EXAMINATION OF PARAMETERS AFFECTING THE ELICITATION OF HUMORAL IMMUNE-RESPONSES BY PARTICLE BOMBARDMENT-MEDIATED GENETIC IMMUNIZATION

A human growth hormone expression construct was delivered intracellula rly into the abdominal skin of mice by particle bombardment-mediated g ene transfer. Using this technology, the in vivo delivery of antigen-e ncoding expression vectors affixed to gold microprojectiles results in de novo antigen production in target skin and development of specific antibody responses. In this study, we examined the contribution of va rious delivery parameters to the resultant protein expression and rela ted antibody responses. The highest levels of both protein expression and antibody production were correlated with particle delivery to the epidermis while deliveries extending into the dermis resulted in decre ased protein and antibody production. Optimal immune responses were al so shown to be dependent upon the delivery of a sufficient number of D NA-coated gold particles, indicating that a dose-response relationship exists between the number of particles delivered and the resultant pr otein expression and antibody production. Further, maximal protein exp ression and associated antibody titers were elicited with surprisingly small amounts of DNA. The practicality of targeting skin and the use of three to four orders of magnitude less DNA than is typically requir ed in direct DNA inoculation studies demonstrates the potential utilit y of this emerging technology for the rapid production of antibodies i n laboratory animals, and in the development of a new class of human c linical vaccines based upon direct, intracellular DNA delivery.