Effect on antibody and T-cell responses of mixing five GMP-produced DNA plasmids and administration with plasmid expressing GM-CSF

Details

Serval ID
serval:BIB_32641F8662E6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Effect on antibody and T-cell responses of mixing five GMP-produced DNA plasmids and administration with plasmid expressing GM-CSF
Journal
Genes Immun
Author(s)
Sedegah  M., Charoenvit  Y., Aguiar  J., Sacci  J., Hedstrom  R., Kumar  S., Belmonte  A., Lanar  D. E., Jones  T. R., Abot  E., Druilhe  P., Corradin  G., Epstein  J. E., Richie  T. L., Carucci  D. J., Hoffman  S. L.
ISSN
1466-4879 (Print)
Publication state
Published
Issued date
11/2004
Volume
5
Number
7
Pages
553-61
Notes
Comparative Study
Journal Article
Research Support, U.S. Gov't, Non-P.H.S. --- Old month value: Nov
Abstract
One potential benefit of DNA vaccines is the capacity to elicit antibody and T-cell responses against multiple antigens at the same time by mixing plasmids expressing different proteins. A possible negative effect of such mixing is interference among plasmids regarding immunogenicity. In preparation for a clinical trial, we assessed the immunogenicity of GMP-produced plasmids encoding five Plasmodium falciparum proteins, PfCSP, PfSSP2, PfEXP1, PfLSA1, and PfLSA3, given as a mixture, or alone. The mixture induced higher levels of antibodies against whole parasites than did the individual plasmids, but was associated with a decrease in antibodies to individual P. falciparum proteins. T-cell responses were in general decreased by administration of the mixture. Immune responses to individual plasmids and mixtures were generally higher in inbred mice than in outbreds. In inbred BALB/c and C57BL/6 mice, coadministration of a plasmid expressing murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), increased antibody and T-cell responses, but in outbred CD-1 mice, coadministration of mGM-CSF was associated with a decrease in antibody responses. Such variability in data from studies in different strains of mice underscores the importance of genetic background on immune response and carefully considering the goals of any preclinical studies of vaccine mixtures planned for human trials.
Keywords
Animals Antibodies, Protozoan/*biosynthesis Female Granulocyte-Macrophage Colony-Stimulating Factor/*administration & dosage/biosynthesis/genetics Mice Mice, Inbred BALB C Mice, Inbred C57BL Plasmids/*administration & dosage/chemical synthesis/immunology Plasmodium falciparum/*immunology Protein Engineering/methods/*standards Protozoan Vaccines/administration & dosage/genetics/immunology T-Lymphocytes/*drug effects/immunology Vaccines, DNA/*administration & dosage/immunology
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 14:55
Last modification date
20/08/2019 13:18
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