**7.2 Future applications**

While the current VZV vaccine is sufficient to prevent chickenpox, many issues still surround this live attenuated vaccine. Firstly, bulk vaccine production using the vOka strain is difficult and costly due to vOka virus's relatively low yield (Schmid & Jumaan, 2010; Gomi et al, 2002). The vaccine is also not entirely effective at eliminating chickenpox outbreaks. Despite seroconversion after vaccination, varicella infections still occur in some children and adults exposed to wild-type VZV (Schmid & Jumaan, 2010; Bernstein et al., 1993, White et al., 1991). Most significantly however, the currently marketed vaccine strain, v-Oka, while highly attenuated in the skin, still retains its neurovirulence (Hambleton et al., 2008). This means that the virus will continue to establish latency in the sensory nerve ganglia of the immunized host and can potentially reactivate later to trigger herpes zoster and post-herpetic neuralgia. Furthermore, while drug treatments available to date can alleviate some symptoms of VZV-elicited diseases and shorten the disease duration, they cannot clear the virus or prevent establishment of latency (Miwa et al., 2005; Hatchette et al., 2008). For these reasons, developing a new neuro-attenuated vaccine is imperative to prevent future herpes zoster in both elderly people and vaccinated children.

The use of viral BACs has great potential for novel vaccine development and future treatment of viral diseases. Our studies using the VZVLuc BAC uncovered the first, and plausibly the only, VZV neurotropic factor, ORF7. Because the ORF7D strain is incapable of infecting both human skin and nervous tissue *in vivo*, the deletion virus may serve as an ideal vaccine candidate for the next generation of chickenpox and shingles vaccines. Aside from using the ORF7 deletion virus to produce a safer neuro-attenuated vaccine for the prevention of herpes zoster, the same deletion virus may also be utilized as a potential viral vector for the production of vaccines against other pathogens as well.

Additional research into this BAC-based candidate is needed to lead us closer to designing neuro-attenuated vaccines that do not establish latency in sensory neurons, and thereby eliminate the risk of recurrent herpes zoster and its complications. In time, the development of safe and effective neuro-attenuated vaccines will decrease the likelihood of herpes zoster in the contemporary susceptible population, reduce herpes zoster-associated costs, and potentially eradicate VZV and VZV-related diseases (Lydick et al., 1995; Drolet et al., 2010). Essentially, these new vaccines will change the future of VZV altogether.
