Genetic immunization with lung-targeting macroaggregated polyethyleneimine-albumin conjugates elicits combined systemic and mucosal immune responses

Genetic immunization is a novel form of vaccination in which transgenes are delivered into the host to produce the foreign protein within host cells. Although systemic immune responses have been relatively easy to induce by g enetic immunization, the induction of regional and mucosal immunity has oft en been more challenging. To address the problem of eliciting mucosal immun ity in the lung, we utilized macroaggregated albumin to target plasmid DNA to the lung, Macroaggregated albumin is trapped in the lung after i.v. inje ction, and it is routinely used in radiolabeled form as an imaging modality to evaluate pulmonary blood how, To couple DNA to this targeting agent, po lyethyleneimine (a polycation that binds DNA and enhances transfection) was conjugated to serum albumin, and the conjugate was aggregated by heating t o produce particles of 25-100 mu m The resulting particles bound plasmid DN A avidly, and when injected i.v. in mice, the particles distributed in the peripheral lung tissue in the alveolar interstitium, Particle-bound lucifer ase plasmid transfected a variety of cell lines in vitro, and after i.v. in jection, gene expression was detected exclusively in the lung. Using human growth hormone as the encoded foreign Ag for immunization, i.v. injection o f the particle-bound plasmid elicited both pulmonary mucosal and systemic i mmune responses, whereas naked DNA injected either i.v. or i.m. elicited on ly systemic responses. Thus, particle-bound plasmid DNA may have utility fo r genetic immunization by intravascular delivery to the lung and potentiall y to other organs and tissues.