IMMUNIZATION OF PIGS WITH A PARTICLE-MEDIATED DNA VACCINE TO INFLUENZA-A VIRUS PROTECTS AGAINST CHALLENGE WITH HOMOLOGOUS VIRUS

Particle-mediated delivery of a DNA expression vector encoding the hem agglutinin (HA) of an H1N1 influenza virus (A/Swine/Indiana/l726/88) t o porcine epidermis elicits a humoral immune response and accelerates the clearance of virus in pigs following a homotypic challenge. Mucosa l administration of the HA expression plasmid elicits an immune respon se that is qualitatively different than that elicited by the epidermal vaccination in terms of inhibition of the initial virus infection. In contrast, delivery of a plasmid encoding an influenza virus nucleopro tein from A/PR/8/34 (H1N1) to the epidermis elicits a strong humoral r esponse but no detectable protection in terms of nasal virus shed. The efficacy of the HA DNA vaccine was compared with that of a commercial ly available inactivated whole-virus vaccine as well as with the level of immunity afforded by previous infection. The HA DNA and inactivate d viral vaccines elicited similar protection in that initial infection was not prevented, but subsequent amplification of the infection is l imited, resulting in early clearance of the virus. Convalescent animal s which recovered from exposure to virulent swine influenza virus were completely resistant to infection when challenged. The porcine influe nza A virus system is a relevant preclinical model for humans in terms of both disease and gene transfer to the epidermis and thus provides a basis for advancing the development of DNA-based vaccines.