DNA-based immunization against the envelope proteins of the hepatitis B virus.
Intramuscular injection in mice of DNA expression vectors encoding the envelope proteins of the hepatitis B virus induced humoral responses specific to several antigenic determinants of the viral envelope. The use of different promoter elements in the plasmid vectors influenced the kinetics and specificity of antibodies produced to the envelope proteins. The first antibodies appeared within 1-2 weeks after injection of DNA and included antibodies of the IgM isotype. Over the following weeks, an IgM-to-IgG class switch occurred, indicating helper T-lymphocyte activity. Peak IgG titers were reached by 4 weeks after a single DNA injection and were maintained for at least 6 months without further DNA injections. The antibodies to the envelope proteins reacted with both group- and subtype-specific antigenic determinants of the HBV surface antigen (HBsAg). The nature of the immune response to the envelope proteins provides indirect evidence that the proteins have adopted a native conformation and have probably been assembled into particles after intramuscular expression from the plasmid vectors. These results indicate that it may be possible to rationally design DNA expression vectors to induce a particular type of immune response for vaccination against hepatitis B or other pathogens.
Mancini
M
M
Unité de Recombinaison et Expression Génétique, INSERM U 163, Institut Pasteur, Paris, France.
Davis
H
H
Tiollais
P
P
Michel
M L
ML
D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D004279:DNA, Viral / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000096:biosynthesis* / Q000276:immunology*; D015316:Genetic Therapy; D006510:Hepatitis B Antibodies / Q000096:biosynthesis* / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis* / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood; D007273:Injections, Intramuscular; D007739:L Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014162:Transfection
D004279:DNA, Viral; D015686:Gene Products, env; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M