Strategies for inducing protection against avian influenza A virus subtypes with DNA vaccines

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 vacci nation with the highly conserved nucleoprotein gene appears to provide cros s protection against influenza A viruses in murine models. Whether such vac cines would protect human hosts against different influenza A viruses, incl uding strains with pandemic potential, is unclear. Our aim in this study is to evaluate the ability of a combination DNA vaccine consisting of two pla smids encoding the MA genes from two different subtypes and a DNA vaccine e ncoding the viral nucleoprotein gene From a H5 virus to induce protection a gainst highly lethal infection caused by H5 and H7 influenza viruses in chi ckens. Chickens given a single dose of plasmids expressing H5 and H7 hemagl utinins protected the birds from infection by either subtype. However, bird s 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, suggestin g inadequate immunity against viral infection. Fifty percent of the nucleop rotein DNA immunized birds survived infection by influenza A/Ty/Ir/1/83 (H5 N8) 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 d emonstrate that immunization with DNA encoding a type-specific gene may nor be effective against either homologous or heterologous strains of virus, p articularly if the challenge virus causes a highly Lethal infection. Howeve r. the combination of HA subtype vaccines are effective against lethal infe ction caused by viruses expressing any of the HA subtypes used in the combi nation preparation. (C) 2000 Elsevier Science Ltd. All rights reserved.