Prospects for control of emerging infectious diseases with plasmid DNA vaccines

Moss, Ronald B

Another novel mode of enhancing DNA vaccines has been a more invasive technique called electroporation. This method involves administration of brief electrical pulses of various voltages, after injection of a DNA vaccine, in order to enhance the uptake of DNA, presumably through the formation of transient pores in the muscle cell membrane. Many groups have shown encouraging results using electroporation in animals. One of the first groups to use this technique, Ulmer and colleagues, at Chiron Corporation, demonstrated that antibody and T-cell responses to the HIV protein Gag encoded in a DNA vaccine were enhanced by electroporation in rhesus macaques [23] . More recently, studies by Pavlakis and colleagues at the NIH have also noted that DNA potency measured by T-cell responses to the HIV protein Gag was augmented in nonhuman primates using electroporation [24] . Although encouraging in the strong magnitude of responses generated in animals, the wide clinical applicability of electroporation in humans in relation to tolerability remains to be determined. Some researchers have used plasmid DNA in what has been called a heterologous "prime-boost" vaccination approach. This method involves delivery of one or more plasmid DNA vaccine priming doses followed by a boost with a viral vector (such as adenovirus) which codes for the same antigens. In the prime-boost setting, DNA vaccination plays an important role in priming different types of T-cells (CD4+ and CD8+ T-cells) specific for various proteins. In studies, for example, by Nabel and colleagues at the NIH, DNA vaccination with plasmids encoding HIV antigens followed by a boost with an adenoviral vector carrying the same HIV gene sequences, resulted in stronger T-cell responses compared with adenoviral vector or DNA vaccine alone [25] . Similarly, Pantaleo and colleagues at the University of Lausanne have shown that a DNA vaccine for HIV followed by a boost with a poxvirus vector (NYVAC) resulted in stronger immune responses compared to immunization with pox vector alone [26] . In another prime-boost study, Jacobson and colleagues, at the University of California at San Francisco, immunized subjects with a DNA vaccine for CMV who were then boosted with a live-attenuated CMV virus (Towne strain). Faster and stronger virus-specific T-cell responses were observed in the group of subjects that received the DNA and Towne strain compared with a group of subjects that received the Towne strain alone [27] .