| 主权项 |
1. A method of priming an immune response to a target expressed from a boosting adenovirus without priming an anti-adenovirus immune response to the subsequently administered boosting adenovirus, comprising:
(a) administering a priming dose of an E1-deleted, E4-deleted adenovirus having a capsid of a first serotype, the priming adenovirus comprising an adenovirus genome comprising sequences encoding the adenovirus E3 gene operably linked to expression control sequences which direct expression of the E3 gene product and a functional deletion in at least adenovirus early genes E1 and E4, said genome further comprising a heterologous expression cassette comprising a nucleic acid sequence encoding a product for inducing an immune response to a target under the control of regulatory control sequences which direct expression of the product, which expression cassette is located in the site of the E1 deletion or the E4-deletion, wherein the priming adenovirus confers reduced anti-adenovirus immune response to the subsequently administered boosting adenovirus; and (b) administering the boosting dose of an adenovirus which is an E1-deleted adenovirus having a capsid of a second serotype that differs from the first serotype, the boosting adenovirus further comprising an adenovirus genome comprising heterologous expression cassette comprising nucleic acid sequence encoding the product for inducing an immune response to the target or a cross-reactive target under the control of regulatory control sequences which direct expression of the product in the site of the E1 deletion, the genome further comprising a functional deletion in at least the E1 gene, wherein the boosting E1-deleted adenovirus is administered after said priming adenovirus, wherein the immune responses to the product of the boosting adenovirus are greater. |
