DNA vaccine encoding hemagglutinin provides protective immunity against H5N1 influenza virus infection in mice

Abstract

In Hong Kong in 1997, a highly lethal H5N1 avian influenza virus was apparently transmitted directly from chickens to humans with no intermediate mammalian host and caused 18 confirmed infections and six deaths. Strategies must be developed to deal with this virus if it should reappear, and prospective vaccines must be developed to anticipate a future pandemic. We have determined that unadapted H5N1 viruses are pathogenic in mice, which provides a well-defined mammalian system for immunological studies of lethal avian influenza virus infection. We report that a DNA vaccine encoding hemagglutinin from the index human influenza isolate A/HK/156/97 provides immunity against H5N1 infection of mice. This immunity was induced against both the homologous A/HK/156/97 (H5N1) virus, which has no glycosylation site at residue 154, and chicken isolate A/Ck/HK/258/97 (H5N1), which does have a glycosylation site at residue 154. The mouse model system should allow rapid evaluation of the vaccine's protective efficacy in a mammalian host. In our previous study using an avian model, DNA encoding hemagglutinin conferred protection against challenge with antigenic variants that differed from the primary antigen by 11 to 13% in the HA1 region. However, in our current study we found that a DNA vaccine encoding the hemagglutinin from A/Ty/Ir/1/83 (H5N8), which differs from A/HK/156/97 (H5N1) by 12% in HA1, prevented death but not H5N1 infection in mice. Therefore, a DNA vaccine made with a heterologous H5 strain did not prevent infection by H5N1 avian influenza viruses in mice but was useful in preventing death.

FIG. 1

HI antibody titers of mice immunized with pHKHA and challenged with either HK97 or CkHK97. Serum samples were collected at 10 days postbooster (prechallenge) and at 10 days postchallenge. HI determinations were done with either HK97 or CkHK97 virus antigens. Each bar represents a titer from an individual mouse.

FIG. 2

HI antibody titers of mice immunized with pTyIrHA and challenged with HK97. Serum samples were collected at 10 days postbooster (prechallenge) and at 10 days postchallenge. There were no detectable antibodies in the serum samples collected from mice after booster. HI determinations were done with either HK97 or CkHK97 virus antigens. Each bar represents a titer from an individual mouse.