CROSS-PROTECTION AMONG LETHAL H5N2 INFLUENZA-VIRUSES INDUCED BY DNA VACCINE TO THE HEMAGGLUTININ

Inoculation of mice with hemagglutinin (HA)-expressing DNA affords rel iable protection against lethal influenza virus infection, while in ch ickens the same strategy has yielded variable results, Here we show th at gene gun delivery of DNA encoding an H5 HA protein confers complete immune protection to chickens challenged,vith lethal H5 viruses, In t ests of the influence of promoter selection on vaccine efficacy, close correlations were obtained between immune responses and the dose of D NA administered, whether a cytomegalovirus (CMV) immediate-early promo ter or a chicken beta-actin promoter was used, Perhaps most important, the HA-DNA vaccine conferred 95% cross-protection against challenge w ith lethal antigenic variants that differed from the primary antigen b y 11 to 13% (HAL amino acid sequence homology), Overall, the high leve ls of protection seen with gene gun delivery of HA-DNA were as good as , if not better than, those achieved with a conventional whole-virus v accine, with fewer instances of morbidity and death. The absence of de tectable antibody titers after primary immunization, together with the rapid appearance of high titers immediately after challenge, implicat es efficient B-cell priming as the principal mechanism of DNA-mediated immune protection, Our results suggest that the efficacy of HA-DNA in fluenza virus vaccine in mice extends to chickens and probably to othe r avian species as well, Indeed, the H5 preparation we describe offers an attractive means to protect the domestic poultry industry in the U nited States from lethal H5N2 viruses, which continue to circulate in Mexico.