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Priming polyvalent immunity by DNA vaccines expressing chimeric antigens with a stress protein‐capturing, viral J‐domain
Author(s) -
Schirmbeck Reinhold,
Kwissa Marcin,
Fissolo Nicolas,
Elkholy Shereen,
Riedl Petra,
Reimann Jörg
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0993fje
Subject(s) - immunogenicity , antigen , fusion protein , biology , dna vaccination , ctl* , priming (agriculture) , microbiology and biotechnology , immune system , virology , recombinant dna , gene , immunology , genetics , immunization , germination , botany , cd8
The N‐terminal domain of large tumor antigens (T‐Ag) of polyomaviruses forms a DnaJ‐like structure with a conserved J domain that associates with constitutively expressed stress protein heat shock protein (hsp)73. Mutant (but not wild‐type) SV40 T‐Ag show stable, ATP‐dependent binding to the stress protein hsp73 when expressed in cells from different vertebrate tissues. Intracellular T/hsp73 complexes accumulate to high steady‐state levels. From this observation, we designed a vector system that supports stable expression of a large variety of hsp73capturing, chimeric antigens containing an N‐terminal, T‐Ag‐derived domain, and different C‐terminal antigenic domains from unrelated antigens. Most antigenic domains tested could be stably expressed only in eukaryotic cells as fusion protein/hsp73 complexes. The N‐terminal 77 residues representing the J domain of T‐Ag were required for stable hsp73 binding and efficient expression of chimeric antigens. Hsp73‐bound chimeric antigens expressed by DNA vaccines showed strikingly enhanced immunogenicity evident in humoral (antibody) and cellular cytolytic T lymphocytes (CTL) responses. The described system supports efficient expression of chimeric, polyvalent antigens and their codelivery with hsp73 as a “natural adjuvant” for enhanced immunogenicity for T and B cells.