DNA Vaccines Based On Influenza Hemagglutinin Epitopes

Influenza continues to be a major threat to human society. The best option for reducing the impact of influenza is vaccination. As an attractive alternative to conventional attenuated or killed vaccines, DNA vaccine is a promising approach to be the influenza vaccine of the new generation because of its numerous advantages. Hemagglutinin, the most important surface antigen of influenza virus, is the best target for influenza DNA vaccines. And the protective antibodies are those induced by neutralizing epitopes on the surface of hemagglutinin protein. In this paper an exploratory study was performed on DNA vaccines based on influenza hemagglutinin epitopes.This article is made up of the following parts:1) a brief introduction to influenza, influenza vaccine and influenza hemagglutinin; 2) construction of DNA vaccines which contains one of the five epitopes of H1N1 influenza hemagglutinin and comparison of their protective efficacy in female BALB/c mice; 3) construction of a DNA vaccine which contains multi-epitopes of influenza hemagglutinin and evaluation of its cross-protective efficacy in female BALB/c mice;1) A brief introduction to influenza, influenza vaccine and influenza hemagglutinin:This part gives a guideline of the structure of influenza virion and mutation of influenza virus; it also gives a brief introduction to various influenza vaccines and characteristics of influenza hemagglutinin.2) Construction of DNA vaccines which contain one of the five epitopes of H1N1 influenza hemagglutinin and comparison of their protective efficacy in female BALB/c mice:In this paper we constructed a series of DNA vaccines based on the PR8 influenza HA1 which contains one of the five H1N1 influenza hemagglutinin epitopes. Female BALB/c mice were immunized by electroporation with 30μg of these DNA vaccines once, or immunized twice at an interval of three weeks. Three weeks after a single immunization or one week after boost, mice were challenged with a lethal dose of H1N1 influenza virus(20×LD50).The survival rates and body-weight losses were recorded, from which we could compare the immune efficacy of these DNA vaccines containing different epitope of H1N1 influenza hemagglutinin. The result showed that these DNA vaccines could provide mice a part protection against lethal influenza virus challenge after one immunization, and provide a nearly complete protection after boost.3) Construction of a DNA vaccine which contains multi-epitopes of influenza hemagglutinin and evaluation of its cross-protective efficacy in female BALB/c mice:In this part, a special DNA vaccine was constructed based on the H1N1 influenza HA1 which contains two epitopes of the PR8 influenza hemagglutinin. The DNA vaccine which encodes the intact PR8 influenza HA or H1N1 influenza HA were used as control. Female BALB/c mice were immunized by electroporation twice with 30μg of DNA vaccine at an interval of three weeks. And two weeks after last immunization, mice were challenged with a lethal dose of H1N1 influenza virus(20×LD50) or a lethal dose of PR8 influenza virus(20×LD50), respectively. The protective efficacy was evaluated by survival rates and body-weight losses. The result showed that the constructed DNA vaccine could provide mice a complete cross-protection against different influenza viruses infection with 100% survival rate, comparable to the DNA vaccines containing intact HA gene.