title: Gene immunization may induce secondary antibodies reacting with DNA.
abstract: The fear of autoimmunity in DNA-vaccine recipients initiated screening for anti-DNA antibodies in rabbits immunized with genes of viral nucleic acid-binding and adapter proteins. Of 11 DNA/protein-immunized rabbits, seven had developed secondary antibodies against DNA detected at weeks 11-50 from the on-start of immunization. Two rabbits immunized with HIV-1 reverse transcriptase gene developed transient anti-double-stranded DNA antibodies of high avidity that recognized DNA in the kinetoplasts of Crithidia luciliae. Others developed antibodies reacting with DNA in ELISA and targeting nuclear-associated antigens in the immunofluoresence test. No anti-DNA antibodies were detected at these time-points in any of the controls (P=0.036). Induction of anti-DNA antibodies by epitope spreading from protein domains involved in nucleic acid-binding versus maturation of anti-protein antibodies to dual protein-DNA specificity is discussed. (126 words).
authors.affiliation: Swedish Istitute for Ifectious Disease Control and Microbiology and Tumour Biology Center, Karolinska Institute, Solna, Sweden. isaguliants@hotmail.com
authors.forename: Maria G
authors.initials: MG
authors.lastname: Isaguliants
authors.forename: Konstantin
authors.initials: K
authors.lastname: Iakimtchouk
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Petrakova
authors.forename: Marina A
authors.initials: MA
authors.lastname: Yermalovich
authors.forename: Anne Kjerrström
authors.initials: AK
authors.lastname: Zuber
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Kashuba
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Belikov
authors.forename: Sören
authors.initials: S
authors.lastname: Andersson
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Kochetkov
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002682:Chinchilla; D003421:Crithidia / Q000276:immunology; D004247:DNA / Q000276:immunology*; D004277:DNA, Single-Stranded / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D005814:Genes, Viral / Q000276:immunology; D015754:Genes, nef / Q000235:genetics / Q000276:immunology; D054303:HIV Reverse Transcriptase / Q000235:genetics / Q000276:immunology; D018936:Hepatitis C Antigens / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D019444:Vaccines, DNA / Q000009:adverse effects*
chemical_list: D001323:Autoantibodies; D004277:DNA, Single-Stranded; D018936:Hepatitis C Antigens; D007136:Immunoglobulins; D019444:Vaccines, DNA; D004247:DNA; D054303:HIV Reverse Transcriptase