MANIPULATION OF HIV-1 GP120-SPECIFIC IMMUNE-RESPONSES ELICITED VIA GENE GUN-BASED DNA IMMUNIZATION

Gene gun-based DNA immunization using vectors encoding HIV-1 gp120 or influenza virus nucleoprotein result in Th2-like immune responses foll owing successive immunizations. The codelivery of vectors encoding IL- 2, IL-7, or IL-12 blocked this effect by markedly enhancing gp120-spec ific interferon gamma production, and suppressing IL-4 and IgG1 respon ses. An unbiased augmentation of all immune responses was observed by increasing the resting period between immunizations. In this case, IFN -gamma production following in vitro stimulation increased by over 100 0-fold, while IL-4, IgG1, and IgG2a responses were elevated as well. I nterestingly, cytokine gene codelivery, in the context of the longer r esting period, provided no additional stimulation of Th1-like response s such as IFN-gamma and IgG2a production, although there was still som e suppression of IL-4 production. These data demonstrate that the qual ity and magnitude of responses elicited following epidermal administra tion of DNA vaccines can be manipulated by multiple means. (C) 1997 El sevier Science Ltd.