Nucleic acid vaccines: tasks and tactics.

There are no adequate vaccines against some of the new or reemerged infectious scourges such as HIV and TB. They may require strong and enduring cell-mediated immunity to be elicited. This is quite a task, as the only known basis of protection by current commercial vaccines is antibody. As DNA or RNA vaccines may induce both cell-mediated and humoral immunity, great interest has been shown in them. However, doubt remains whether their efficacy will suffice for their clinical realization. We look at the various tactics to increase the potency of nucleic acid vaccines and divided them broadly under those affecting delivery and those affecting immune induction. For delivery, we have considered ways of improving uptake and the use of bacterial, replicon or viral vectors. For immune induction, we considered aspects of immunostimulatory CpG motifs, coinjection of cytokines or costimulators and alterations of the antigen, its cellular localization and its anatomical localization including the use of ligand-targeting to lymphoid tissue. We also thought that mucosal application of DNA deserved a separate section. In this review, we have taken the liberty to discuss these enhancement methods, whenever possible, in the context of the underlying mechanisms that might argue for or against these strategies.

Selective breeding for oral opioid acceptance or rejection in rats.

Lines of rats were selectively bred to diverge bidirectionally from a randomly bred control line in the propensity to self-administer an opioid orally. These lines seek or avoid the high-potency opioid etonitazene in a situation in which it is presented continuously as a choice with water. Over seven generations, preferences were measured and selection pressure imposed to develop the accepting and rejecting lines. These animals represent the only contemporary selective breeding program for opioid preference or self-administration, and hold the promise of being a useful resource in the drug-abuse field.