The negative effect of the pre-existing or Ad5-induced immunity against the vaccine, mostly when the therapy requires multiple dosages, may be overcome by heterologous prime-boost regimen. The utility of the rare human serotypes (e.g., serotype 35) [149, 150] or recombinant adenoviruses of nonhuman origin has been recently tested [151] . In particular, subsequent priming immunizations with plasmid DNA vaccine followed by a booster vaccination with AdV seem to be a very promising strategy. DNA primeadenovirus boost regimen proved to induce more robust and potent immune response in comparison to plasmid DNA alone and provided protection against the pathogen challenge in several animal models of infectious diseases [149, [152] [153] [154] . Furthermore, a clinical trial of multiclade HIV-1 DNA plasmid-Ad5 boost vaccine, HIVuninfected individuals demonstrated high immunogenicity even in the presence of high anti-Ad5 antibody titer. In addition, the vaccine proved to be well tolerated in the participants of the study [155] .