A modified DNA vaccine to p53 induces protective immunity to challenge with a chemically induced sarcoma cell line

Author： Deng H. Kowalczyk D. O I. Blaszczyk-Thurin M. Quan Xiang Z. Giles-Davis W. Ertl H.C.J.

ISSN： 0008-8749

Source： Cellular Immunology, Vol.215, Iss.1, 2002-01, pp. : 20-31

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Abstract

Different vaccine constructs based on DNA vaccines and viral recombinant vaccines expressing mouse p53 were compared for induction of protective immune responses to challenge with a sarcoma cell line that expresses high levels of mutated p53 protein. Viral recombinant vaccines based on E1-deleted adenovirus or vaccinia virus recombinants expressing p53 with wild-type sequences in the mutational hotspot domain and a single mutation in the tetramerization domain (p53_mu338) failed to induce protection against progression of this tumor cell line. A DNA vaccine expressing a form of p53 carrying the same point mutations as the tumor cell line showed low efficacy that was comparable to that of a DNA vaccine expressingp53_mu338. Efficacy of the DNA vaccine was augmented upon expressingp53_mu338 as a fusion protein linked to a viral leader sequence. Other modifications such as fusion to the signal sequence of the lysosome-associated membrane protein (LAMP) or ubiquitin failed to improve the efficacy of the vaccine to p53. Protection mediated byCD4⁺ andCD8⁺ T cells was specific for p53.© 2002 Elsevier Science (USA)