Reduced immunogenicity of DNA vaccine plasmids in mixtures

• Published in: Gene therapy Vol. 11; no. 5; pp. 448 - 456
• Main Authors: SEDEGAH, M, CHAROENVIT, Y, NARUM, D. L, CARUCCI, D. J, ROGERS, W. O, MINH, L, BELMONTE, M, MAJAM, V. F, ABOT, S, GANESHAN, H, KUMAR, S, BACON, D. J, STOWERS, A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-03-2004
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antibodies, Protozoan - biosynthesis; Antibody response; Antigens; Antigens, Protozoan - administration & dosage; Antigens, Protozoan - immunology; Applied cell therapy and gene therapy; Biological and medical sciences; Biotechnology; Deoxyribonucleic acid; DNA; DNA vaccines; DNA, Protozoan - administration & dosage; Dose-Response Relationship, Immunologic; Female; Fundamental and applied biological sciences. Psychology; Gene therapy; Health. Pharmaceutical industry; Immune Tolerance; Immunization - methods; Immunogenicity; Immunosuppression; Industrial applications and implications. Economical aspects; Interferon-gamma - biosynthesis; Malaria; Malaria Vaccines - administration & dosage; Malaria Vaccines - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Plasmids; Plasmids - immunology; Plasmodium falciparum - immunology; T-Lymphocytes, Cytotoxic - immunology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Vaccines; Vaccines, Combined - immunology; Vaccines, DNA - immunology; γ-Interferon; Plasmid; DNA vaccine; Protozoa; Plasmodium falciparum; Apicomplexa; Immunogenicity; multivalent vaccine; Gene therapy; Genetic vaccine
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3302139

We measured the ability of nine DNA vaccine plasmids encoding candidate malaria vaccine antigens to induce antibodies and interferon-gamma responses when delivered alone or in a mixture containing all nine plasmids. We further examined the possible immunosuppressive effect of individual plasmids, by assessing a series of mixtures in which each of the nine vaccine plasmids was replaced with a control plasmid. Given alone, each of the vaccine plasmids induced significant antibody titers and, in the four cases for which appropriate assays were available, IFN-gamma responses. Significant suppression or complete abrogation of responses were seen when the plasmids were pooled in a nine-plasmid cocktail and injected in a single site. Removal of single genes from the mixture frequently reduced the observed suppression. Boosting with recombinant poxvirus increased the antibody response in animals primed with either a single gene or the mixture, but, even after boosting, responses were higher in animals primed with single plasmids than in those primed with the nine-plasmid mixture. Boosting did not overcome the suppressive effect of mixing for IFN-gamma responses. Interactions between components in a multiplasmid DNA vaccine may limit the ability to use plasmid pools alone to induce responses against multiple targets simultaneously.