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

In Hong Kong in 1997, a highly lethal H5N1 avian influenza virus was appare ntly transmitted directly from chickens to humans with no intermediate mamm alian host and caused 18 confirmed infections and six deaths. Strategies mu st be developed to deal with this virus if it should reappear, and prospect ive vaccines must be developed to anticipate a future pandemic. We have det ermined that unadapted H5N1 viruses are pathogenic in mice, which provides a well-defined mammalian system for immunological studies of lethal avian i nfluenza virus infection. We report that a DNA vaccine encoding hemagglutin in from the index human influenza isolate A/HK/156/97 provides immunity aga inst H5N1 infection of mice. This immunity was induced against both the hom ologous A/HK/156/97 (H5N1) virus, which has no glycosylation site at residu e 154, and chicken isolate A/Ck/HK/258/97 (H5N1), which does have a glycosy lation site at residue 154. The mouse model system should allow rapid evalu ation of the vaccine's protective efficacy in a mammalian host. In our prev ious study using an avian model, DNA encoding hemagglutinin conferred prote ction against challenge with antigenic variants that differed from the prim ary antigen by 11 to 13% in the HA1 region. However, in our current study w e found that a DNA vaccine encoding the hemagglutinin from A/Ty/Ir/1/83 (H5 N8), which differs from A/HK/156/97 (H5N1) by 12% in HA1, prevented death b ut not H5N1 infection in mice. Therefore, a DNA vaccine made with a heterol ogous H5 strain did not prevent infection by H5N1 avian influenza viruses i n mice but was useful in preventing death.