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English: Consequences of immunising individuals with or without pre-existing human adenoviral (HAd) vector immunity and its circumvention by using a nonhuman Ad or rare HAd vector. (a) Immunisation of an individual with high levels of pre-existing HAd vector immunity will lead to HAd vector-neutralisation in the presence of pre-existing HAd-neutralising antibodies, thereby lowering vector transduction of host cells, leading to reduced levels of transgene expression followed by lower levels of the transgene-specific immune responses. (b) In individuals with nonsignificant levels of HAd vector immunity, immunisation with a HAd vector will lead to robust innate and adaptive immune responses. The development of vector-specific cellular immune responses, significantly CD8 T cells, will eliminate the vector-transduced cells. (c) The use of a nonhuman Ad or rare HAd vector in individuals with or without pre-existing HAd vector immunity will have excellent transgene-specific immune responses.