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 following successive immunizations. The codelivery of vectors encoding IL-2, IL-7, or IL-12 blocked this effect by markedly enhancing gp120-specific interferon gamma production, and suppressing IL-4 and IgG1 responses. 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 1000-fold, while IL-4, IgG1, and IgG2a responses were elevated as well. Interestingly, cytokine gene codelivery, in the context of the longer resting period, provided no additional stimulation of Th1-like responses such as IFN-gamma and IgG2a production, although there was still some suppression of IL-4 production. These data demonstrate that the quality and magnitude of responses elicited following epidermal administration of DNA vaccines can be manipulated by multiple means.