получения МкАт.

Обычно при получении МкАт в качестве иммуногена используют очищенные и концентрированные вирусные антигены. Однако даже при высокой степени их очистки не удаётся избавиться от примеси балластных контаминирующих антигенов, часто имеющих высокую иммуногенность [17].

Использование рекомбинантных конструкций для иммунизации мышей с целью получения МкАт заданной специфичности позволяет исключить недостатки использования вирусных антигенов, так как устраняет наличие контаминирующих антигенов, тем самым достигается стандартизация и чистота иммуногена.

ДНК-иммунизация как метод доставки генетического материала имеет ряд преимуществ перед иммунизацией белками. Наиболее важным является запуск обоих ветвей иммунного ответа, что обеспечивает высокое качество В-лимфоцитов для слияния, а так же увеличивает долю антител, специфичных к конформационным эпитопам заданного белка.

S. Mazumder et al. (2011) при изучении индукции и длительности иммунного ответа у мышей линии BALB/c при различных комбинациях ДНК/белок показали преимущество иммунизации с праймированием ДНК-плазмидой и последующим введением белка в растворимой форме [141].

Использование рекомбинантных антигенов и моноклональных антител, полученных на их основе, также позволяет совершенствовать иммунодиагностику, причем, эти подходы фактически позволяют исключить использование высокопатогенных инфекционных агентов при производстве диагностических тест-систем.

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