Gene immunization may induce secondary antibodies reacting with DNA.
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).
Isaguliants
Maria G
MG
Swedish Istitute for Ifectious Disease Control and Microbiology and Tumour Biology Center, Karolinska Institute, Solna, Sweden. isaguliants@hotmail.com
Iakimtchouk
Konstantin
K
Petrakova
Natalia V
NV
Yermalovich
Marina A
MA
Zuber
Anne Kjerrström
AK
Kashuba
Vladimir I
VI
Belikov
Sergey V
SV
Andersson
Sören
S
Kochetkov
Sergey N
SN
Klinman
Dennis M
DM
Wahren
Britta
B
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*
D001323:Autoantibodies; D004277:DNA, Single-Stranded; D018936:Hepatitis C Antigens; D007136:Immunoglobulins; D019444:Vaccines, DNA; D004247:DNA; D054303:HIV Reverse Transcriptase