Основные этапы и перспективы создания вакцин против вирусного гепатита С

02.12.2012

Л.И. Николаева1 (L.i.nikolaeva@mail.ru), Г.В. Сапронов2, Н.М. Беляева2

1ФГБУ «НИИ вирусологии им. Д.И. Ивановского» Минздрава России, Москва 2ГБОУ ДПО «Российская медицинская академия последипломного образования», Москва

Резюме

Цель обзора - проанализировать основные этапы разработки вакцин против гепатита С, отметить основные проблемы и перспективы создания. В обзоре представлены данные по иммунотерапевтическим и профилактическим вакцинам, находящимся на разных этапах испытаний.

Ключевые слова: вирусный гепатит С, Т- и В-клеточный ответ, вакцины-кандидаты

The Main Stages and Perspectives of Vaccine Development аgainst Hepatitis C

L.I. Nikolaeva1 (L.i.nikolaeva@mail.ru), G.V. Sapronov2, N.M. Belyaeva2

federal Budgetary State Institution «D.I. Ivanovsky Institute of Virology»of Ministry of Healthcare of the Russian Federation, Moscow 2State Budgetary Educational Institution of Additional Professional Education «Russian Medical Academy of Post-Degree Education», Moscow Abstract

The aim of this review was to analyze the main stages of vaccine development against hepatitis C, to note the principal problems, which hinder this work, and display perspectives of its creation. After identification of HCV investigation of vaccine design have begun. The fact of very rare spontaneous recover after an acute hepatitis C (20 - 30%) testified that HCV has possibilities to escape immune control and that development of antiviral vaccine will depend in many respects on studying of the virus molecular biology and human immune response.

The first stage in vaccine creation has had on the middle of 1990th years of the last century when have been received recombinant viral envelope proteins in Chiron Corporation. An experimental immunization chimpanzees by these proteins and the subsequent infection with the viral isolate showed that the envelope proteins can induce antibody in high titers. But protective ability of anti-E1 and anti-E2 antibodies was low. Only several of animals were protected.

The second stage in the vaccines development began in second half of 1990th years when important role of T-helper (CD4+) and T-killer (CD8+) lymphocytes in infection restriction will be revealed. New design of vaccines on CTL (cytotoxic T lymphocytes) epitopes have begun. It was planned to use these vaccine in therapeutic purposes. In the beginning of 2000th years Chiron Corporation has prepared the first model of such vaccine for clinical trial, which have finished unsuccessfully. Several patients showed rising of liver fibrosis after the vaccination. It has been caused by high activation of CTL.

In the beginning of 2000th years the important information about role of virus-neutralizing antibodies (VNA), T-helper lymphocytes, and surface hepatocytes proteins as receptors and co-receptors has been received. These data has allowed to create new design of HCV vaccines. B- and T-cell epitopes from envelope, core, NS3, NS5a proteins were included in such vaccines, which induce VNA and T-cell response. Recently an optimistic publication about immunization of 8 healthy volunteers with recombinant envelope glycoproteins was done [Stamataki Z. et al., 2011]. In this article VNA with reactivity to HCV subtypes 1а, 1b, and 2a, was detected. There are an experimental data about main variants of therapeutic and prophylactic vaccines in two tables of this review. Some of experimental vaccines are in stage I/II of trials. According to the view of the experts, therapeutic vaccines will be done firstly.

Key words: viral hepatitis C, T- and B-cell response, candidate vaccine