Effect on antibody and T-cell responses of mixing five GMP-produced DNA plasmids and administration with plasmid expressing GM-CSF.
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.
1Malaria Program, Naval Medical Research Center, Silver Spring, MD, USA.
M
M
Sedegah
Y
Y
Charoenvit
J
J
Aguiar
J
J
Sacci
R
R
Hedstrom
S
S
Kumar
A
A
Belmonte
D E
DE
Lanar
T R
TR
Jones
E
E
Abot
P
P
Druilhe
G
G
Corradin
J E
JE
Epstein
T L
TL
Richie
D J
DJ
Carucci
S L
SL
Hoffman
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015202:Protein Engineering / Q000379:methods / Q000592:standards*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D000913:Antibodies, Protozoan; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor