The cross-species transfer of a H5N1 influenza virus from birds to humans, and the systemic spread of this virus in mice, has accelerated the efforts to devise protective strategies against lethal influenza viruses.
DNA vaccination with the highly conserved
nucleoprotein gene appears to provide cross protection against influenza A viruses in murine models. Whether such
vaccines would protect human hosts against different influenza A viruses, including strains with pandemic potential, is unclear. Our aim in this study is to evaluate the ability of a combination
DNA vaccine consisting of two plasmids encoding the HA genes from two different subtypes and
a DNA vaccine encoding the viral
nucleoprotein gene from a H5 virus to induce protection against highly lethal
infection caused by H5 and H7 influenza viruses in chickens. Chickens given a single dose of plasmids expressing H5 and H7
hemagglutinins protected the birds from
infection by either subtype. However, birds immunized with
nucleoprotein DNA and challenged with either A/Ck/Vic/1/85(H7N7) or A/Ty/Ir/1/83 (H5N8) showed definite signs of
infection, suggesting inadequate immunity against
viral infection. Fifty percent of the
nucleoprotein DNA immunized birds survived
infection by
influenza A/Ty/Ir/1/83 (H5N8) virus (virus of same subtype) while 42% survived
infection by
influenza A/Ck/Vic/1/85/(H7N7) virus (virus of a different subtype). These studies demonstrate that immunization with
DNA encoding a type-specific gene may not be effective against either homologous or heterologous strains of virus, particularly if the challenge virus causes a highly lethal
infection. However, the combination of HA subtype
vaccines are effective against lethal
infection caused by viruses expressing any of the HA subtypes used in the combination preparation.