Several strategies have been developed to address the prevalence of pre-existing immunity to Ad5 in the general population. Increasing the vector dose or adopting a prime-boost regimen in order to overcome pre-existing immunity to the virus is a common approach [2] . There is mixed enthusiasm for this plan, however, due to the documented toxicity associated with high doses of adenovirus and the length of time required for primeboost regimens when only a prime could be sufficient [13, 14] . 'Seroswitching', using recombinant adenoviruses constructed from chimpanzees or rare human serotypes with limited exposure rates such as adenoviruses 35 and 11 can elicit potent immune responses that are minimally affected by pre-existing immunity [7, 8, [15] [16] [17] [18] [19] [20] [21] . Hexon-chimeric adenoviruses can also avoid neutralization [22, 23] . Both approaches offer promise in the context of addressing pre-existing immunity, but require further investigation in response to concerns regarding safety and feasibility of largescale production. Covalent attachment of polyethylene glycol or incorporation of the virus into polymer matricies can also effectively protect Ad5 from neutralization [24] [25] [26] [27] [28] [29] [30] [31] . Delivery of Ad5-based vaccines by mucosal routes can also circumvent the effect of pre-existing immunity and induce a significant immune response against an encoded antigen [32] .