Protection Against Influenza Virus Infection In BALB/c Mice Immunized With A Single Dose Of Neuraminidase-expressing DNAs By Electroporation

Influenza is a highly contagious acute respiratory disease caused by infection of the host respiratory tract with influenza virus. The use of DNA vaccine seems to be a promising approach to the development of effective vaccines against influenza. This article consisting of three parts about our researches on influenza DNA vaccine.I. Present study is to evaluate the ability of plasmid DNA encoding neuraminidase (NA) or hemagglutinin (HA) from influenza virus A/PR/8/34 (PR8) (H1N1) to protect BALB/c mice against viral infection by a single administration. BALB/c mice were immunized with a single dose of 30 micrograms of NA or HA DNAs by electroporation and challenged with a lethal dose of influenza virus four weeks later. We found that immunization with 30 micrograms of NA DNA conferred complete protection against the lethal viral challenge, while HA failed to provide any protection against infection. In order to know whether NA could provide long-term protection against viral infection, mice were immunized with 30 microgram of NA or HA DNAs and challenged 28 weeks later. It was showed that the mice immunized with NA survived 100% compared 0% survival rate in the mice immunized with HA DNA. In another experiment, mice were immunized with 30, 10, 5 or 1 micrograms of NA DNA vaccine and challenged four weeks later. Interestingly, a single inoculation of 5 micrograms of NA DNA protected 80% of mice and higher doseof NA DNA protected 100% of mice, whereas 1 microgram of DNA failed to protect any mice. In addition, neonatal mice immunized with a single dose of 30 ug of NA DNA could be provided with significant protection against viral infection. These results indicate that a single inoculation of NA afford complete protection against a lethal influenza virus challenge. This simple and accelerated vaccine may contribute to control the epidemic spread of virus when influenza outbreaks.II. Maternal immunization is the major form of protection from many infectious diseases in early life. In this study, transmission of maternal vaccine-specific antibodies and protection of offspring against a lethal influenza virus challenge were studied. Adult female BALB/c mice were immunized with plasmid DNA encoding influenza virus hemagglutinin (HA), and HA-specific antibodies were measured in sera of offspring. Effective transmission of maternal antibodies was observed, and the antibodies lasted for several weeks but declined along with the growth of mice. The offspring, at age of 2 weeks, were protected against a lethal influenza virus challenge, in agreement with the high titer of maternal HA-specific antibodies. However, maternal HA-specific antibodies failed to protect 6-week-old offspring from the viral infection because of its low titer. These results suggest that HA DNA may be an effective vaccine for maternal immunization against influenza virus.III. This study is to evaluate an effective strategy to overcome the inhibitory effects of maternal antibody. For this purpose, mother mice were immunized...