IDENTIFICATION OF FUNCTIONAL DOMAINS OF ADENOVIRUS TUMOR-SPECIFIC TRANSPLANTATION ANTIGEN IN TYPE-5 AND TYPE-12 BY VIABLE VIRUSES CARRYING CHIMERIC E1A GENES

The adenovirus (Ad) EIA gene induces in immunized animals a strong tum or transplantation (TSTA) immunity against Ad tumors. Such immunity wi th group-A and group-C viruses is highly group-specific and no cross-p rotection is detected between serotypes 5 and 12. This fact was used t o map the domains of the Ad5 and Ad12 EIA gene products, respectively, which control the TSTA. We constructed a library of 8 recombinant vir uses (H5sub1101 through H5sub1108) which carry chimeric Ad5/Ad12 EIA g enes in the background of Ad5. The chimeric genes are functional and t hese viruses are viable. Some of these constructs induce strong and hi ghly specific tumor syngraft immunity in immunized rats. The viruses c arrying the 5' terminus of the first EIA exon derived from Ad12 (virus es H5sub1101, H5sub1102 and H5sub1103) induce strong protection agains t Ad12 tumors irrespective of the rest of their EIA sequence. The viru ses which carry the second exon of the Ad5 EIA gene (viruses H5sub1101 , H5sub1102 and H5sub1106) protect against group-C tumors, regardless of the origin of the rest of their EIA gene. The 2 viruses that carry the 5' EIA terminus of the first exon Ad12 and the second exon of Ad5 (H5sub1101 and H5sub1102) are thus effective in inducing immunity agai nst Ad12 tumors as well as against Ad2 tumors. The viruses which carry the 5' terminus of the first exon derived from Ad5 and the second exo n of Ad12 (H5sub1107 and H5sub1108) fail to induce immunity against ei ther tumor. Expression of only the truncated 5' terminus of the Ad12 E IA gene (viruses H5sub1104 and H5sub1105) is sufficient for induction of Ad12 TSTA. Our results provide direct and unequivocal in vivo evide nce that TSTA activities of adenovirus groups A and C are controlled b y different domains of their respective EIA genes. The Ad12 TSTA is a function of the 5' terminus of the first EIA exon, while the Ad5 TSTA is coded for by the 3' exon of its EIA gene. (C) 1994 Wiley-Liss, Inc.