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- Title
Reduced immunogenicity of DNA vaccine plasmids in mixtures.
- Authors
Sedegah, M.; Charoenvit, Y.; Minh, L.; Belmonte, M.; Majam, V. F.; Abot, S.; Ganeshan, H.; Kumar, S.; Bacon, D. J.; Stowers, A.; Narum, D. L.; Carucci, D. J.; Rogers, W. O.
- Abstract
We measured the ability of nine DNA vaccine plasmids encoding candidate malaria vaccine antigens to induce antibodies and interferon-? 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-? 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-? 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.Gene Therapy (2004) 11, 448-456. doi:10.1038/sj.gt.3302139
- Subjects
DNA vaccines; MALARIA; PLASMIDS; GENES; PLASMODIUM falciparum; IMMUNOGLOBULINS; VACCINATION
- Publication
Gene Therapy, 2004, Vol 11, Issue 5, p448
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302139