DNA vaccines for avian influenza-a model for future poultry vaccines?

We investigated the utility of DNA vaccines for protecting the avian systems from lethal influenza virus infections. Gene-gun delivery of DNA encoding an H5 HA protein confered complete immune protection to chickens challenged with lethal H5 viruses. A cytomegalovirus immediate early promoter and a chicken beta-action promoter were similar in effectiveness, immune responses were closely correlated with the dose of DNA administered. Importantly, the HA-DNA vaccine conferred 95% cross-protection against challenge with lethal antigenic variants that differed from the primary antigen by 11%-13% (HA1 amino acid sequence homology). As measured by morbidity and death rates gene-gun delivery of HA-DNA provided as good as or better than that achieved with a conventional inactivated whole-virus vaccine. Highly efficient immunization was achieved by gene gun delivery of DNA to the epidermis, requiring 20 times less DNA than used in saline injections. The absence of detectable antibody titers after primary immunization, together with the rapid appearance of high titers immediately after challenge, implicated efficient B-cell priming as the principal mechanism of DNA-mediated immune protection. Bursectomy prevented the protective effect of the vaccine, suggesting that the B-cell memory response plays an important role. Preliminary data from B-cell responsiveness to virus challenge suggests that the bone marrow and spleen participate in the development of immune response. We have shown that a single gene gun inoculation of chickens with DNA encoding the influenza virus hemagglutinin results in life-long protection against otherwise lethal infection. This finding is particularly applicable to layer and breeder chickens, in which longer-lived immunity is needed. DNA immunization has potential to control the majority of viral, bacterial and parasitic infections of poultry.