Fd. Camargo et al., Germline incorporation of a replication-defective adenoviral vector in mice does not alter immune responses to adenoviral vectors, MOL THER, 2(5), 2000, pp. 496-504
The utility of adenoviral vectors is limited by immune responses to adenovi
ral antigens. We sought to develop immune-competent mice in which the immun
e response to adenoviral antigens was selectively absent. To do so, we gene
rated mice that were transgenic for a replicationdefective vector. Adenovir
al antigens might be seen as self-antigens by these mice, and the mice coul
d exhibit immunologic tolerance after postnatal exposure to adenoviral vect
ors. In addition, characterization of these mice could reveal potential con
sequences of germline transmission of an adenoviral vector, as might occur
in a gene therapy trial. Injection of a "null" (not containing a transgene)
E1, E3-deleted vector genome into mouse zygotes yielded five founders that
were capable of transmitting the vector genome. Among offspring of these m
ice, transgenic pups were significantly underrepresented: 108 of 255 pups (
42%) were transgenic (P < 0.02 versus expected frequency of 50%). Postnatal
transgenic mice, however, had no apparent abnormalities. Persistence of an
adenoviral vector after intravenous injection was equivalent in livers of
transgenic mice and their nontransgenic littermates. Transgenic and nontran
sgenic mice also had equivalent humoral and cellular immune responses to ad
enoviral vector injection. Mice that are transgenic for an E1, E3-deleted a
denoviral genome can be easily generated; however, they are not tolerant of
adenovirus. Moreover, germline transmission of an adenoviral vector genome
does not prevent generation of a robust immune response after exposure to
adenoviral antigens.